diff --git a/translation/RDB_ETL/pkddi-amy-latest-08152016.csv b/translation/RDB_ETL/pkddi-amy-latest-08152016.csv index 7820d52..910418b 100644 --- a/translation/RDB_ETL/pkddi-amy-latest-08152016.csv +++ b/translation/RDB_ETL/pkddi-amy-latest-08152016.csv @@ -1,337 +1,337 @@ -"source","date","assertionType","evidenceType","exactText","modality","statementType","comment","drug1Lab","drug1Type","drug1Role","dose1","drug2Lab","drug2Type","drug2Role","dose2","objectRegimens","objectFormulation","objectDuration","preciptRegimens","preciptFormulation","preciptDuration","numOfParticipants","auc","aucType","aucDirection","cl","clType","clDirection","cmax","cmaxType","cmaxDirection","t12","t12Type","t12Direction" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 17:58:31 -0700","DDI-clinical-trial","evidence-supports","Promethazine: Coadministration of a single dose of zaleplon and promethazine (10 and 25 mg, respectively) resulted in a 15% decrease in maximal plasma concentrations of zaleplon, but no change in the area under the plasma concentration-time curve. However, the pharmacodynamics of coadministration of zaleplon and promethazine have not been evaluated. Caution should be exercised when these 2 agents are coadministered.","ncit:positive","ncit:quantitative","but no change in the area under the plasma concentration-time curve.","promethazine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","25","zaleplon","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","10","SD","Oral","1","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","15","Percent","Decrease","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1a5a93be-7bc3-4714-9308-2fbfb8260e23.html","2016-02-29 15:03:48 -0700","drug-drug-interaction","evidence-supports","Concomitant administration of propranolol with phenothiazines results in increased plasma levels of both drugs.","ncit:positive","ncit:Qualitative","Concomitant administration of propranolol with phenothiazines results in increased plasma levels of both drugs","propranolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"phenothiazines","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 14:55:51 -0700","drug-drug-interaction","evidence-supports","The concomitant use of PRADAXA with P-gp inducers (e.g., rifampin) reduces exposure to dabigatran and should generally be avoided [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative","rifampin reduces exposure to dabigatran","dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","rifampin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 22:55:21 -0400","drug-drug-interaction","evidence-challenges","Zolpidem tartrate had no effect on digoxin pharmacokinetics and did not affect prothrombin time when given with warfarin in healthy subjects.","ncit:negative","ncit:Qualitative","did not affect prothrombin time when given with warfarin","Zolpidem","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 10:48:58 -0700","drug-drug-interaction","evidence-supports","Avoid concomitant use of ELIQUIS with strong dual inducers of CYP3A4 and P-gp (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort) because such drugs will decrease exposure to apixaban [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative","rifampin will decrease exposure to apixaban","rifampin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"apixaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ee49f3b1-1650-47ff-9fb1-ea53fe0b92b6.html","2016-03-14 14:01:17 -0700","DDI-clinical-trial","evidence-supports","The effects of ABILIFY on the exposures of other drugs are summarized in Figure 21. A population PK analysis in patients with major depressive disorder showed no substantial change in plasma concentrations of fluoxetine (20 mg/day or 40 mg/day), paroxetine CR (37.5 mg/day or 50 mg/day), or sertraline (100 mg/day or 150 mg/day) dosed to steady-state. The steady-state plasma concentrations of fluoxetine and norfluoxetine increased by about 18% and 36%, respectively, and concentrations of paroxetine decreased by about 27%. The steady-state plasma concentrations of sertraline and desmethylsertraline were not substantially changed when these antidepressant therapies were coadministered with aripiprazole.","ncit:positive","ncit:quantitative","this was a pop pk study","ABILIFY","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","norfluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","20-40","Daily","Oral","UNK","UNK","UNK","UNK","UNK","36","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 15:06:41 -0700","DDI-clinical-trial","evidence-supports","Ketoconazole: Systemic ketoconazole increased dabigatran AUC and Cmax values by 138% and 135%, respectively, after a single dose of 400 mg, and 153%, and 149%, respectively, after multiple daily doses of 400 mg.","ncit:positive","ncit:quantitative",,"ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","400","dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","SD","Oral","1","UNK","138","Percent","Increase","UNK","UNK","UNK","135","Percent","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:26:31 -0700","drug-drug-interaction","evidence-supports","In drug interaction studies evaluating the concomitant use with drugs that are combined P-gp and CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin, erythromycin and fluconazole), increases in rivaroxaban exposure and pharmacodynamic effects (i.e., factor Xa inhibition and PT prolongation) were observed. The increases in exposure ranged from 30% to 160%. Significant increases in rivaroxaban exposure may increase bleeding risk [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative","increases in rivaroxaban exposure","rivaroxaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","ritonavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 13:01:39 -0800","DDI-clinical-trial","evidence-supports","When a single oral 0.25 mg dose of triazolam was coadministered with nefazodone (200 mg BID) at steady state, triazolam half-life and AUC increased 4 fold and peak concentrations increased 1.7 fold. ","ncit:positive","ncit:quantitative",,"nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","triazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction",".25","SD","Oral","1","BID","Oral","UNK","UNK","4","Fold","Increase","UNK","UNK","UNK","1.7","Fold","Increase","4","Fold","Increase" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/39a5dae2-49f7-4662-9eac-aa7b4c7807a4.html","2016-05-09 19:41:26 -0400","DDI-clinical-trial","evidence-challenges","Warfarin: Eszopiclone 3 mg administered daily for 5 days did not affect the pharmacokinetics of (R)- or (S)-warfarin, nor were there any changes in the pharmacodynamic profile (prothrombin time) following a single 25 mg oral dose of warfarin. ","ncit:negative","ncit:quantitative","Eszopiclone 3 mg administered daily for 5 days did not affect the pharmacokinetics of warfarin","Eszopiclone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","3","warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","25","SD","Oral","1","Daily","Oral","5","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 16:13:29 -0700","drug-drug-interaction","evidence-supports","Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin. (See CONTRAINDICATIONS, WARNINGS, Myopathy/Rhabdomyolysis, and CLINICAL PHARMACOLOGY, Pharmacokinetics.)","ncit:positive","ncit:Qualitative","Clarithromycin is a strong inhibitor of CYP3A4 and reduces the elimination of lovastatin","clarithromycin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"lovastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-30 15:09:14 -0700","drug-drug-interaction","evidence-supports","Concomitant administration of fluvastatin and phenytoin increased phenytoin exposures. Patients should continue to be monitored appropriately when fluvastatin therapy is initiated or when fluvastatin dose is changed [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative","Concomitant fluvastatin increases phenytoin exposure. Details in Section 12 Table 3","phenytoin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2015-11-29 14:35:23 -0700","DDI-clinical-trial","evidence-supports","Ketoconazole: Co-administration of ketoconazole (200 mg twice daily for 4 days), a potent inhibitor of CYP3A4, with a 3 mg single dose of iloperidone to 19 healthy volunteers, ages 18 to 45 years, increased the area under the curve (AUC) of iloperidone and its metabolites P88 and P95 by 57%, 55% and 35%, respectively. Iloperidone doses should be reduced by about one-half when administered with ketoconazole or other strong inhibitors of CYP3A4 (e.g., itraconazole). Weaker inhibitors (e.g., erythromycin, grapefruit juice) have not been studied. When the CYP3A4 inhibitor is withdrawn from the combination therapy, the iloperidone dose should be returned to the previous level.","ncit:positive","ncit:quantitative",,"ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","iloperidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","3","SD","Oral","1","BID","Oral","4","19","57","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d78e9639-6fab-4a78-8b29-6991a18ae6c6.html","2016-02-19 17:46:51 -0500","drug-drug-interaction","evidence-supports","In one study of 45 elderly patients suffering from dementia treated with perphenazine, the 5 patients who were prospectively identified as poor P450 2D6 metabolizers had reported significantly greater side effects during the first 10 days of treatment than the 40 extensive metabolizers, following which the groups tended to converge. Prospective phenotyping of elderly patients prior to antipsychotic treatment may identify those at risk for adverse events. The concomitant administration of other drugs that inhibit the activity of P450 2D6 may acutely increase plasma concentrations of antipsychotics. Among these are tricyclic antidepressants and selective serotonin reuptake inhibitors, e.g., fluoxetine, sertraline and paroxetine. When prescribing these drugs to patients already receiving antipsychotic therapy, close monitoring is essential and dose reduction may become necessary to avoid toxicity. Lower doses than usually prescribed for either the antipsychotic or the other drug may be required.","ncit:positive","ncit:Qualitative","may acutely increase plasma concentrations of antipsychotics.","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"perphenazine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-31 12:56:52 -0700","drug-drug-interaction","evidence-challenges","Data from drug-drug interactions studies involving coadministration of gemfibrozil, niacin, itraconazole, erythromycin, tolbutamide or clopidogrel indicate that the PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with any of these drugs.","ncit:negative","ncit:Qualitative","PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with tolbutamide","tolbutamide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"fluvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/9c4bedb4-2d59-4fcd-aad7-fce988cd96d8.html","2016-02-29 14:37:32 -0700","DDI-clinical-trial","evidence-supports","The effect of fluvoxamine (25 mg b.i.d. for one week) on thioridazine steady-state concentration was evaluated in ten male inpatients with schizophrenia. Concentrations of thioridazine and its two active metabolites, mesoridazine and sulforidazine, increased 3-fold following coadministration of fluvoxamine. Fluvoxamine and thioridazine should not be coadministered.","ncit:positive","ncit:quantitative",,"sulforidazine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","UNK","Fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","25","UNK","Oral","UNK","BID","Oral","7","10","3","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2015-11-29 15:12:19 -0700","DDI-clinical-trial","evidence-supports","Dextromethorphan: A study in healthy volunteers showed that changes in the pharmacokinetics of dextromethorphan (80 mg dose) when a 3 mg dose of iloperidone was co-administered resulted in a 17% increase in total exposure and a 26% increase in the maximum plasma concentrations (Cmax)of dextromethorphan. Thus, an interaction between iloperidone and other CYP2D6 substrates is unlikely.","ncit:positive","ncit:quantitative",,"dextromethorphan","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","80","iloperidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","3","SD","Oral","1","SD","Oral","1","UNK","17","Percent","Increase","UNK","UNK","UNK","26","Percent","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 10:37:19 -0800","DDI-clinical-trial","evidence-challenges","Phenytoin – Pretreatment for 7 days with 200 mg BID of nefazodone had no effect on the pharmacokinetics of a single 300 mg oral dose of phenytoin. However, due to the nonlinear pharmacokinetics of phenytoin, the failure to observe a significant effect on the single-dose pharmacokinetics of phenytoin does not preclude the possibility of a clinically significant interaction with nefazodone when phenytoin is dosed chronically. ","ncit:negative","ncit:quantitative",,"nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","Phenytoin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","300","SD","Oral","1","BID","Oral","7","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-02-18 16:49:30 -0700","DDI-clinical-trial","evidence-supports","A pharmacokinetic study was conducted in 16 schizophrenic patients who received clozapine under steady-state conditions. After coadministration of fluvoxamine for 14 days, mean trough concentrations of clozapine and its metabolites, N-desmethylclozapine and clozapine N-oxide, were elevated about 3-fold compared to baseline steady-state concentrations.","ncit:positive","ncit:quantitative",,"clozapine N-oxide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","UNK","fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","14","16","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/827cf470-485d-4925-85f2-8933a6dea830.html","2016-03-14 17:27:36 -0400","drug-drug-interaction","evidence-supports","Hepatic microsomal enzyme inducing agents, such as carbamazepine, were found to significantly increase the clearance of thiothixene. Patients receiving these drugs should be observed for signs of reduced thiothixene effectiveness4,5.","ncit:positive","ncit:Qualitative","carbemazepine found to significantly increase the clearance of thiothixene","carbamazepine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"thiothixene","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 13:29:38 -0800","DDI-clinical-trial","evidence-challenges","Lorazepam – When lorazepam (2 mg BID) and nefazodone (200 mg BID) were coadministered to steady state, there was no change in any pharmacokinetic parameter for either drug compared to each drug administered alone. Therefore, dosage adjustment is not necessary for either drug when coadministered.","ncit:negative","ncit:quantitative",,"Lorazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","5","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","SD","Oral","1","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e1e5249-1cb7-4cc2-ad5a-cdeeee2f494f.html","2016-02-16 16:34:55 -0700","drug-drug-interaction","evidence-supports","Quetiapine exposure is increased by the prototype CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.)","ncit:positive","ncit:Qualitative","quetiapine exposure is increased by CYP3A4 inhibitors","indinavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"Quetiapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-31 12:56:20 -0700","drug-drug-interaction","evidence-challenges","Data from drug-drug interactions studies involving coadministration of gemfibrozil, niacin, itraconazole, erythromycin, tolbutamide or clopidogrel indicate that the PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with any of these drugs.","ncit:negative","ncit:Qualitative","PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with erythromycin","erythromycin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"fluvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4b0700c9-b417-4c3a-b36f-de461e125bd3.html","2015-11-29 13:52:49 -0700","DDI-clinical-trial","evidence-challenges","Coadministration of aspirin 150 mg/day with multiple daily doses of BRINTELLIX had no significant inhibitory effect on platelet aggregation or pharmacokinetics of aspirin and salicylic acid [see Drug Interactions (7.4)].","ncit:negative","ncit:quantitative",,"salicylic acid","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","150","BRINTELLIX","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","Daily","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNKUNUNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 16:16:27 -0700","drug-drug-interaction","evidence-supports","Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin. (See CONTRAINDICATIONS, WARNINGS, Myopathy/Rhabdomyolysis, and CLINICAL PHARMACOLOGY, Pharmacokinetics.)","ncit:positive","ncit:Qualitative","Nefazodone is a strong inhibitor of CYP3A4 and reduces the elimination of lovastatin","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"lovastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 16:06:57 -0700","drug-drug-interaction","evidence-challenges","In clinical studies exploring CYP3A4, CYP2C9, P-gp and other pathways, dabigatran did not meaningfully alter the pharmacokinetics of amiodarone, atorvastatin, clarithromycin, diclofenac, clopidogrel, digoxin, pantoprazole, or ranitidine.","ncit:negative","ncit:Qualitative","dabigatran did not meaningfully alter the pharmacokinetics of clopidogrel","dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"clopidogrel","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-31 12:55:51 -0700","drug-drug-interaction","evidence-challenges","Data from drug-drug interactions studies involving coadministration of gemfibrozil, niacin, itraconazole, erythromycin, tolbutamide or clopidogrel indicate that the PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with any of these drugs.","ncit:negative","ncit:Qualitative","PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with itraconazole","itraconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"fluvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 18:14:59 -0700","DDI-clinical-trial","evidence-challenges","Digoxin: Zaleplon (10 mg) did not affect the pharmacokinetic or pharmacodynamic profile of digoxin (0.375 mg q24h for 8 days).","ncit:negative","ncit:quantitative","Zaleplon did not affect the pharmacokinetic s of digoxin","Zaleplon","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","10","digoxin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction",".375","QD","Oral","8","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/afad3051-9df2-4c54-9684-e8262a133af8.html","2015-12-08 19:35:35 -0700","DDI-clinical-trial","evidence-challenges","Valproate: It is not necessary to adjust the LATUDA dose when used concomitantly with valproate. A dedicated drug-drug interaction study has not been conducted with valproate and LATUDA. Based on pharmacokinetic data from the bipolar depression studies valproate levels were not affected by lurasidone, and lurasidone concentrations were not affected by valproate. ","ncit:negative","ncit:quantitative",,"lurasidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","valproate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 16:02:33 -0700","drug-drug-interaction","evidence-challenges","Oral Hypoglycemic Agents: In pharmacokinetic studies of MEVACOR in hypercholesterolemic non-insulin dependent diabetic patients, there was no drug interaction with glipizide or with chlorpropamide (see CLINICAL PHARMACOLOGY, Clinical Studies).","ncit:negative","ncit:Qualitative","There was no drug interaction with concomitant lovastatin and chlorpropamide (see CLINICAL PHARMACOLOGY, Clinical Studies)","MEVACOR","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"chlorpropamide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 13:11:00 -0800","DDI-clinical-trial","evidence-supports","When alprazolam (1 mg BID) and nefazodone (200 mg BID) were coadministered, steady-state peak concentrations, AUC and half-life values for alprazolam increased by approximately 2 fold.","ncit:positive","ncit:quantitative",,"nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","alprazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","1","BID","Oral","UNK","BID","Oral","UNK","UNK","2","Fold","Increase","UNK","UNK","UNK","2","Fold","Increase","2","Fold","Increase" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1a5a93be-7bc3-4714-9308-2fbfb8260e23.html","2016-02-29 17:07:32 -0500","drug-drug-interaction","evidence-supports","Concomitant administration of propranolol with phenothiazines results in increased plasma levels of both drugs.","ncit:positive","ncit:Qualitative","Concomitant administration of propranolol with phenothiazines results in increased plasma levels of both drugs","phenothiazines","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"propranolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 16:00:52 -0700","drug-drug-interaction","evidence-challenges","Oral Hypoglycemic Agents: In pharmacokinetic studies of MEVACOR in hypercholesterolemic non-insulin dependent diabetic patients, there was no drug interaction with glipizide or with chlorpropamide (see CLINICAL PHARMACOLOGY, Clinical Studies).","ncit:negative","ncit:Qualitative","There was no drug interaction with concomitant lovastatin and glipizide or with chlorpropamide (see CLINICAL PHARMACOLOGY, Clinical Studies).","MEVACOR","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"glipizide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/9c4bedb4-2d59-4fcd-aad7-fce988cd96d8.html","2016-02-29 14:19:31 -0700","drug-drug-interaction","evidence-supports","Reduced cytochrome P450 2D6 isozyme activity drugs that inhibit this isozyme (e.g., fluoxetine and paroxetine) and certain other drugs (e.g., fluvoxamine, propranolol, and pindolol) appear to appreciably inhibit the metabolism of thioridazine. The resulting elevated levels of thioridazine would be expected to augment the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as Torsades de pointes type arrhythmias.","ncit:positive","ncit:Qualitative","appear to appreciably inhibit the metabolism of thioridazine and result in elevated levels of thioridazine","thioridazine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/7d1a9689-23c8-44ef-a474-8c607e13d794.html","2016-03-14 15:46:58 -0400","drug-drug-interaction","evidence-supports","In 5 other schizophrenic patients treated with haloperidol and rifampin, discontinuation of rifampin produced a mean 3.3-fold increase in haloperidol concentrations. Thus, careful monitoring of clinical status is warranted when rifampin is administered or discontinued in haloperidol-treated patients.","ncit:positive","ncit:Qualitative","iscontinuation of rifampin produced a mean 3.3-fold increase in haloperidol concentrations.","haloperidol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","rifampin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 14:04:35 -0800","DDI-clinical-trial","evidence-supports","With 5 mg BID doses of buspirone, slight increases in AUC were observed for nefazodone (23%) and its metabolites hydroxynefazodone (17%) and mCPP (9%).","ncit:positive","ncit:quantitative",,"buspirone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","5","hydroxynefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","250","BID","Oral","UNK","BID","Oral","UNK","UNK","17","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 16:06:27 -0700","drug-drug-interaction","evidence-challenges","In clinical studies exploring CYP3A4, CYP2C9, P-gp and other pathways, dabigatran did not meaningfully alter the pharmacokinetics of amiodarone, atorvastatin, clarithromycin, diclofenac, clopidogrel, digoxin, pantoprazole, or ranitidine.","ncit:negative","ncit:Qualitative","dabigatran did not meaningfully alter the diclofenac","diclofenac","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:37:29 -0700","drug-drug-interaction","evidence-supports","Concomitant use of CLOZARIL and CYP1A2 inhibitors can increase plasma levels of clozapine, potentially resulting in adverse reactions. Reduce the CLOZARIL dose to one-third of the original dose when CLOZARIL is coadministered with strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin, or enoxacin). The CLOZARIL dose should be increased to the original dose when coadministration of strong CYP1A2 inhibitors is discontinued [see Dosage and Administration (2.6), Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative","ciprofloxacin can increase clozapine levels","clozapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","ciprofloxacin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 13:28:51 -0700","DDI-clinical-trial","evidence-challenges","Single doses of olanzapine did not affect the pharmacokinetics of imipramine or its active metabolite desipramine.","ncit:negative","ncit:quantitative",,"imipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","olanzapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/309f8ac3-a3fd-4313-96aa-7f21fa9cd646.html","2016-05-10 13:11:45 -0400","DDI-clinical-trial","evidence-challenges","Bupropion (a CYP2B6 substrate): Co-administration of a single dose of 150 mg Bupropion Hydrochloride XL with steady state quazepam did not significantly affect the AUC and Cmax of bupropion or its primary metabolite, hydroxybupropion.","ncit:negative","ncit:quantitative","did not significantly affect the AUC and Cmax of bupropion or its primary metabolite, hydroxybupropion.","quazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","hydroxybupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","150","SD","Oral","1","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 12:34:19 -0700","DDI-clinical-trial","evidence-supports"," Carbamazepine therapy (200 mg bid) causes an approximately 50% increase in the clearance of olanzapine. ","ncit:positive","ncit:quantitative",,"Carbamazepine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","olanzapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","50","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/50914a46-eab6-4c83-97cf-6ab0234c8126.html","2016-05-10 12:55:04 -0400","DDI-clinical-trial","evidence-challenges","A multiple-dose study was conducted to assess the effect of fluoxetine 20 mg BID on the pharmacokinetics of estazolam 2 mg QHS after seven days. The pharmacokinetics of estazolam (Cmax and AUC) were not affected during multiple-dose fluoxetine, suggesting no clinically significant pharmacokinetic interaction.","ncit:negative","ncit:quantitative","pharmacokinetics of estazolam (Cmax and AUC) were not affected","estazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","2","fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","QD","Oral","7","BID","Oral","7","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 13:30:19 -0700","DDI-clinical-trial","evidence-challenges","Single doses of olanzapine did not affect the pharmacokinetics of imipramine or its active metabolite desipramine.","ncit:negative","ncit:quantitative",,"olanzapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","desipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","SD","Oral","1","UNK","UNKUNUNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:37:25 -0700","DDI-clinical-trial","evidence-supports","Ketoconazole (combined P-gp and strong CYP3A4 inhibitor): Steady-state rivaroxaban AUC and Cmax increased by 160% and 70%, respectively. Similar increases in pharmacodynamic effects were also observed.","ncit:positive","ncit:quantitative",,"rivaroxaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","Ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","160","Percent","Increase","UNK","UNK","UNK","70","Percent","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 16:08:16 -0700","drug-drug-interaction","evidence-supports","Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin. (See CONTRAINDICATIONS, WARNINGS, Myopathy/Rhabdomyolysis, and CLINICAL PHARMACOLOGY, Pharmacokinetics.)","ncit:positive","ncit:Qualitative","Ketoconazole is a strong inhibitor of CYP3A4 and reduces the elimination of lovastatin","ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"lovastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 13:26:49 -0800","DDI-clinical-trial","evidence-challenges"," Pharmacodynamic effects of haloperidol were generally not altered significantly. There were no changes in the pharmacokinetic parameters for nefazodone","ncit:negative","ncit:quantitative",,"nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","200","haloperidol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","5","BID","Oral","UNK","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:22:15 -0700","drug-drug-interaction","evidence-supports","Results from drug interaction studies and population PK analyses from clinical studies indicate coadministration of XARELTO with a combined P-gp and strong CYP3A4 inducer (e.g., rifampicin, phenytoin) decreased rivaroxaban exposure by up to 50%.","ncit:positive","ncit:Qualitative","decreased rivaroxaban exposure by up to 50%.","rivaroxaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","phenytoin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/7d1a9689-23c8-44ef-a474-8c607e13d794.html","2016-03-14 15:46:58 -0400","drug-drug-interaction","evidence-supports","In a study of 12 schizophrenic patients coadministered haloperidol and rifampin, plasma haloperidol levels were decreased by a mean of 70% and mean scores on the Brief Psychiatric Rating Scale were increased from baseline.","ncit:positive","ncit:Qualitative","plasma haloperidol levels were decreased by a mean of 70%","haloperidol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","rifampin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/309f8ac3-a3fd-4313-96aa-7f21fa9cd646.html","2016-05-10 10:09:49 -0700","DDI-clinical-trial","evidence-challenges","Bupropion (a CYP2B6 substrate): Co-administration of a single dose of 150 mg Bupropion Hydrochloride XL with steady state quazepam did not significantly affect the AUC and Cmax of bupropion or its primary metabolite, hydroxybupropion.","ncit:negative","ncit:quantitative","did not significantly affect the AUC and Cmax of bupropion","quazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","Bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","150","SD","Oral","1","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/39a5dae2-49f7-4662-9eac-aa7b4c7807a4.html","2016-05-09 16:27:24 -0700","DDI-clinical-trial","evidence-supports","Eszopiclone and lorazepam decreased each other's Cmax by 22%. ","ncit:positive","ncit:quantitative",,"lorazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","Eszopiclone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","22","Percent","Decrease","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 12:20:54 -0800","drug-drug-interaction","evidence-supports","There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. Both cyclosporine and tacrolimus are substrates of CYP3A4, and nefazodone is known to inhibit this enzyme. If either cyclosporine or tacrolimus is administered with nefazodone, blood concentrations of the immunosuppressive agent should be monitored and dosage adjusted accordingly.","ncit:positive","ncit:Qualitative","eports of increased blood concentrations","cyclosporine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 12:14:12 -0800","drug-drug-interaction","evidence-supports","Lithium – In 13 healthy subjects the coadministration of nefazodone (200 mg BID) with lithium (500 mg BID) for 5 days (steady-state conditions) was found to be well tolerated. When the two drugs were coadministered, there were no changes in the steady-state pharmacokinetics of either lithium, nefazodone, or its metabolite HO-NEF; however, there were small decreases in the steady-state plasma concentrations of two nefazodone metabolites, mCPP and triazole-dione, which are considered not to be of clinical significance. Therefore, no dosage adjustment of either lithium or nefazodone is required when they are coadministered.","ncit:positive","ncit:Qualitative","small decreases in the steady-state plasma concentrations which are considered not to be of clinical significance.","mCPP","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","","Lithium","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c6e131fe-e7df-4876-83f7-9156fc4e8228.html","2016-03-14 15:25:58 -0700","DDI-clinical-trial","evidence-supports","Co-administered drug and dosing regimen Atorvastatin Dose (mg) Change in AUC* Change in Cmax* * Data given as x-fold change represent a simple ratio between co-administration and atorvastatin alone (i.e., 1-fold = no change). Data given as % change represent % difference relative to atorvastatin alone (i.e., 0% = no change). † See Sections 5.1 and 7 for clinical significance. ‡ The dose of saquinavir plus ritonavir in this study is not the clinically used dose. The increase in atorvastatin exposure when used clinically is likely to be higher than what was observed in this study. Therefore, caution should be applied and the lowest dose necessary should be used. § Greater increases in AUC (up to 2.5 fold) and/or Cmax (up to 71%) have been reported with excessive grapefruit consumption (≥ 750 mL – 1.2 liters per day). ¶ Single sample taken 8–16 h post dose. # Due to the dual interaction mechanism of rifampin, simultaneous co-administration of atorvastatin with rifampin is recommended, as delayed administration of atorvastatin after administration of rifampin has been associated with a significant reduction in atorvastatin plasma concentrations. †Cyclosporine 5.2 mg/kg/day, stable dose 10 mg QD for 28 days ↑ 8.7 fold ↑ 10.7 fold †Tipranavir 500 mg BID/ritonavir 200 mg BID, 7 days 10 mg, SD ↑ 9.4 fold ↑ 8.6 fold †Telaprevir 750 mg q8h, 10 days 20 mg, SD ↑ 7.88 fold ↑ 10.6 fold","ncit:positive","ncit:quantitative",,"atorvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","10","Telaprevir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","750","SD","Oral","1","Q8","Oral","10","UNK","7.88","Fold","Increase","UNK","UNK","UNK","10.6","Fold","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/49c4105b-e518-481c-a248-6684135f5bc1.html","2015-11-29 18:49:20 -0500","DDI-clinical-trial","evidence-challenges","Risperidone (0.25 mg twice daily) did not show a clinically relevant effect on the pharmacokinetics of digoxin. Dose adjustment for digoxin is not recommended.","ncit:negative","ncit:quantitative",,"digoxin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","Risperidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",".25","UNK","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/39a5dae2-49f7-4662-9eac-aa7b4c7807a4.html","2016-05-09 16:39:00 -0700","drug-drug-interaction","evidence-challenges","Lorazepam: Coadministration of single doses of eszopiclone and lorazepam did not have clinically relevant effects on the pharmacodynamics or pharmacokinetics of either drug. The lack of a drug interaction following single-dose administration does not predict the complete absence of a pharmacodynamic effect following chronic administration. ","ncit:negative","ncit:Qualitative","Coadministration of single doses of eszopiclone and lorazepam did not have clinically relevant effects on the pharmacodynamics or pharmacokinetics of either drug","eszopiclone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","lorazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 12:58:57 -0800","DDI-clinical-trial","evidence-supports","Interaction studies of nefazodone with two triazolobenzodiazepines, i.e., triazolam and alprazolam, metabolized by cytochrome P450 3A4, have revealed substantial and clinically important increases in plasma concentrations of these compounds when administered concomitantly with nefazodone","ncit:positive","ncit:quantitative","ncreases in plasma concentrations","alprazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/fdbfe194-b845-42c5-bb87-a48118bc72e7.html","2016-03-31 15:44:32 -0400","drug-drug-interaction","evidence-supports","In two clinical studies, one in normal volunteers and the other in hypercholesterolemic patients, simvastatin 20-40 mg/day modestly potentiated the effect of coumarin anticoagulants: the prothrombin time, reported as International Normalized Ratio (INR), increased from a baseline of 1.7 to 1.8 and from 2.6 to 3.4 in the volunteer and patient studies, respectively. ","ncit:positive","ncit:Qualitative","simvastatin modestly increased INR from a baseline of 1.7 to 1.8 and from 2.6 to 3.4 in the volunteer and patient studies respectively.","coumarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","simvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 16:08:19 -0700","drug-drug-interaction","evidence-challenges","In clinical studies exploring CYP3A4, CYP2C9, P-gp and other pathways, dabigatran did not meaningfully alter the pharmacokinetics of amiodarone, atorvastatin, clarithromycin, diclofenac, clopidogrel, digoxin, pantoprazole, or ranitidine.","ncit:negative","ncit:Qualitative","dabigatran did not meaningfully alter the pharmacokinetics of pantoprazole","pantoprazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 16:05:56 -0700","drug-drug-interaction","evidence-challenges","In clinical studies exploring CYP3A4, CYP2C9, P-gp and other pathways, dabigatran did not meaningfully alter the pharmacokinetics of amiodarone, atorvastatin, clarithromycin, diclofenac, clopidogrel, digoxin, pantoprazole, or ranitidine.","ncit:negative","ncit:Qualitative","dabigatran did not meaningfully alter the pharmacokinetics of clarithromycin","dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"clarithromycin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 15:26:04 -0700","DDI-clinical-trial","evidence-supports","Verapamil: When dabigatran etexilate was coadministered with oral verapamil, the Cmax and AUC of dabigatran were increased. The extent of increase depends on the formulation of verapamil and timing of administration. If verapamil is present in the gut when dabigatran is taken, it will increase exposure to dabigatran with the greatest increase observed when a single dose of immediate-release verapamil is given one hour prior to dabigatran (AUC increased by a factor of 2.4). If verapamil is given 2 hours after dabigatran, the increase in AUC is negligible.","ncit:positive","ncit:quantitative","The extent of increase depends on the formulation of verapamil and timing of administration. If verapamil is present in the gut when dabigatran is taken, it will increase exposure to dabigatran with the greatest increase observed when a single dose of immediate-release verapamil is given one hour prior to dabigatran (AUC increased by a factor of 2.4). If verapamil is given 2 hours after dabigatran, the increase in AUC is negligible.","dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","verapamil","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","Increase","UNK","UNK","UNK","UNK","UNK","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 14:29:38 -0800","DDI-clinical-trial","evidence-challenges"," When fluoxetine (20 mg QD) and nefazodone (200 mg BID) were administered at steady state there were no changes in the pharmacokinetic parameters for fluoxetine or its metabolite, norfluoxetine. Similarly, there were no changes in the pharmacokinetic parameters of nefazodone or HO-NEF; however, the mean AUC levels of the nefazodone metabolites mCPP and triazole-dione increased by 3 to 6 fold and 1.3 fold, respectively","ncit:negative","ncit:quantitative",,"HO-NEF","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","200","fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","BID","Oral","UNK","QD","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e1e5249-1cb7-4cc2-ad5a-cdeeee2f494f.html","2016-02-16 16:45:41 -0700","drug-drug-interaction","evidence-supports","Quetiapine exposure is increased by the prototype CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.). and decreased by the prototype CYP3A4 inducers (e..g, phenytoin, carbamazepine, rifampin, avasimibe, St. John’s wort etc.).","ncit:positive","ncit:Qualitative","quetiapine exposure is decreased by CYP3A4 inducers","carbamazepine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"Quetiapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/036db1f2-52b3-42a0-acf9-817b7ba8c724.html","2015-12-08 18:52:09 -0700","DDI-clinical-trial","evidence-challenges","Ziprasidone at a dose of 40 mg twice daily administered concomitantly with lithium at a dose of 450 mg twice daily for 7 days did not affect the steady-state level or renal clearance of lithium. Ziprasidone dosed adjunctively to lithium in a maintenance trial of bipolar patients did not affect mean therapeutic lithium levels.","ncit:negative","ncit:quantitative",,"Ziprasidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","lithium","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","450","BID","Oral","7","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 12:22:19 -0800","drug-drug-interaction","evidence-supports","There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. Both cyclosporine and tacrolimus are substrates of CYP3A4, and nefazodone is known to inhibit this enzyme. If either cyclosporine or tacrolimus is administered with nefazodone, blood concentrations of the immunosuppressive agent should be monitored and dosage adjusted accordingly.","ncit:positive","ncit:Qualitative","eports of increased blood concentrations","tacrolimus","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/fdbfe194-b845-42c5-bb87-a48118bc72e7.html","2016-03-31 12:22:57 -0700","drug-drug-interaction","evidence-supports","Elevated plasma levels of HMG-CoA reductase inhibitory activity increases the risk of myopathy and rhabdomyolysis, particularly with higher doses of simvastatin. [See Warnings and Precautions (5.1) and Clinical Pharmacology (12.3).] Concomitant use of drugs labeled as having a strong inhibitory effect on CYP3A4 is contraindicated [see Contraindications (4)]. If treatment with itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with simvastatin must be suspended during the course of treatment.","ncit:positive","ncit:Qualitative","strong inhibitor of CYP3A4 may elevate simvastatin plasma level","simvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","voriconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e1e5249-1cb7-4cc2-ad5a-cdeeee2f494f.html","2016-02-16 16:34:30 -0700","drug-drug-interaction","evidence-supports","Quetiapine exposure is increased by the prototype CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.)","ncit:positive","ncit:Qualitative","quetiapine exposure is increased by CYP3A4 inhibitors","itraconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"Quetiapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e1e5249-1cb7-4cc2-ad5a-cdeeee2f494f.html","2016-02-16 16:45:41 -0700","drug-drug-interaction","evidence-supports","Quetiapine exposure is increased by the prototype CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.). and decreased by the prototype CYP3A4 inducers (e..g, phenytoin, carbamazepine, rifampin, avasimibe, St. John’s wort etc.).","ncit:positive","ncit:Qualitative","quetiapine exposure is decreased by CYP3A4 inducers","Quetiapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","avasimibe","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c6e131fe-e7df-4876-83f7-9156fc4e8228.html","2016-03-14 15:11:38 -0700","drug-drug-interaction","evidence-supports","Co-administration of LIPITOR and an oral contraceptive increased AUC values for norethindrone and ethinyl estradiol [see Clinical Pharmacology (12.3)]. These increases should be considered when selecting an oral contraceptive for a woman taking LIPITOR","ncit:positive","ncit:Qualitative","Co-administration of LIPITOR and an oral contraceptive increased AUC values for norethindrone and ethinyl estradiol","LIPITOR","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"ethinyl estradiol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:43:26 -0700","drug-drug-interaction","evidence-supports","Concomitant treatment with CLOZARIL and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology (12.3)]. Use caution and monitor patients closely when using such inhibitors. Consider reducing the CLOZARIL dose [see Dosage and Administration (2.6)]","ncit:positive","ncit:Qualitative","Sertraline can increase clozapine levels","sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"clozapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 17:36:33 -0700","drug-drug-interaction","evidence-challenges"," In a single-dose drug interaction study there were no pharmacokinetic or pharmacodynamic interactions observed after concomitant administration of naproxen or aspirin (acetylsalicylic acid) with XARELTO.","ncit:negative","ncit:Qualitative","no pharmacokinetic or pharmacodynamic interactions observed after concomitant administration of naproxen or aspirin (acetylsalicylic acid) with XARELTO.","XARELTO","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","aspirin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:41:56 -0700","drug-drug-interaction","evidence-supports","Concomitant treatment with CLOZARIL and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology (12.3)]. Use caution and monitor patients closely when using such inhibitors. Consider reducing the CLOZARIL dose [see Dosage and Administration (2.6)]","ncit:positive","ncit:Qualitative","Fluoxetine can increase clozapine levels","clozapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e1e5249-1cb7-4cc2-ad5a-cdeeee2f494f.html","2016-02-16 16:50:39 -0700","drug-drug-interaction","evidence-supports","Coadministration of ketoconazole, a potent inhibitor of cytochrome CYP3A4, resulted in significant increase in quetiapine exposure.","ncit:positive","ncit:Qualitative","significantly increased quetiapine exposure","quetiapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:47:05 -0800","DDI-clinical-trial","evidence-challenges","Propranolol – The coadministration of nefazodone (200 mg BID) and propranolol (40 mg BID) for 5.5 days to healthy male volunteers (n = 18), including 3 poor and 15 extensive CYP2D6 metabolizers, resulted in 30% and 14% reductions in Cmax and AUC of propranolol, respectively, and a 14% reduction in Cmax for the metabolite, 4-hydroxypropranolol. The kinetics of nefazodone, hydroxynefazodone, and triazole-dione were not affected by coadministration of propranolol. However, Cmax, Cmin, and AUC of m-chlorophenylpiperazine were increased by 23%, 54%, and 28%, respectively. No change in initial dose of either drug is necessary and dose adjustments should be made on the basis of clinical response.","ncit:negative","ncit:quantitative",,"hydroxynefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","200","propranolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","BID","Oral","5.5","BID","Oral","5.5","18","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:21:50 -0700","drug-drug-interaction","evidence-supports","Results from drug interaction studies and population PK analyses from clinical studies indicate coadministration of XARELTO with a combined P-gp and strong CYP3A4 inducer (e.g., rifampicin, phenytoin) decreased rivaroxaban exposure by up to 50%.","ncit:positive","ncit:Qualitative","decreased rivaroxaban exposure by up to 50%.","rifampicin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"rivaroxaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 14:33:34 -0800","DDI-clinical-trial","evidence-supports"," When fluoxetine (20 mg QD) and nefazodone (200 mg BID) were administered at steady state there were no changes in the pharmacokinetic parameters for fluoxetine or its metabolite, norfluoxetine. Similarly, there were no changes in the pharmacokinetic parameters of nefazodone or HO-NEF; however, the mean AUC levels of the nefazodone metabolites mCPP and triazole-dione increased by 3 to 6 fold and 1.3 fold, respectively","ncit:positive","ncit:quantitative",,"mCPP","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","200","fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","BID","Oral","UNK","QD","Oral","UNK","UNK","3 to 6","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a971ea18-40cf-4a01-b696-180ccc3fddb5.html","2016-02-29 14:04:47 -0700","drug-drug-interaction","evidence-supports","Concomitant administration of propranolol with phenothiazines results in increased plasma levels of both drugs.","ncit:positive","ncit:Qualitative","results in increased plasma levels of both drugs","propranolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"phenothiazines","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-31 12:54:41 -0700","drug-drug-interaction","evidence-challenges","Data from drug-drug interactions studies involving coadministration of gemfibrozil, niacin, itraconazole, erythromycin, tolbutamide or clopidogrel indicate that the PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with any of these drugs.","ncit:negative","ncit:Qualitative","PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with gemfibrozil","gemfibrozil","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"fluvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 12:34:19 -0700","DDI-clinical-trial","evidence-supports","Fluvoxamine, a CYP1A2 inhibitor, decreases the clearance of olanzapine. This results in a mean increase in olanzapine Cmax following fluvoxamine of 54% in female nonsmokers and 77% in male smokers. The mean increase in olanzapine AUC is 52% and 108%, respectively.","ncit:positive","ncit:quantitative","range in AUC and Cmax changes for female nonsmokers and male smokers","fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","olanzapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","52-108","Percent","Increase","UNK","UNK","UNK","54 - 77\\\\n54-77","Percent","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:24:20 -0700","drug-drug-interaction","evidence-challenges","Similarly, chlorpromazine in combination with zolpidem produced no pharmacokinetic interaction, but there was an additive effect of decreased alertness and psychomotor performance [see Clinical Pharmacology (12.3)].","ncit:negative","ncit:Qualitative","produced no pharmacokinetic interaction,","zolpidem","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","chlorpromazine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4b0700c9-b417-4c3a-b36f-de461e125bd3.html","2015-11-29 13:36:22 -0700","DDI-clinical-trial","evidence-challenges","No clinically relevant effect was observed on steady state lithium exposure following coadministration with multiple daily doses of BRINTELLIX.","ncit:negative","ncit:quantitative",,"lithium","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","BRINTELLIX","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a971ea18-40cf-4a01-b696-180ccc3fddb5.html","2016-02-29 16:08:19 -0500","drug-drug-interaction","evidence-supports","Phenothiazines may lower the convulsive threshold; dosage adjustments of anticonvulsants may be necessary. Potentiation of anticonvulsant effects does not occur. However, it has been reported that phenothiazines may interfere with the metabolism of Dilantin®‡ (phenytoin) and thus precipitate Dilantin (phenytoin) toxicity.","ncit:positive","ncit:Qualitative","phenothiazines may precipitate Dilantin toxicity","Dilantin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Phenothiazines","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 11:01:28 -0700","drug-drug-interaction","evidence-challenges","In dedicated studies conducted in healthy subjects, famotidine, atenolol, prasugrel, and enoxaparin did not meaningfully alter the pharmacokinetics of apixaban.","ncit:negative","ncit:Qualitative","enoxaparin did not meaningfully alter the pharmacokinetics of apixaban","enoxaparin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"apixaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 16:11:19 -0700","drug-drug-interaction","evidence-supports","Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin. (See CONTRAINDICATIONS, WARNINGS, Myopathy/Rhabdomyolysis, and CLINICAL PHARMACOLOGY, Pharmacokinetics.)","ncit:positive","ncit:Qualitative","posaconazole is a strong inhibitor of CYP3A4 and reduces the elimination of lovastatin","lovastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","posaconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 19:19:02 -0400","drug-drug-interaction","evidence-supports","Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin. (See CONTRAINDICATIONS, WARNINGS, Myopathy/Rhabdomyolysis, and CLINICAL PHARMACOLOGY, Pharmacokinetics.)","ncit:positive","ncit:Qualitative","Cobicistat is a strong inhibitor of CYP3A4 and reduces the elimination of lovastatin","lovastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","cobicistat","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 12:06:08 -0800","DDI-clinical-trial","evidence-supports","HMG-CoA Reductase Inhibitors – When single 40 mg doses of simvastatin or atorvastatin, both substrates of CYP3A4, were given to healthy adult volunteers who had received nefazodone hydrochloride, 200 mg BID for 6 days, approximately 20 fold increases in plasma concentrations of simvastatin and simvastatin acid and 3 to 4 fold increases in plasma concentrations of atorvastatin and atorvastatin lactone were seen. These effects appear to be due to the inhibition of CYP3A4 by nefazodone because, in the same study, nefazodone had no significant effect on the plasma concentrations of pravastatin, which is not metabolized by CYP3A4 to a clinically significant extent","ncit:positive","ncit:quantitative","entered plasma concentration as AUC","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","atorvastatin lactone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","40","SD","Oral","1","BID","Oral","6","UNK","3 to 4","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 10:42:44 -0800","DDI-clinical-trial","evidence-challenges","There were also no changes in the pharmacokinetics of nefazodone or its triazole-dione metabolite, but the AUC and Cmax of mCPP increased by 44% and 48%, respectively, while the AUC of HO-NEF decreased by 19%. No changes in doses of either nefazodone or desipramine are necessary when the two drugs are given concomitantly. Subsequent dose adjustments should be made on the basis of clinical response.","ncit:negative","ncit:quantitative",,"nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","150","desipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","75","BID","Oral","UNK","QD","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4b0700c9-b417-4c3a-b36f-de461e125bd3.html","2015-11-29 13:44:17 -0700","DDI-clinical-trial","evidence-challenges","Coadministration of aspirin 150 mg/day with multiple daily doses of BRINTELLIX had no significant inhibitory effect on platelet aggregation or pharmacokinetics of aspirin and salicylic acid [see Drug Interactions (7.4)].","ncit:negative","ncit:quantitative",,"BRINTELLIX","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","aspirin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","150","Daily","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5429f134-839f-4ffc-9944-55f51238def8.html","2015-12-18 15:57:58 -0500","DDI-clinical-trial","evidence-supports","Coadministration of paroxetine with SAPHRIS caused a two-fold increase in the maximum plasma concentrations and systemic exposure of paroxetine. Asenapine enhances the inhibitory effects of paroxetine on its own metabolism by CYP2D6.","ncit:positive","ncit:quantitative",,"paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","SAPHRIS","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","2","Fold","Increase","UNK","UNK","UNK","2","Fold","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 10:44:04 -0800","DDI-clinical-trial","evidence-challenges","There were also no changes in the pharmacokinetics of nefazodone or its triazole-dione metabolite, but the AUC and Cmax of mCPP increased by 44% and 48%, respectively, while the AUC of HO-NEF decreased by 19%. No changes in doses of either nefazodone or desipramine are necessary when the two drugs are given concomitantly. Subsequent dose adjustments should be made on the basis of clinical response.","ncit:negative","ncit:quantitative",,"desipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","75","triazole-dione","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","150","BID","Oral","UNK","QD","Oral","UNK","UNK","UNK","UNK","UNK","UNKUNUNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 15:35:32 -0700","DDI-clinical-trial","evidence-supports","Quinidine: Quinidine was given as a 200 mg dose every 2 hours up to a total dose of 1000 mg. Dabigatran etexilate was given over 3 consecutive days, the last evening dose on Day 3 with or without quinidine pre-dosing. Concomitant quinidine administration increased dabigatran’s AUC and Cmax by 53% and 56%, respectively.","ncit:positive","ncit:quantitative","Note: quinidine regimen marked as unknown since Q2H up to 1000mg","quinidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","up to 1000","dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","3","UNK","Oral","UNK","UNK","53","Percent","Increase","UNKUNUNK","UNK","UNK","56","Percent","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2015-11-29 14:46:00 -0700","DDI-clinical-trial","evidence-supports","Fluoxetine: Co-administration of fluoxetine (20 mg twice daily for 21 days), a potent inhibitor of CYP2D6, with a single 3 mg dose of iloperidone to 23 healthy volunteers, ages 29 to 44 years, who were classified as CYP2D6 extensive metabolizers, increased the AUC of iloperidone and its metabolite P88, by about 2- to 3-fold, and decreased the AUC of its metabolite P95 by one-half. Iloperidone doses should be reduced by one-half when administered with fluoxetine. ","ncit:positive","ncit:quantitative",,"P88","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","3","fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","SD","Oral","1","BID","Oral","21","23","2 to 3","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:43:01 -0700","drug-drug-interaction","evidence-supports","Concomitant treatment with CLOZARIL and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology (12.3)]. Use caution and monitor patients closely when using such inhibitors. Consider reducing the CLOZARIL dose [see Dosage and Administration (2.6)]","ncit:positive","ncit:Qualitative","Terbinafine can increase clozapine levels","clozapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","terbinafine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 16:08:43 -0700","drug-drug-interaction","evidence-challenges","In clinical studies exploring CYP3A4, CYP2C9, P-gp and other pathways, dabigatran did not meaningfully alter the pharmacokinetics of amiodarone, atorvastatin, clarithromycin, diclofenac, clopidogrel, digoxin, pantoprazole, or ranitidine.","ncit:negative","ncit:Qualitative","dabigatran did not meaningfully alter the pharmacokinetics of ranitidine","ranitidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 18:07:55 -0700","DDI-clinical-trial","evidence-challenges"," There is no pharmacokinetic interaction between zaleplon and diphenhydramine following the administration of a single dose (10 mg and 50 mg, respectively) of each drug. However, because both of these compounds have CNS effects, an additive pharmacodynamic effect is possible.","ncit:negative","ncit:quantitative","no pharmacokinetic interaction between zaleplon and diphenhydramine","diphenhydramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","50","zaleplon","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","10","SD","Oral","1","SD","Oral","1","UNK","UNK","UNK","UNK","UNKUNUNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-30 15:07:23 -0700","drug-drug-interaction","evidence-supports","Administration of fluvastatin 40 mg single dose to healthy volunteers pre-treated with fluconazole for 4 days results in an increase of fluvastatin exposure. Therefore, in patients taking fluconazole, therapy should be limited to fluvastatin 20 mg twice daily [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative","Concomitant fluconazole increases fluvastatin exposure. Details in Section 12 Table 3","fluconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"fluvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:27:07 -0700","drug-drug-interaction","evidence-supports","In drug interaction studies evaluating the concomitant use with drugs that are combined P-gp and CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin, erythromycin and fluconazole), increases in rivaroxaban exposure and pharmacodynamic effects (i.e., factor Xa inhibition and PT prolongation) were observed. The increases in exposure ranged from 30% to 160%. Significant increases in rivaroxaban exposure may increase bleeding risk [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative","increases in rivaroxaban exposure","fluconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"rivaroxaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d78e9639-6fab-4a78-8b29-6991a18ae6c6.html","2016-02-19 17:46:51 -0500","drug-drug-interaction","evidence-supports","In one study of 45 elderly patients suffering from dementia treated with perphenazine, the 5 patients who were prospectively identified as poor P450 2D6 metabolizers had reported significantly greater side effects during the first 10 days of treatment than the 40 extensive metabolizers, following which the groups tended to converge. Prospective phenotyping of elderly patients prior to antipsychotic treatment may identify those at risk for adverse events. The concomitant administration of other drugs that inhibit the activity of P450 2D6 may acutely increase plasma concentrations of antipsychotics. Among these are tricyclic antidepressants and selective serotonin reuptake inhibitors, e.g., fluoxetine, sertraline and paroxetine. When prescribing these drugs to patients already receiving antipsychotic therapy, close monitoring is essential and dose reduction may become necessary to avoid toxicity. Lower doses than usually prescribed for either the antipsychotic or the other drug may be required.","ncit:positive","ncit:Qualitative","may acutely increase plasma concentrations of antipsychotics.","sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"perphenazine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-30 15:11:14 -0700","drug-drug-interaction","evidence-supports","Bleeding and/or increased prothrombin times have been reported in patients taking coumarin anticoagulants concomitantly with other HMG-CoA reductase inhibitors. Therefore, patients receiving warfarin-type anticoagulants should have their prothrombin times closely monitored when fluvastatin sodium is initiated or the dosage of fluvastatin sodium is changed.","ncit:positive","ncit:Qualitative","Concomitant fluvastatin and warfarin have been reported to increase prothrombin time","warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/fdbfe194-b845-42c5-bb87-a48118bc72e7.html","2016-03-31 12:38:39 -0700","drug-drug-interaction","evidence-supports","Elevated plasma levels of HMG-CoA reductase inhibitory activity increases the risk of myopathy and rhabdomyolysis, particularly with higher doses of simvastatin. [See Warnings and Precautions (5.1) and Clinical Pharmacology (12.3).] Concomitant use of drugs labeled as having a strong inhibitory effect on CYP3A4 is contraindicated [see Contraindications (4)]. If treatment with itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with simvastatin must be suspended during the course of treatment.","ncit:positive","ncit:Qualitative","strong inhibitor of CYP3A4 may elevate simvastatin plasma level","simvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","clarithromycin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/49c4105b-e518-481c-a248-6684135f5bc1.html","2015-11-29 16:36:20 -0700","DDI-clinical-trial","evidence-challenges","Repeated oral doses of risperidone (4 mg once daily) did not affect the pre-dose or average plasma concentrations and exposure (AUC) of valproate (1000 mg/day in three divided doses) compared to placebo (n=21). However, there was a 20% increase in valproate peak plasma concentration (Cmax) after concomitant administration of risperidone. Dose adjustment for valproate is not recommended.","ncit:negative","ncit:quantitative",,"valproate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","1000","risperidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","4","Daily","Oral","UNK","QD","Oral","UNK","21","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1fd0ba23-962e-427f-8b9d-2cf8f64d0f95.html","2016-03-31 11:20:38 -0700","drug-drug-interaction","evidence-supports","CRESTOR significantly increased INR in patients receiving coumarin anticoagulants. Therefore, caution should be exercised when coumarin anticoagulants are given in conjunction with CRESTOR. In patients taking coumarin anticoagulants and CRESTOR concomitantly, INR should be determined before starting CRESTOR and frequently enough during early therapy to ensure that no significant alteration of INR occurs [seeWarnings and Precautions (5.3) and Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative","CRESTOR significantly increased INR in patients receiving coumarin anticoagulants. Study details in Section 12 Table 5","CRESTOR","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"coumarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 15:29:51 -0700","DDI-clinical-trial","evidence-supports","Amiodarone: When dabigatran etexilate was coadministered with a single 600 mg oral dose of amiodarone, the dabigatran AUC and Cmax increased by 58% and 50%, respectively. The increase in exposure was mitigated by a 65% increase in the renal clearance of dabigatran in the presence of amiodarone. The increase in renal clearance may persist after amiodarone is discontinued because of amiodarone’s long half-life. In the population pharmacokinetics study from RE-LY, no important changes in dabigatran trough levels were observed in patients who received amiodarone.","ncit:positive","ncit:quantitative",,"dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","amiodarone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","UNK","Oral","UNK","SD","Oral","1","UNK","58","Percent","Increase","65","Percent","Increase","50","Percent","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 11:01:28 -0700","drug-drug-interaction","evidence-challenges","In dedicated studies conducted in healthy subjects, famotidine, atenolol, prasugrel, and enoxaparin did not meaningfully alter the pharmacokinetics of apixaban.","ncit:negative","ncit:Qualitative","famotidine did not meaningfully alter the pharmacokinetics of apixaban","apixaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","famotidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 16:06:42 -0700","drug-drug-interaction","evidence-supports","Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin. (See CONTRAINDICATIONS, WARNINGS, Myopathy/Rhabdomyolysis, and CLINICAL PHARMACOLOGY, Pharmacokinetics.)","ncit:positive","ncit:Qualitative","itraconazole is a strong inhibitor of cyP3A4 and reduces elimination of lovastatin","itraconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"lovastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a0da0dba-a56d-486b-a45b-e8a7cdfbeac6.html","2016-05-10 10:32:01 -0700","DDI-clinical-trial","evidence-supports","Coadministration of cimetidine increased the maximum plasma concentration of triazolam by 51%, decreased clearance by 55%, and increased half-life by 68%; caution and consideration of appropriate triazolam dose reduction are recommended.","ncit:positive","ncit:quantitative",,"cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","triazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","55","Percent","Decrease","51","Percent","Increase","68","Percent","Increase" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:54:42 -0700","drug-drug-interaction","evidence-challenges","Zolpidem tartrate had no effect on digoxin pharmacokinetics","ncit:negative","ncit:Qualitative","had no effect on digoxin pharmacokinetics","digoxin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Zolpidem","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 16:00:33 -0700","drug-drug-interaction","evidence-challenges","Diclofenac, Ranitidine, and Digoxin: None of these drugs alters exposure to dabigatran.","ncit:negative","ncit:Qualitative","digoxin does not alter exposure to dabigatran.","Digoxin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:44:42 -0700","DDI-clinical-trial","evidence-supports","Erythromycin (combined P-gp and moderate CYP3A4 inhibitor): Both the single-dose rivaroxaban AUC and Cmax increased by 30%","ncit:positive","ncit:quantitative",,"Erythromycin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","rivaroxaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","30","Percent","Increase","UNK","UNK","UNK","30","Percent","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 13:51:32 -0800","DDI-clinical-trial","evidence-supports","Buspirone – In a study of steady-state pharmacokinetics in healthy volunteers, coadministration of buspirone (2.5 or 5 mg BID) with nefazodone (250 mg BID) resulted in marked increases in plasma buspirone concentrations (increases up to 20 fold in Cmax and up to 50 fold in AUC) and statistically significant decreases (about 50%) in plasma concentrations of the buspirone metabolite 1-pyrimidinylpiperazine. ","ncit:positive","ncit:quantitative",,"buspirone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","2.5 or 5","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","250","BID","Oral","UNK","BID","Oral","UNK","UNK","up to 50","Fold","Increase","UNK","UNK","UNK","up to 20","Fold","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 12:56:43 -0800","DDI-clinical-trial","evidence-supports","Interaction studies of nefazodone with two triazolobenzodiazepines, i.e., triazolam and alprazolam, metabolized by cytochrome P450 3A4, have revealed substantial and clinically important increases in plasma concentrations of these compounds when administered concomitantly with nefazodone.","ncit:positive","ncit:quantitative","increases in plasma concentrations","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","triazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 12:05:05 -0800","drug-drug-interaction","evidence-supports","The coadministration of triazolam and nefazodone causes a significant increase in the plasma level of triazolam (see WARNINGS and PRECAUTIONS), and a 75% reduction in the initial triazolam dosage is recommended if the two drugs are to be given together. ","ncit:positive","ncit:Qualitative","increase in the plasma level of triazolam","triazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2016-02-18 18:45:32 -0500","DDI-clinical-trial","evidence-supports","Paroxetine: Co-administration of paroxetine (20 mg/day for 5 to 8 days), a potent inhibitor of CYP2D6, with multiple doses of iloperidone (8 or 12 mg twice daily) to patients with schizophrenia ages 18 to 65 years resulted in increased mean steady-state peak concentrations of iloperidone and its metabolite P88, by about 1.6-fold, and decreased mean steady-state peak concentrations of its metabolite P95 by one-half. Iloperidone doses should be reduced by one-half when administered with paroxetine. ","ncit:positive","ncit:quantitative",,"P88","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","8 or 12","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","BID","Oral","UNK","Daily","Oral","5 to 8","UNK","UNK","UNK","UNK","UNK","UNK","UNK","1.6","Fold","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:28:00 -0700","DDI-clinical-trial","evidence-challenges","A study involving haloperidol and zolpidem revealed no effect of haloperidol on the pharmacokinetics or pharmacodynamics of zolpidem. The lack of a drug interaction following single-dose administration does not predict the absence of an effect following chronic administration [see Clinical Pharmacology (12.3)].","ncit:negative","ncit:quantitative","no effect of haloperidol on the pharmacokinetics or pharmacodynamics of zolpidem.","haloperidol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","zolpidem","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","SD","Oral","1","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:37:21 -0700","DDI-clinical-trial","evidence-supports","Following five consecutive nightly doses at bedtime of oral zolpidem tartrate 10 mg in the presence of sertraline 50 mg (17 consecutive daily doses, at 7:00 am, in healthy female volunteers), zolpidem Cmax was significantly higher (43%) and Tmax was significantly decreased (-53%). Pharmacokinetics of sertraline and N-desmethylsertraline were unaffected by zolpidem.","ncit:positive","ncit:quantitative","max was significantly decreased (-53%).","zolpidem","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","10","sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","50","QD","Oral","5","QD","Oral","17","UNK","UNK","UNK","UNK","UNK","UNK","UNK","43","Percent","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 16:22:18 -0700","DDI-clinical-trial","evidence-challenges"," Olanzapine did not influence the pharmacokinetics of diazepam or its active metabolite N-desmethyldiazepam.","ncit:negative","ncit:quantitative",,"Olanzapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","diazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 10:51:40 -0800","DDI-clinical-trial","evidence-challenges","Lithium – In 13 healthy subjects the coadministration of nefazodone (200 mg BID) with lithium (500 mg BID) for 5 days (steady-state conditions) was found to be well tolerated. When the two drugs were coadministered, there were no changes in the steady-state pharmacokinetics of either lithium, nefazodone, or its metabolite HO-NEF; however, there were small decreases in the steady-state plasma concentrations of two nefazodone metabolites, mCPP and triazole-dione, which are considered not to be of clinical significance. Therefore, no dosage adjustment of either lithium or nefazodone is required when they are coadministered.","ncit:negative","ncit:quantitative",,"Lithium","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","500","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","200","BID","Oral","5","BID","Oral","5","13","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:51:10 -0800","DDI-clinical-trial","evidence-supports","Propranolol – The coadministration of nefazodone (200 mg BID) and propranolol (40 mg BID) for 5.5 days to healthy male volunteers (n = 18), including 3 poor and 15 extensive CYP2D6 metabolizers, resulted in 30% and 14% reductions in Cmax and AUC of propranolol, respectively, and a 14% reduction in Cmax for the metabolite, 4-hydroxypropranolol. The kinetics of nefazodone, hydroxynefazodone, and triazole-dione were not affected by coadministration of propranolol. However, Cmax, Cmin, and AUC of m-chlorophenylpiperazine were increased by 23%, 54%, and 28%, respectively. No change in initial dose of either drug is necessary and dose adjustments should be made on the basis of clinical response.","ncit:positive","ncit:quantitative",,"m-chlorophenylpiperazine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","200","propranolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","BID","Oral","5.5","BID","Oral","5.5","18","28","Percent","Increase","UNK","UNK","UNK","23","Percent","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/036db1f2-52b3-42a0-acf9-817b7ba8c724.html","2015-12-08 18:59:13 -0700","DDI-clinical-trial","evidence-challenges","Consistent with in vitro results, a study in normal healthy volunteers showed that ziprasidone did not alter the metabolism of dextromethorphan, a CYP2D6 model substrate, to its major metabolite, dextrorphan. There was no statistically significant change in the urinary dextromethorphan/dextrorphan ratio.","ncit:negative","ncit:quantitative",,"dextrorphan","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","ziprasidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4b0700c9-b417-4c3a-b36f-de461e125bd3.html","2015-11-29 15:59:31 -0500","DDI-clinical-trial","evidence-challenges","Because vortioxetine is highly bound to plasma protein, coadministration of BRINTELLIX with another drug that is highly protein bound may increase free concentrations of the other drug. However, in a clinical study with coadministration of BRINTELLIX (10 mg/day) and warfarin (1 mg/day to 10 mg/day), a highly protein-bound drug, no significant change in INR was observed [see Drug Interactions (7.2)].","ncit:negative","ncit:quantitative",,"warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","1 to 10","BRINTELLIX","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","Daily","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 15:55:48 -0700","DDI-clinical-trial","evidence-supports","Clopidogrel: When dabigatran etexilate was given concomitantly with a loading dose of 300 mg or 600 mg clopidogrel, the dabigatran AUC and Cmax increased by approximately 30% and 40%, respectively. The concomitant administration of dabigatran etexilate and clopidogrel resulted in no further prolongation of capillary bleeding times compared to clopidogrel monotherapy. When comparing combined treatment and the respective mono-treatments, the coagulation measures for dabigatran’s effect (aPTT, ECT, and TT) remained unchanged, and inhibition of platelet aggregation (IPA), a measurement of clopidogrel’s effect, remained unchanged.","ncit:positive","ncit:quantitative",,"clopidogrel","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","300 or 600","dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","SD","Oral","1","UNK","30","Percent","Increase","UNK","UNK","UNK","40","Percent","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-02-18 18:51:21 -0500","DDI-clinical-trial","evidence-supports","A pharmacokinetic study was conducted in 16 schizophrenic patients who received clozapine under steady-state conditions. After coadministration of fluvoxamine for 14 days, mean trough concentrations of clozapine and its metabolites, N-desmethylclozapine and clozapine N-oxide, were elevated about 3-fold compared to baseline steady-state concentrations","ncit:positive","ncit:quantitative",,"clozapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","14","16","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/7b8e5b26-b9e4-4704-921b-3c3c0d159916.html","2015-11-29 16:18:02 -0700","DDI-clinical-trial","evidence-supports","Co-administration of INVEGA® 6 mg once daily with carbamazepine, a strong inducer of both CYP3A4 and P-glycoprotein (P-gp), at 200 mg twice daily caused a decrease of approximately 37% in the mean steady-state Cmax and AUC of paliperidone. This decrease is caused, to a substantial degree, by a 35% increase in renal clearance of paliperidone. A minor decrease in the amount of drug excreted unchanged in the urine suggests that there was little effect on the CYP metabolism or bioavailability of paliperidone during carbamazepine co-administration.","ncit:positive","ncit:quantitative",,"carbamazepine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","INVEGA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","6","QD","Oral","UNK","BID","Oral","UNK","UNK","37","Percent","Decrease","35","Percent","Increase","37","Percent","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/44dcbf97-99ec-427c-ba50-207e0069d6d2.html","2016-03-31 10:14:00 -0700","drug-drug-interaction","evidence-supports","Cyclosporine significantly increased pitavastatin exposure. Co-administration of cyclosporine with LIVALO is contraindicated [see Contraindications (4) and Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative","Cyclosporine significantly increased pitavastatin exposure. Study details in Section 12 Table 3","Cyclosporine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"pitavastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 10:40:46 -0800","DDI-clinical-trial","evidence-challenges","Desipramine – When nefazodone (150 mg BID) and desipramine (75 mg QD) were administered together there were no changes in the pharmacokinetics of desipramine or its metabolite, 2-hydroxy desipramine. ","ncit:negative","ncit:quantitative",,"nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","150","Desipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","75","QD","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 17:32:41 -0700","DDI-clinical-trial","evidence-challenges"," In another study, single doses of warfarin (15 mg) and XARELTO (5 mg) resulted in an additive effect on factor Xa inhibition and PT. Warfarin did not affect the pharmacokinetics of rivaroxaban.","ncit:negative","ncit:quantitative","Warfarin did not affect the pharmacokinetics of rivaroxaban","rivaroxaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","5","warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","15","SD","Oral","1","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a0da0dba-a56d-486b-a45b-e8a7cdfbeac6.html","2016-05-10 10:37:18 -0700","DDI-clinical-trial","evidence-supports","Coadministration of isoniazid increased the maximum plasma concentration of triazolam by 20%, decreased clearance by 42%, and increased half-life by 31%.","ncit:positive","ncit:quantitative",,"isoniazid","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","triazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","42","Percent","Decrease","20","Percent","Increase","31","Percent","Increase" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 17:39:20 -0700","DDI-clinical-trial","evidence-challenges","Imipramine: Coadministration of single doses of Zaleplon 20 mg and imipramine 75 mg produced additive effects on decreased alertness and impaired psychomotor performance for 2 to 4 hours after administration. The interaction was pharmacodynamic with no alteration of the pharmacokinetics of either drug","ncit:negative","ncit:quantitative","no alteration of the pharmacokinetics of either drug","Zaleplon","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","imipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","75","SD","Oral","1","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4b0700c9-b417-4c3a-b36f-de461e125bd3.html","2015-11-29 13:38:00 -0700","DDI-clinical-trial","evidence-challenges","Multiple doses of BRINTELLIX did not affect the pharmacokinetics or pharmacodynamics (composite cognitive score) of diazepam.","ncit:negative","ncit:quantitative",,"diazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","BRINTELLIX","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/fdbfe194-b845-42c5-bb87-a48118bc72e7.html","2016-03-31 12:22:33 -0700","drug-drug-interaction","evidence-supports","Elevated plasma levels of HMG-CoA reductase inhibitory activity increases the risk of myopathy and rhabdomyolysis, particularly with higher doses of simvastatin. [See Warnings and Precautions (5.1) and Clinical Pharmacology (12.3).] Concomitant use of drugs labeled as having a strong inhibitory effect on CYP3A4 is contraindicated [see Contraindications (4)]. If treatment with itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with simvastatin must be suspended during the course of treatment.","ncit:positive","ncit:Qualitative","strong inhibitor of CYP3A4 may elevate simvastatin plasma level","posaconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"simvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 20:54:45 -0400","DDI-clinical-trial","evidence-challenges","In addition, there were no significant pharmacokinetic interactions observed in studies comparing concomitant rivaroxaban 20 mg and 7.5 mg single dose of midazolam (substrate of CYP3A4), 0.375 mg once-daily dose of digoxin (substrate of P-gp), or 20 mg once daily dose of atorvastatin (substrate of CYP3A4 and P-gp) in healthy volunteers.","ncit:negative","ncit:quantitative","no significant pharmacokinetic interactions observed","atorvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","rivaroxaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","20","UNK","Oral","UNK","QD","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 13:03:19 -0800","DDI-clinical-trial","evidence-challenges","Nefazodone plasma concentrations were unaffected by triazolam.","ncit:negative","ncit:quantitative",,"Nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","200","triazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",".25","BID","Oral","UNK","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 17:41:00 -0700","DDI-clinical-trial","evidence-challenges","In two drug interaction studies where clopidogrel (300 mg loading dose followed by 75 mg daily maintenance dose) and XARELTO (15 mg single dose) were coadministered in healthy subjects, an increase in bleeding time to 45 minutes was observed in approximately 45% and 30% of subjects in these studies, respectively. The change in bleeding time was approximately twice the maximum increase seen with either drug alone. There was no change in the pharmacokinetics of either drug.","ncit:negative","ncit:quantitative","There was no change in the pharmacokinetics of either drug.","XARELTO","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","15","clopidogrel","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","75","SD","Oral","1","QD","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/036db1f2-52b3-42a0-acf9-817b7ba8c724.html","2015-12-08 19:04:34 -0700","DDI-clinical-trial","evidence-challenges","Population pharmacokinetic analysis of schizophrenic patients enrolled in controlled clinical trials has not revealed evidence of any clinically significant pharmacokinetic interactions with benztropine, propranolol, or lorazepam. The absolute bioavailability of a 20 mg dose under fed conditions is approximately 60%. The absorption of ziprasidone is increased up to two-fold in the presence of food","ncit:negative","ncit:quantitative",,"benztropine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","ziprasidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:05:41 -0800","DDI-clinical-trial","evidence-challenges","When nefazodone (200 mg BID) and cimetidine (300 mg QID) were coadministered for one week, no change in the steady-state pharmacokinetics of either nefazodone or cimetidine was observed compared to each dosed alone. Therefore, dosage adjustment is not necessary for either drug when coadministered.","ncit:negative","ncit:quantitative",,"cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","300","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","QID","Oral","7","BID","Oral","7","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/49c4105b-e518-481c-a248-6684135f5bc1.html","2015-11-29 16:36:20 -0700","DDI-clinical-trial","evidence-challenges","Repeated oral doses of risperidone (3 mg twice daily) did not affect the exposure (AUC) or peak plasma concentrations (Cmax) of lithium (n=13). Dose adjustment for lithium is not recommended.","ncit:negative","ncit:quantitative",,"lithium","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","risperidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","3","UNK","Oral","UNK","BID","Oral","UNK","13","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/44dcbf97-99ec-427c-ba50-207e0069d6d2.html","2016-03-31 10:15:25 -0700","drug-drug-interaction","evidence-supports","Erythromycin significantly increased pitavastatin exposure. In patients taking erythromycin, a dose of LIVALO 1 mg once daily should not be exceeded [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)]. ","ncit:positive","ncit:Qualitative","rythromycin significantly increased pitavastatin exposure. Study details in Section 12 Table 3","pitavastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","erythromycin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 12:37:44 -0700","DDI-clinical-trial","evidence-supports","Fluoxetine (60 mg single dose or 60 mg daily dose for 8 days) causes a small (mean 16%) increase in the maximum concentration of olanzapine and a small (mean 16%) decrease in olanzapine clearance","ncit:positive","ncit:quantitative",,"Fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","60","olanzapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","QD","Oral","8","UNK","UNKUNK","UNK","UNK","16","Percent","Decrease","16","Percent","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 10:49:34 -0700","drug-drug-interaction","evidence-supports","Avoid concomitant use of ELIQUIS with strong dual inducers of CYP3A4 and P-gp (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort) because such drugs will decrease exposure to apixaban [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative","carbamezepine will decrease exposure to apixaban","carbamazepine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"apixaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 17:43:16 -0700","DDI-clinical-trial","evidence-challenges","In two drug interaction studies where clopidogrel (300 mg loading dose followed by 75 mg daily maintenance dose) and XARELTO (15 mg single dose) were coadministered in healthy subjects, an increase in bleeding time to 45 minutes was observed in approximately 45% and 30% of subjects in these studies, respectively. The change in bleeding time was approximately twice the maximum increase seen with either drug alone. There was no change in the pharmacokinetics of either drug.","ncit:negative","ncit:quantitative","There was no change in the pharmacokinetics of either drug.","clopidogrel","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","15","XARELTO","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","75","SD","UNK","1","QD","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 13:57:09 -0800","DDI-clinical-trial","evidence-supports","Buspirone – In a study of steady-state pharmacokinetics in healthy volunteers, coadministration of buspirone (2.5 or 5 mg BID) with nefazodone (250 mg BID) resulted in marked increases in plasma buspirone concentrations (increases up to 20 fold in Cmax and up to 50 fold in AUC) and statistically significant decreases (about 50%) in plasma concentrations of the buspirone metabolite 1-pyrimidinylpiperazine.","ncit:positive","ncit:quantitative",,"nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","250","1-pyrimidinylpiperazine.","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","2.5 or 5","BID","Oral","UNK","BID","Oral","UNK","UNK","about 50","Percent","Decrease","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/39a5dae2-49f7-4662-9eac-aa7b4c7807a4.html","2016-05-09 16:28:30 -0700","DDI-clinical-trial","evidence-supports","Eszopiclone and lorazepam decreased each other's Cmax by 22%. ","ncit:positive","ncit:quantitative",,"Eszopiclone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","lorazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","22","Percent","Decrease","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1fd0ba23-962e-427f-8b9d-2cf8f64d0f95.html","2016-03-31 11:07:53 -0700","DDI-clinical-trial","evidence-supports","Cyclosporine increased rosuvastatin exposure (AUC) 7‑fold. Therefore, in patients taking cyclosporine, the dose of CRESTOR should not exceed 5 mg once daily [seeDosage and Administration (2.5), Warnings and Precautions (5.1), and Clinical Pharmacology (12.3)].","ncit:positive","ncit:quantitative","Study details in section 12 Table 4","cyclosporine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","rosuvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","7","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-12 13:35:35 -0400","drug-drug-interaction","evidence-challenges"," Diclofenac, Ranitidine, and Digoxin: None of these drugs alters exposure to dabigatran.","ncit:negative","ncit:Qualitative","diclofenac does not alter exposure to dabigatran","dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Diclofenac","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 14:24:30 -0800","DDI-clinical-trial","evidence-challenges"," When fluoxetine (20 mg QD) and nefazodone (200 mg BID) were administered at steady state there were no changes in the pharmacokinetic parameters for fluoxetine or its metabolite, norfluoxetine.","ncit:negative","ncit:quantitative",,"fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","20","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","QD","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:26:31 -0700","drug-drug-interaction","evidence-supports","In drug interaction studies evaluating the concomitant use with drugs that are combined P-gp and CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin, erythromycin and fluconazole), increases in rivaroxaban exposure and pharmacodynamic effects (i.e., factor Xa inhibition and PT prolongation) were observed. The increases in exposure ranged from 30% to 160%. Significant increases in rivaroxaban exposure may increase bleeding risk [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative","increases in rivaroxaban exposure","ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"rivaroxaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 16:22:18 -0700","DDI-clinical-trial","evidence-challenges","Single doses of olanzapine did not affect the pharmacokinetics of warfarin ","ncit:negative","ncit:quantitative",,"warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","olanzapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/9c4bedb4-2d59-4fcd-aad7-fce988cd96d8.html","2016-02-29 14:20:40 -0700","drug-drug-interaction","evidence-supports","Reduced cytochrome P450 2D6 isozyme activity drugs that inhibit this isozyme (e.g., fluoxetine and paroxetine) and certain other drugs (e.g., fluvoxamine, propranolol, and pindolol) appear to appreciably inhibit the metabolism of thioridazine. The resulting elevated levels of thioridazine would be expected to augment the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as Torsades de pointes type arrhythmias.","ncit:positive","ncit:Qualitative","appear to appreciably inhibit the metabolism of thioridazine and result in elevated levels of thioridazine","thioridazine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:38:01 -0700","drug-drug-interaction","evidence-supports","Concomitant use of CLOZARIL and CYP1A2 inhibitors can increase plasma levels of clozapine, potentially resulting in adverse reactions. Reduce the CLOZARIL dose to one-third of the original dose when CLOZARIL is coadministered with strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin, or enoxacin). The CLOZARIL dose should be increased to the original dose when coadministration of strong CYP1A2 inhibitors is discontinued [see Dosage and Administration (2.6), Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative","enoxacin can increase clozapine levels","enoxacin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"clozapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4b0700c9-b417-4c3a-b36f-de461e125bd3.html","2015-11-29 13:52:49 -0700","DDI-clinical-trial","evidence-challenges","Furthermore, in a series of clinical drug interaction studies, coadministration of BRINTELLIX with substrates for CYP2B6 (e.g., bupropion), CYP2C9 (e.g., warfarin), and CYP2C19 (e.g., diazepam), had no clinical meaningful effect on the pharmacokinetics of these substrates (Figure 2).","ncit:negative","ncit:quantitative",,"bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","BRINTELLIX","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:36:49 -0700","drug-drug-interaction","evidence-supports","oncomitant use of CLOZARIL and CYP1A2 inhibitors can increase plasma levels of clozapine, potentially resulting in adverse reactions. Reduce the CLOZARIL dose to one-third of the original dose when CLOZARIL is coadministered with strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin, or enoxacin). The CLOZARIL dose should be increased to the original dose when coadministration of strong CYP1A2 inhibitors is discontinued [see Dosage and Administration (2.6), Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative","Fluvoxamine can increase clozapine levels","clozapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 17:35:47 -0700","DDI-clinical-trial","evidence-challenges","Thioridazine: Coadministration of single doses of Zaleplon 20 mg and thioridazine 50 mg produced additive effects on decreased alertness and impaired psychomotor performance for 2 to 4 hours after administration. The interaction was pharmacodynamic with no alteration of the pharmacokinetics of either drug.","ncit:negative","ncit:quantitative","no alteration of the pharmacokinetics of either drug.","thioridazine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","50","Zaleplon","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","20","SD","Oral","1","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 15:21:53 -0700","DDI-clinical-trial","evidence-supports","Ketoconazole: Systemic ketoconazole increased dabigatran AUC and Cmax values by 138% and 135%, respectively, after a single dose of 400 mg, and 153%, and 149%, respectively, after multiple daily doses of 400 mg.","ncit:positive","ncit:quantitative","This is multiple ketoconazole doses","ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","400","dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","QD","Oral","UNK","UNK","153","Percent","Increase","UNK","UNK","UNK","149","Percent","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 13:33:28 -0800","DDI-clinical-trial","evidence-challenges","Lorazepam – When lorazepam (2 mg BID) and nefazodone (200 mg BID) were coadministered to steady state, there was no change in any pharmacokinetic parameter for either drug compared to each drug administered alone. Therefore, dosage adjustment is not necessary for either drug when coadministered.","ncit:negative","ncit:quantitative",,"nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","200","Lorazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","2","BID","Oral","UNK","BID","Oral","UNK","UNK","UNKUNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 15:57:08 -0700","drug-drug-interaction","evidence-challenges","Digoxin: In patients with hypercholesterolemia, concomitant administration of lovastatin and digoxin resulted in no effect on digoxin plasma concentrations","ncit:negative","ncit:Qualitative","concomitant administration of lovastatin and digoxin resulted in no effect on digoxin plasma concentrations","lovastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"digoxin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/036db1f2-52b3-42a0-acf9-817b7ba8c724.html","2015-12-08 19:05:25 -0700","DDI-clinical-trial","evidence-challenges","Population pharmacokinetic analysis of schizophrenic patients enrolled in controlled clinical trials has not revealed evidence of any clinically significant pharmacokinetic interactions with benztropine, propranolol, or lorazepam. The absolute bioavailability of a 20 mg dose under fed conditions is approximately 60%. The absorption of ziprasidone is increased up to two-fold in the presence of food","ncit:negative","ncit:quantitative",,"ziprasidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","lorazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2015-11-29 14:55:02 -0700","DDI-clinical-trial","evidence-supports","Paroxetine: Co-administration of paroxetine (20 mg/day for 5 to 8 days), a potent inhibitor of CYP2D6, with multiple doses of iloperidone (8 or 12 mg twice daily) to patients with schizophrenia ages 18 to 65 years resulted in increased mean steady-state peak concentrations of iloperidone and its metabolite P88, by about 1.6-fold, and decreased mean steady-state peak concentrations of its metabolite P95 by one-half. Iloperidone doses should be reduced by one-half when administered with paroxetine. ","ncit:positive","ncit:quantitative",,"P95","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","8 or 12","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","BID","Oral","UNK","Daily","Oral","5 to 8","UNK","UNK","UNK","UNK","UNK","UNK","UNK","50","Percent","Decrease","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 14:01:56 -0800","DDI-clinical-trial","evidence-supports","With 5 mg BID doses of buspirone, slight increases in AUC were observed for nefazodone (23%) and its metabolites hydroxynefazodone (17%) and mCPP (9%).","ncit:positive","ncit:quantitative",,"buspirone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","5","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","250","BID","Oral","UNK","BID","Oral","UNK","UNK","23","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2015-11-29 14:46:00 -0700","DDI-clinical-trial","evidence-supports","Fluoxetine: Co-administration of fluoxetine (20 mg twice daily for 21 days), a potent inhibitor of CYP2D6, with a single 3 mg dose of iloperidone to 23 healthy volunteers, ages 29 to 44 years, who were classified as CYP2D6 extensive metabolizers, increased the AUC of iloperidone and its metabolite P88, by about 2- to 3-fold, and decreased the AUC of its metabolite P95 by one-half. Iloperidone doses should be reduced by one-half when administered with fluoxetine. ","ncit:positive","ncit:quantitative",,"fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","iloperidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","3","SD","Oral","1","BID","Oral","21","23","2 to 3","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1fd0ba23-962e-427f-8b9d-2cf8f64d0f95.html","2016-03-31 14:25:54 -0400","drug-drug-interaction","evidence-challenges","When CRESTOR was coadministered with fenofibrate, no clinically significant increase in the AUC of rosuvastatin or fenofibrate was observed. Because it is known that the risk of myopathy during treatment with HMG-CoA reductase inhibitors is increased with concomitant use of fenofibrates, caution should be used when prescribing fenofibrates with CRESTOR [seeWarnings and Precautions (5.1) andClinical Pharmacology (12.3)]","ncit:negative","ncit:Qualitative","When CRESTOR was coadministered with fenofibrate, no clinically significant increase in the AUC of rosuvastatin or fenofibrate was observed.","rosuvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"fenofibrate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 15:54:45 -0700","drug-drug-interaction","evidence-challenges","Coumarin Anticoagulants: In a small clinical trial in which lovastatin was administered to warfarin treated patients, no effect on prothrombin time was detected. However, another HMG‑CoA reductase inhibitor has been found to produce a less than two-second increase in prothrombin time in healthy volunteers receiving low doses of warfarin. Also, bleeding and/or increased prothrombin time have been reported in a few patients taking coumarin anticoagulants concomitantly with lovastatin. ","ncit:negative","ncit:Qualitative","Concomitant lovastatin and warfarin did not effect prothrombin time. But bleeding and increased prothrombin time have been reported with lovastatin and warfarin.","warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","lovastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:47:42 -0700","DDI-clinical-trial","evidence-supports","Fluconazole (moderate CYP3A4 inhibitor): Single-dose rivaroxaban AUC and Cmax increased by 40% and 30%, respectively.","ncit:positive","ncit:quantitative",,"rivaroxaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","Fluconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","40","Percent","Increase","UNK","UNK","UNK","30","Percent","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 12:34:19 -0700","drug-drug-interaction","evidence-challenges","Single doses of cimetidine (800 mg) or aluminum- and magnesium-containing antacids did not affect the oral bioavailability of olanzapine. ","ncit:negative","ncit:Qualitative","did not affect the oral bioavailability","olanzapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 16:04:29 -0700","drug-drug-interaction","evidence-challenges","In clinical studies exploring CYP3A4, CYP2C9, P-gp and other pathways, dabigatran did not meaningfully alter the pharmacokinetics of amiodarone, atorvastatin, clarithromycin, diclofenac, clopidogrel, digoxin, pantoprazole, or ranitidine.","ncit:negative","ncit:Qualitative","dabigatran did not meaningfully alter the pharmacokinetics of amiodarone","amiodarone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e1e5249-1cb7-4cc2-ad5a-cdeeee2f494f.html","2016-02-16 18:57:43 -0500","DDI-clinical-trial","evidence-supports","Coadministration of quetiapine and phenytoin, a CYP3A4 inducer increased the mean oral clearance of quetiapine by 5-fold.","ncit:positive","ncit:quantitative",,"quetiapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","phenytoin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","5","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4b0700c9-b417-4c3a-b36f-de461e125bd3.html","2015-11-29 13:57:37 -0700","DDI-clinical-trial","evidence-challenges","Furthermore, in a series of clinical drug interaction studies, coadministration of BRINTELLIX with substrates for CYP2B6 (e.g., bupropion), CYP2C9 (e.g., warfarin), and CYP2C19 (e.g., diazepam), had no clinical meaningful effect on the pharmacokinetics of these substrates (Figure 2).","ncit:negative","ncit:quantitative",,"BRINTELLIX","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4b0700c9-b417-4c3a-b36f-de461e125bd3.html","2015-11-29 13:57:37 -0700","DDI-clinical-trial","evidence-challenges","Furthermore, in a series of clinical drug interaction studies, coadministration of BRINTELLIX with substrates for CYP2B6 (e.g., bupropion), CYP2C9 (e.g., warfarin), and CYP2C19 (e.g., diazepam), had no clinical meaningful effect on the pharmacokinetics of these substrates (Figure 2)","ncit:negative","ncit:quantitative",,"diazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","BRINTELLIX","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 14:04:43 -0400","drug-drug-interaction","evidence-challenges","In studies conducted in healthy subjects, apixaban did not meaningfully alter the pharmacokinetics of digoxin, naproxen, atenolol, prasugrel, or acetylsalicylic acid.","ncit:negative","ncit:Qualitative","pixaban did not meaningfully alter the pharmacokinetics of prasugrel","apixaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"prasugrel","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/9c4bedb4-2d59-4fcd-aad7-fce988cd96d8.html","2016-02-29 14:40:02 -0700","drug-drug-interaction","evidence-supports","Concurrent administration of propranolol (100 to 800 mg daily) has been reported to produce increases in plasma levels of thioridazine (approximately 50% to 400%) and its metabolites (approximately 80% to 300%). Propranolol and thioridazine should not be coadministered.","ncit:positive","ncit:Qualitative","increases in plasma levels of thioridazine (approximately 50% to 400%) and its metabolites (approximately 80% to 300%)","thioridazine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Propranolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 14:55:51 -0700","DDI-clinical-trial","evidence-supports","Rifampin: Rifampin 600 mg once daily for 7 days followed by a single dose of dabigatran decreased its AUC and Cmax by 66% and 67%, respectively. By Day 7 after cessation of rifampin treatment, dabigatran exposure was close to normal [see Warnings and Precautions (5.5) and Drug Interactions (7)].","ncit:positive","ncit:quantitative",,"dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","rifampin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","SD","Oral","1","QD","Oral","7","UNK","66","Percent","Decrease","UNK","UNK","UNK","67","Percent","Decrease","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e1e5249-1cb7-4cc2-ad5a-cdeeee2f494f.html","2016-02-16 16:45:41 -0700","drug-drug-interaction","evidence-supports","Quetiapine exposure is increased by the prototype CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.). and decreased by the prototype CYP3A4 inducers (e..g, phenytoin, carbamazepine, rifampin, avasimibe, St. John’s wort etc.).","ncit:positive","ncit:Qualitative","quetiapine exposure is decreased by CYP3A4 inducers","phenytoin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"Quetiapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 10:52:47 -0800","DDI-clinical-trial","evidence-challenges","Lithium – In 13 healthy subjects the coadministration of nefazodone (200 mg BID) with lithium (500 mg BID) for 5 days (steady-state conditions) was found to be well tolerated. When the two drugs were coadministered, there were no changes in the steady-state pharmacokinetics of either lithium, nefazodone, or its metabolite HO-NEF; however, there were small decreases in the steady-state plasma concentrations of two nefazodone metabolites, mCPP and triazole-dione, which are considered not to be of clinical significance. Therefore, no dosage adjustment of either lithium or nefazodone is required when they are coadministered.","ncit:negative","ncit:quantitative",,"HO-NEF","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","200","Lithium","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","500","BID","Oral","5","BID","Oral","5","13","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 14:27:03 -0800","DDI-clinical-trial","evidence-challenges","When fluoxetine (20 mg QD) and nefazodone (200 mg BID) were administered at steady state there were no changes in the pharmacokinetic parameters for fluoxetine or its metabolite, norfluoxetine. Similarly, there were no changes in the pharmacokinetic parameters of nefazodone or HO-NEF; however, the mean AUC levels of the nefazodone metabolites mCPP and triazole-dione increased by 3 to 6 fold and 1.3 fold, respectively.","ncit:negative","ncit:quantitative",,"nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","200","fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","BID","Oral","UNK","QD","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 12:04:34 -0800","DDI-clinical-trial","evidence-supports","HMG-CoA Reductase Inhibitors – When single 40 mg doses of simvastatin or atorvastatin, both substrates of CYP3A4, were given to healthy adult volunteers who had received nefazodone hydrochloride, 200 mg BID for 6 days, approximately 20 fold increases in plasma concentrations of simvastatin and simvastatin acid and 3 to 4 fold increases in plasma concentrations of atorvastatin and atorvastatin lactone were seen. These effects appear to be due to the inhibition of CYP3A4 by nefazodone because, in the same study, nefazodone had no significant effect on the plasma concentrations of pravastatin, which is not metabolized by CYP3A4 to a clinically significant extent","ncit:positive","ncit:quantitative","entered plasma concentration as AUC","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","atorvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","40","SD","Oral","1","BID","Oral","6","UNK","3 to 4","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:11:14 -0800","DDI-clinical-trial","evidence-challenges","When nefazodone (200 mg BID) was given to patients being treated with theophylline (600 to 1200 mg/day) for chronic obstructive pulmonary disease, there was no change in the steady-state pharmacokinetics of either nefazodone or theophylline. FEV1 measurements taken when theophylline and nefazodone were coadministered did not differ from baseline dosage (i.e., when theophylline was administered alone). Therefore, dosage adjustment is not necessary for either drug when coadministered.","ncit:negative","ncit:quantitative",,"nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","200","theophylline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","600 to 1200","BID","Oral","UNK","Daily","Oral","UNK","UNK","UNK","UNK","UNK","UNKUNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 15:02:14 -0700","DDI-clinical-trial","evidence-supports","Dronedarone: Simultaneous administration of dabigatran etexilate and dronedarone (administered once or twice daily) increases exposure to dabigatran by 70 to 140% compared to dabigatran alone. The increase in exposure is only 30 to 60% higher compared to dabigatran alone when dronedarone is administered 2 hours after dabigatran etexilate","ncit:positive","ncit:quantitative","The increase in exposure is only 30 to 60% higher compared to dabigatran alone when dronedarone is administered 2 hours after dabigatran etexilate","dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","dronedarone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","70-1470-140","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:40:35 -0700","DDI-clinical-trial","evidence-challenges","Following five consecutive nightly doses at bedtime of oral zolpidem tartrate 10 mg in the presence of sertraline 50 mg (17 consecutive daily doses, at 7:00 am, in healthy female volunteers), zolpidem Cmax was significantly higher (43%) and Tmax was significantly decreased (-53%). Pharmacokinetics of sertraline and N-desmethylsertraline were unaffected by zolpidem.","ncit:negative","ncit:quantitative","Pharmacokinetics of sertraline and N-desmethylsertraline were unaffected by zolpidem.","zolpidem","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","10","N-desmethylsertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","50","QD","Oral","17","QD","Oral","5","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:37:36 -0800","DDI-clinical-trial","evidence-supports","Propranolol – The coadministration of nefazodone (200 mg BID) and propranolol (40 mg BID) for 5.5 days to healthy male volunteers (n = 18), including 3 poor and 15 extensive CYP2D6 metabolizers, resulted in 30% and 14% reductions in Cmax and AUC of propranolol, respectively, and a 14% reduction in Cmax for the metabolite, 4-hydroxypropranolol.","ncit:positive","ncit:quantitative",,"nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","propranolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","40","BID","Oral","5.5","BID","Oral","5.5","18","14","Percent","Decrease","UNK","UNK","UNK","30","Percent","Decrease","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 12:04:34 -0800","DDI-clinical-trial","evidence-supports","HMG-CoA Reductase Inhibitors – When single 40 mg doses of simvastatin or atorvastatin, both substrates of CYP3A4, were given to healthy adult volunteers who had received nefazodone hydrochloride, 200 mg BID for 6 days, approximately 20 fold increases in plasma concentrations of simvastatin and simvastatin acid and 3 to 4 fold increases in plasma concentrations of atorvastatin and atorvastatin lactone were seen. These effects appear to be due to the inhibition of CYP3A4 by nefazodone because, in the same study, nefazodone had no significant effect on the plasma concentrations of pravastatin, which is not metabolized by CYP3A4 to a clinically significant extent","ncit:positive","ncit:quantitative","entered plasma concentration as AUC","simvastatin acid","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","200","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","BID","Oral","6","SD","Oral","1","UNK","20","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:39:55 -0700","drug-drug-interaction","evidence-supports","Concomitant treatment with CLOZARIL and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology (12.3)]. Use caution and monitor patients closely when using such inhibitors. Consider reducing the CLOZARIL dose [see Dosage and Administration (2.6)].","ncit:positive","ncit:Qualitative","Erythromycin can increase clozapine levels","erythromycin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"clozapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:43:01 -0700","drug-drug-interaction","evidence-supports","Concomitant treatment with CLOZARIL and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology (12.3)]. Use caution and monitor patients closely when using such inhibitors. Consider reducing the CLOZARIL dose [see Dosage and Administration (2.6)]","ncit:positive","ncit:Qualitative","Duloxetine can increase clozapine levels","clozapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","duloxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/39a5dae2-49f7-4662-9eac-aa7b4c7807a4.html","2016-05-09 16:39:00 -0700","DDI-clinical-trial","evidence-challenges","Digoxin: A single dose of eszopiclone 3 mg did not affect the pharmacokinetics of digoxin measured at steady state following dosing of 0.5 mg twice daily for one day and 0.25 mg daily for the next 6 days. ","ncit:negative","ncit:quantitative","digoxin dosing of 0.5 mg twice daily for one day and 0.25 mg daily for the next 6 days","digoxin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction",".25","eszopiclone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","3","Daily","Oral","6","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:30:14 -0700","DDI-clinical-trial","evidence-supports","After multiple doses of zolpidem tartrate and fluoxetine an increase in the zolpidem half-life (17%) was observed. There was no evidence of an additive effect in psychomotor performance [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:quantitative",,"fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","zolpidem","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","17","Percent","Increase" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 14:07:38 -0800","DDI-clinical-trial","evidence-supports","With 5 mg BID doses of buspirone, slight increases in AUC were observed for nefazodone (23%) and its metabolites hydroxynefazodone (17%) and mCPP (9%)","ncit:positive","ncit:quantitative",,"mCPP","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","250","buspirone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","5","BID","Oral","UNK","BID","Oral","UNK","UNK","9","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 15:52:59 -0700","DDI-clinical-trial","evidence-supports","when ticagrelor 180 mg was given 2 hours after dabigatran, the AUCτ,ss and Cmax,ss of dabigatran increased by only 27% and 24%, respectively [see Warnings and Precautions (5.2) and Drug Interactions (7.1)].","ncit:positive","ncit:quantitative","ticagrlor given 2 hours after dabigatran resulted in less of AUC and CMAX increases than concomitant dosing","dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","ticagrelor","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","180","UNK","Oral","UNK","SD","Oral","1","UNK","27","Percent","Increase","UNK","UNK","UNK","24","Percent","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:51:56 -0700","DDI-clinical-trial","evidence-supports","In a drug interaction study, coadministration of XARELTO (20 mg single dose with food) with a drug that is a combined P-gp and strong CYP3A4 inducer (rifampicin titrated up to 600 mg once daily) led to an approximate decrease of 50% and 22% in AUC and Cmax, respectively. Similar decreases in pharmacodynamic effects were also observed. These decreases in exposure to rivaroxaban may decrease efficacy.","ncit:positive","ncit:quantitative",,"rivaroxaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","20","rifampicin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","SD","Oral","1","QD","Oral","UNK","UNK","50","Percent","Decrease","UNK","UNK","UNK","22","Percent","Decrease","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 13:24:14 -0800","DDI-clinical-trial","evidence-supports","Haloperidol – When a single oral 5 mg dose of haloperidol was coadministered with nefazodone (200 mg BID) at steady state, haloperidol apparent clearance decreased by 35% with no significant increase in peak haloperidol plasma concentrations or time of peak.","ncit:positive","ncit:quantitative",,"nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","haloperidol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","5","SD","Oral","1","BID","Oral","UNK","UNK","UNK","UNK","UNK","35","Percent","Decrease","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4b0700c9-b417-4c3a-b36f-de461e125bd3.html","2015-11-29 13:42:04 -0700","DDI-clinical-trial","evidence-challenges","Following coadministration of stable doses of warfarin (1 to 10 mg/day) with multiple daily doses of BRINTELLIX, no significant effects were observed in INR, prothrombin values or total warfarin (protein bound plus free drug) pharmacokinetics for both R- and S-warfarin [see Drug Interactions (7.4)].","ncit:negative","ncit:quantitative",,"BRINTELLIX","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","1 to 10","Daily","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/036db1f2-52b3-42a0-acf9-817b7ba8c724.html","2015-12-08 18:57:19 -0700","DDI-clinical-trial","evidence-challenges","In vivo studies have revealed no effect of ziprasidone on the pharmacokinetics of estrogen or progesterone components. Ziprasidone at a dose of 20 mg twice daily did not affect the pharmacokinetics of concomitantly administered oral contraceptives, ethinyl estradiol (0.03 mg) and levonorgestrel (0.15 mg).","ncit:negative","ncit:quantitative",,"levonorgestrel","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction",".15","Ziprasidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","UNK","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/9c4bedb4-2d59-4fcd-aad7-fce988cd96d8.html","2016-02-29 16:44:38 -0500","drug-drug-interaction","evidence-supports","Concurrent administration of pindolol and thioridazine have resulted in moderate, dose related increases in the serum levels of thioridazine and two of its metabolites, as well as higher than expected serum pindolol levels. Pindolol and thioridazine should not be coadministered.","ncit:positive","ncit:Qualitative","concomitant use with thirodazine produced higher than expected serum pindolol levels.","pindolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","thioridazine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 14:04:43 -0400","drug-drug-interaction","evidence-challenges","In studies conducted in healthy subjects, apixaban did not meaningfully alter the pharmacokinetics of digoxin, naproxen, atenolol, prasugrel, or acetylsalicylic acid.","ncit:negative","ncit:Qualitative","pixaban did not meaningfully alter the pharmacokinetics of acetylsalicylic acid","acetylsalicylic acid","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","apixaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:39:55 -0700","drug-drug-interaction","evidence-supports","Concomitant treatment with CLOZARIL and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology (12.3)]. Use caution and monitor patients closely when using such inhibitors. Consider reducing the CLOZARIL dose [see Dosage and Administration (2.6)]. ","ncit:positive","ncit:Qualitative","cimetidine can increase clozapine levels","cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"clozapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5429f134-839f-4ffc-9944-55f51238def8.html","2015-12-18 13:50:52 -0700","DDI-clinical-trial","evidence-supports","SAPHRIS may enhance the inhibitory effects of paroxetine on its own metabolism. Concomitant use of paroxetine with SAPHRIS increased the paroxetine exposure by 2-fold as compared to use paroxetine alone [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:quantitative",,"SAPHRIS","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","2","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/7b8e5b26-b9e4-4704-921b-3c3c0d159916.html","2015-11-29 16:14:39 -0700","DDI-clinical-trial","evidence-challenges","In a drug interaction study, co-administration of INVEGA® (12 mg once daily for 5 days) with divalproex sodium extended-release tablets (500 mg to 2000 mg once daily) did not affect the steady-state pharmacokinetics (AUC24h and Cmax,ss) of valproate in 13 patients stabilized on valproate. ","ncit:negative","ncit:quantitative",,"divalproex sodium","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","500 to 2000","INVEGA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","12","QD","Oral","UNK","QD","Oral","5","13","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 16:00:33 -0700","drug-drug-interaction","evidence-challenges","Diclofenac, Ranitidine, and Digoxin: None of these drugs alters exposure to dabigatran.","ncit:negative","ncit:Qualitative","ranitidine does not alter exposure to dabigatran.","dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Ranitidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 17:30:22 -0700","DDI-clinical-trial","evidence-challenges","Imipramine: Coadministration of single doses of Zaleplon 20 mg and imipramine 75 mg produced additive effects on decreased alertness and impaired psychomotor performance for 2 to 4 hours after administration. The interaction was pharmacodynamic with no alteration of the pharmacokinetics of either drug.","ncit:negative","ncit:quantitative","with no alteration of the pharmacokinetics of either drug.","imipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","75","Zaleplon","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","20","SD","Oral","1","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:41:56 -0700","drug-drug-interaction","evidence-supports","Concomitant treatment with CLOZARIL and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology (12.3)]. Use caution and monitor patients closely when using such inhibitors. Consider reducing the CLOZARIL dose [see Dosage and Administration (2.6)]","ncit:positive","ncit:Qualitative","Bupropion can increase clozapine levels","bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"clozapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-31 12:57:26 -0700","drug-drug-interaction","evidence-challenges","Data from drug-drug interactions studies involving coadministration of gemfibrozil, niacin, itraconazole, erythromycin, tolbutamide or clopidogrel indicate that the PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with any of these drugs.","ncit:negative","ncit:Qualitative","PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with clopidogrel","clopidogrel","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"fluvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 16:24:02 -0700","DDI-clinical-trial","evidence-challenges","Olanzapine did not influence the pharmacokinetics of diazepam or its active metabolite N-desmethyldiazepam.","ncit:negative","ncit:quantitative",,"N-desmethyldiazepam.","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","UNK","Olanzapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:38:58 -0700","DDI-clinical-trial","evidence-challenges","Following five consecutive nightly doses at bedtime of oral zolpidem tartrate 10 mg in the presence of sertraline 50 mg (17 consecutive daily doses, at 7:00 am, in healthy female volunteers), zolpidem Cmax was significantly higher (43%) and Tmax was significantly decreased (-53%). Pharmacokinetics of sertraline and N-desmethylsertraline were unaffected by zolpidem.","ncit:negative","ncit:quantitative","Pharmacokinetics of sertraline and N-desmethylsertraline were unaffected by zolpidem.","zolpidem","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","10","sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","50","QD","Oral","1","QD","Oral","5","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-30 15:08:21 -0700","drug-drug-interaction","evidence-supports","Concomitant administration of fluvastatin and glyburide increased glyburide exposures. Patients on concomitant therapy of glyburide and fluvastatin should continue to be monitored appropriately [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative","Concomitant fluvastatin increases glyburide exposure. Details in Section 12 Table 3","glyburide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/036db1f2-52b3-42a0-acf9-817b7ba8c724.html","2015-12-08 18:44:10 -0700","DDI-clinical-trial","evidence-supports","Carbamazepine is an inducer of CYP3A4; administration of 200 mg twice daily for 21 days resulted in a decrease of approximately 35% in the AUC of ziprasidone. This effect may be greater when higher doses of carbamazepine are administered. ","ncit:positive","ncit:quantitative",,"carbamazepine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","ziprasidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","BID","Oral","21","UNK","35","Percent","Decrease","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/39a5dae2-49f7-4662-9eac-aa7b4c7807a4.html","2016-05-09 16:27:24 -0700","DDI-clinical-trial","evidence-challenges","Paroxetine: Coadministration of single dose of eszopiclone and paroxetine produced no pharmacokinetic or pharmacodynamic interaction. The lack of a drug interaction following single-dose administration does not predict the complete absence of a pharmacodynamic effect following chronic administration. ","ncit:negative","ncit:quantitative","Coadministration of single dose of eszopiclone and paroxetine produced no pharmacokinetic or pharmacodynamic interaction.","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","eszopiclone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","SD","Oral","1","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1fd0ba23-962e-427f-8b9d-2cf8f64d0f95.html","2016-03-31 11:20:38 -0700","drug-drug-interaction","evidence-supports","Gemfibrozil significantly increased rosuvastatin exposure. Due to an observed increased risk of myopathy/rhabdomyolysis, combination therapy with CRESTOR and gemfibrozil should be avoided. If used together, the dose of CRESTOR should not exceed 10 mg once daily [seeClinical Pharmacology (12.3)]","ncit:positive","ncit:Qualitative","Gemfibrozil significantly increased rosuvastatin exposure. Study details in Section 12 Table 4","gemfibrozil","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"rosuvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 11:01:28 -0700","drug-drug-interaction","evidence-challenges","In dedicated studies conducted in healthy subjects, famotidine, atenolol, prasugrel, and enoxaparin did not meaningfully alter the pharmacokinetics of apixaban.","ncit:negative","ncit:Qualitative","prasugrel did not meaningfully alter the pharmacokinetics of apixaban","apixaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","prasugrel","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 19:19:02 -0400","drug-drug-interaction","evidence-supports","Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin. (See CONTRAINDICATIONS, WARNINGS, Myopathy/Rhabdomyolysis, and CLINICAL PHARMACOLOGY, Pharmacokinetics.)","ncit:positive","ncit:Qualitative","Erythromycin is a strong inhibitor of CYP3A4 and reduces the elimination of lovastatin","erythromycin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"lovastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 16:13:29 -0700","drug-drug-interaction","evidence-supports","Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin. (See CONTRAINDICATIONS, WARNINGS, Myopathy/Rhabdomyolysis, and CLINICAL PHARMACOLOGY, Pharmacokinetics.)","ncit:positive","ncit:Qualitative","voriconazole is a strong inhibitor of CYP3A4 and reduces the elimination of lovastatin","lovastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","voriconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/036db1f2-52b3-42a0-acf9-817b7ba8c724.html","2015-12-08 18:50:07 -0700","DDI-clinical-trial","evidence-challenges","Cimetidine at a dose of 800 mg QD for 2 days did not affect ziprasidone pharmacokinetics.","ncit:negative","ncit:quantitative",,"ziprasidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","Cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","800","UNK","Oral","UNK","QD","Oral","2","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2015-12-18 15:38:03 -0700","DDI-clinical-trial","evidence-supports","A pharmacokinetic study was conducted in 16 schizophrenic patients who received clozapine under steady-state conditions. After coadministration of fluvoxamine for 14 days, mean trough concentrations of clozapine and its metabolites, N-desmethylclozapine and clozapine N-oxide, were elevated about 3-fold compared to baseline steady-state concentrations.","ncit:positive","ncit:quantitative",,"fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","N-desmethylclozapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","UNK","UNK","UNK","UNK","UNK","Oral","14","16","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/fdbfe194-b845-42c5-bb87-a48118bc72e7.html","2016-03-31 11:53:44 -0700","DDI-clinical-trial","evidence-supports","Coadministration of simvastatin (40 mg QD for 10 days) resulted in an increase in the maximum mean levels of cardioactive digoxin (given as a single 0.4 mg dose on day 10) by approximately 0.3 ng/mL.","ncit:positive","ncit:quantitative",,"simvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","digoxin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction",".4","SD","Oral","1","QD","Oral","10","UNK","UNK","UNK","UNK","UNK","UNK","UNK",".3ng//mL","UNK","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/036db1f2-52b3-42a0-acf9-817b7ba8c724.html","2015-12-08 18:55:35 -0700","DDI-clinical-trial","evidence-challenges","In vivo studies have revealed no effect of ziprasidone on the pharmacokinetics of estrogen or progesterone components. Ziprasidone at a dose of 20 mg twice daily did not affect the pharmacokinetics of concomitantly administered oral contraceptives, ethinyl estradiol (0.03 mg) and levonorgestrel (0.15 mg).","ncit:negative","ncit:quantitative",,"ethinyl estradiol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction",".03","ziprasidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","UNK","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:45:30 -0700","DDI-clinical-trial","evidence-challenges","A single-dose interaction study with zolpidem tartrate 10 mg and fluoxetine 20 mg at steady-state levels in male volunteers did not demonstrate any clinically significant pharmacokinetic or pharmacodynamic interactions. ","ncit:negative","ncit:quantitative","id not demonstrate any clinically significant pharmacokinetic or pharmacodynamic interactions","zolpidem","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","10","fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 15:56:19 -0700","drug-drug-interaction","evidence-challenges","Propranolol: In normal volunteers, there was no clinically significant pharmacokinetic or pharmacodynamic interaction with concomitant administration of single doses of lovastatin and propranolol.","ncit:negative","ncit:Qualitative","No clinically significant PK interaction with concomitant lovastatin and propranolol","propranolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","lovastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 16:07:41 -0700","drug-drug-interaction","evidence-challenges","In clinical studies exploring CYP3A4, CYP2C9, P-gp and other pathways, dabigatran did not meaningfully alter the pharmacokinetics of amiodarone, atorvastatin, clarithromycin, diclofenac, clopidogrel, digoxin, pantoprazole, or ranitidine.","ncit:negative","ncit:Qualitative","dabigatran did not meaningfully alter the pharmacokinetics of digoxin","dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"digoxin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 15:45:57 -0700","DDI-clinical-trial","evidence-supports","Ticagrelor: Administration of ticagrelor modestly increases plasma concentrations of dabigatran with the magnitude of increase dependent on the dose and timing of ticagrelor administration. When dabigatran etexilate 110 mg twice daily was coadministered with 90 mg oral ticagrelor twice daily, the AUCτ,ss and Cmax,ss of dabigatran increased by 26% and 29%, respectively.","ncit:positive","ncit:quantitative",,"ticagrelor","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","90","dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","110","BID","Oral","UNK","BID","Oral","UNK","UNK","26","Percent","Increase","UNK","UNK","UNK","29","Percent","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a0da0dba-a56d-486b-a45b-e8a7cdfbeac6.html","2016-05-10 10:40:54 -0700","DDI-clinical-trial","evidence-supports","Coadministration of oral contraceptives increased maximum plasma concentration by 6%, decreased clearance by 32%, and increased half-life by 16%. Grapefruit juice Coadministration of grapefruit juice increased the maximum plasma concentration of triazolam","ncit:positive","ncit:quantitative",,"oral contraceptives","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","triazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","UNK","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","32","Percent","Decrease","6","Percent","Increase","16","Percent","Increase" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ee49f3b1-1650-47ff-9fb1-ea53fe0b92b6.html","2016-03-14 13:58:35 -0700","DDI-clinical-trial","evidence-challenges","The effects of ABILIFY on the exposures of other drugs are summarized in Figure 21. A population PK analysis in patients with major depressive disorder showed no substantial change in plasma concentrations of fluoxetine (20 mg/day or 40 mg/day), paroxetine CR (37.5 mg/day or 50 mg/day), or sertraline (100 mg/day or 150 mg/day) dosed to steady-state. The steady-state plasma concentrations of fluoxetine and norfluoxetine increased by about 18% and 36%, respectively, and concentrations of paroxetine decreased by about 27%. The steady-state plasma concentrations of sertraline and desmethylsertraline were not substantially changed when these antidepressant therapies were coadministered with aripiprazole.","ncit:negative","ncit:quantitative","The steady-state plasma concentrations of sertraline and desmethylsertraline were not substantially changed when these antidepressant therapies were coadministered with aripiprazole.","ABILIFY","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","100-150","Daily","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 15:37:23 -0700","drug-drug-interaction","evidence-challenges","Clarithromycin: Coadministered clarithromycin had no impact on the exposure to dabigatran.","ncit:negative","ncit:Qualitative","clarithromycin had no impact on the exposure to dabigatran","dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","clarithromycin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 16:15:09 -0700","drug-drug-interaction","evidence-supports","Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin. (See CONTRAINDICATIONS, WARNINGS, Myopathy/Rhabdomyolysis, and CLINICAL PHARMACOLOGY, Pharmacokinetics.)","ncit:positive","ncit:Qualitative","Boceprevir is a strong inhibitor of CYP3A4 and reduces the elimination of lovastatin","lovastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","boceprevir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 10:46:00 -0800","DDI-clinical-trial","evidence-supports","There were also no changes in the pharmacokinetics of nefazodone or its triazole-dione metabolite, but the AUC and Cmax of mCPP increased by 44% and 48%, respectively, while the AUC of HO-NEF decreased by 19%. No changes in doses of either nefazodone or desipramine are necessary when the two drugs are given concomitantly. Subsequent dose adjustments should be made on the basis of clinical response.","ncit:positive","ncit:quantitative",,"desipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","75","mCPP","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","150","BID","Oral","UNK","QD","Oral","UNK","UNK","44","Percent","Increase","UNK","UNK","UNK","48","Percent","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 12:46:01 -0700","drug-drug-interaction","evidence-supports"," Omeprazole and rifampin may cause an increase in olanzapine clearance. ","ncit:positive","ncit:Qualitative","may cause an increase in olanzapine clearance","olanzapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","rifampin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-31 12:55:20 -0700","drug-drug-interaction","evidence-challenges","Data from drug-drug interactions studies involving coadministration of gemfibrozil, niacin, itraconazole, erythromycin, tolbutamide or clopidogrel indicate that the PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with any of these drugs.","ncit:negative","ncit:Qualitative","PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with niacin","fluvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","niacin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 18:16:48 -0700","DDI-clinical-trial","evidence-challenges","Warfarin: Multiple oral doses of Zaleplon (20 mg q24h for 13 days) did not affect the pharmacokinetics of warfarin (R+)- or (S-)-enantiomers or the pharmacodynamics (prothrombin time) following a single 25-mg oral dose of warfarin.","ncit:negative","ncit:quantitative","did not affect the pharmacokinetics of warfarin","Zaleplon","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","25","SD","Oral","1","QD","UNK","13","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/9c4bedb4-2d59-4fcd-aad7-fce988cd96d8.html","2016-02-29 14:22:02 -0700","drug-drug-interaction","evidence-supports","Reduced cytochrome P450 2D6 isozyme activity drugs that inhibit this isozyme (e.g., fluoxetine and paroxetine) and certain other drugs (e.g., fluvoxamine, propranolol, and pindolol) appear to appreciably inhibit the metabolism of thioridazine. The resulting elevated levels of thioridazine would be expected to augment the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as Torsades de pointes type arrhythmias.","ncit:positive","ncit:Qualitative","appear to appreciably inhibit the metabolism of thioridazine and result in elevated levels of thioridazine","propranolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"thioridazine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5429f134-839f-4ffc-9944-55f51238def8.html","2015-12-18 13:50:52 -0700","DDI-clinical-trial","evidence-supports","SAPHRIS is metabolized by CYP1A2. Marginal increase of asenapine exposure was observed when SAPHRIS is used with fluvoxamine at 25 mg administered twice daily [see Clinical Pharmacology (12.3)","ncit:positive","ncit:quantitative","Marginal increase of asenapine exposure","SAPHRIS","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","25","UNK","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c6e131fe-e7df-4876-83f7-9156fc4e8228.html","2016-03-14 15:02:19 -0700","DDI-clinical-trial","evidence-supports","When multiple doses of LIPITOR and digoxin were co-administered, steady state plasma digoxin concentrations increased by approximately 20%. Patients taking digoxin should be monitored appropriately","ncit:positive","ncit:quantitative",,"digoxin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","LIPITOR","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","20","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 17:46:48 -0700","DDI-clinical-trial","evidence-challenges","Venlafaxine: Coadministration of a single dose of zaleplon 10 mg and multiple doses of venlafaxine ER (extended release) 150 mg did not result in any significant changes in the pharmacokinetics of either zaleplon or venlafaxine. In addition, there was no pharmacodynamic interaction as a result of coadministration of zaleplon and venlafaxine ER.","ncit:negative","ncit:quantitative","did not result in any significant changes in the pharmacokinetics of either zaleplon or venlafaxine","venlafaxine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","150","zaleplon","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","10","SD","Oral","1","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:09:54 -0800","DDI-clinical-trial","evidence-challenges","When nefazodone (200 mg BID) was given to patients being treated with theophylline (600 to 1200 mg/day) for chronic obstructive pulmonary disease, there was no change in the steady-state pharmacokinetics of either nefazodone or theophylline. FEV1 measurements taken when theophylline and nefazodone were coadministered did not differ from baseline dosage (i.e., when theophylline was administered alone). Therefore, dosage adjustment is not necessary for either drug when coadministered.","ncit:negative","ncit:quantitative",,"theophylline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","600 to 1200","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","Daily","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 13:18:12 -0700","DDI-clinical-trial","evidence-challenges","Multiple doses of olanzapine (10 mg for 8 days) did not influence the kinetics of lithium. ","ncit:negative","ncit:quantitative",,"lithium.","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","olanzapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","10","UNK","Oral","UNK","UNK","Oral","8","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:23:33 -0800","DDI-clinical-trial","evidence-supports","Digoxin – When nefazodone (200 mg BID) and digoxin (0.2 mg QD) were coadministered for 9 days to healthy male volunteers (n = 18) who were phenotyped as CYP2D6 extensive metabolizers, Cmax, Cmin, and AUC of digoxin were increased by 29%, 27%, and 15%, respectively.","ncit:positive","ncit:quantitative",,"nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","digoxin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction",".2","QD","Oral","9","BID","Oral","9","18","15","Percent","Increase","UNK","UNK","UNK","29","Percent","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c6e131fe-e7df-4876-83f7-9156fc4e8228.html","2016-03-14 14:49:42 -0700","drug-drug-interaction","evidence-supports","Atorvastatin AUC was significantly increased with concomitant administration of LIPITOR with several combinations of HIV protease inhibitors, as well as with the hepatitis C protease inhibitor telaprevir, compared to that of LIPITOR alone [","ncit:positive","ncit:Qualitative","Atorvastatin AUC was significantly increased with concomitant administration","Atorvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","telaprevir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/9c4bedb4-2d59-4fcd-aad7-fce988cd96d8.html","2016-02-29 14:22:02 -0700","drug-drug-interaction","evidence-supports","Reduced cytochrome P450 2D6 isozyme activity drugs that inhibit this isozyme (e.g., fluoxetine and paroxetine) and certain other drugs (e.g., fluvoxamine, propranolol, and pindolol) appear to appreciably inhibit the metabolism of thioridazine. The resulting elevated levels of thioridazine would be expected to augment the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as Torsades de pointes type arrhythmias.","ncit:positive","ncit:Qualitative","appear to appreciably inhibit the metabolism of thioridazine and result in elevated levels of thioridazine","pindolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"thioridazine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 21:24:45 -0400","DDI-clinical-trial","evidence-challenges","Ibuprofen: Ibuprofen is known to affect renal function and, consequently, alter the renal excretion of other drugs. There was no apparent pharmacokinetic interaction between zaleplon and ibuprofen following single dose administration (10 mg and 600 mg, respectively) of each drug. This was expected because zaleplon is primarily metabolized and renal excretion of unchanged zaleplon accounts for less than 1% of the administered dose. ","ncit:negative","ncit:quantitative","no apparent pharmacokinetic interaction","zaleplon","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","10","ibuprofen","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","600","SD","Oral","1","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 18:01:31 -0700","DDI-clinical-trial","evidence-supports","Rifampin: CYP3A4 is ordinarily a minor metabolizing enzyme of zaleplon. Multiple-dose administration of the potent CYP3A4 inducer rifampin (600 mg every 24 hours, q24h, for 14 days), however, reduced zaleplon Cmax and AUC by approximately 80%.","ncit:positive","ncit:quantitative",,"zaleplon","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","rifampin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","UNK","Oral","UNK","QD","Oral","14","UNK","80","Percent","Decrease","UNK","UNK","UNK","80","Percent","Decrease","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c6e131fe-e7df-4876-83f7-9156fc4e8228.html","2016-03-14 14:46:09 -0700","DDI-clinical-trial","evidence-supports","Clarithromycin: Atorvastatin AUC was significantly increased with concomitant administration of LIPITOR 80 mg with clarithromycin (500 mg twice daily) compared to that of LIPITOR alone [see Clinical Pharmacology (12.3)]. Therefore, in patients taking clarithromycin, caution should be used when the LIPITOR dose exceeds 20 mg [see Warnings and Precautions, Skeletal Muscle (5.1) and Dosage and Administration (2.6)]. ","ncit:positive","ncit:quantitative","Atorvastatin AUC was significantly increased with concomitant administration of LIPITOR 80 mg with clarithromycin (500 mg twice daily)","Atorvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","80","clarithromycin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","500","UNK","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 18:26:57 -0500","DDI-clinical-trial","evidence-challenges","Multiple doses of olanzapine did not affect the pharmacokinetics of theophylline or its metabolites. ","ncit:negative","ncit:quantitative",,"theophylline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","olanzapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c6e131fe-e7df-4876-83f7-9156fc4e8228.html","2016-03-14 14:54:30 -0700","DDI-clinical-trial","evidence-supports","Itraconazole: Atorvastatin AUC was significantly increased with concomitant administration of LIPITOR 40 mg and itraconazole 200 mg [see Clinical Pharmacology (12.3)]. Therefore, in patients taking itraconazole, caution should be used when the LIPITOR dose exceeds 20 mg [see Warnings and Precautions, Skeletal Muscle (5.1) and Dosage and Administration (2.6)]. ","ncit:positive","ncit:quantitative","Atorvastatin AUC was significantly increased with concomitant administration of LIPITOR 40 mg and itraconazole 200 mg","itraconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","Atorvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","40","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 11:02:59 -0700","drug-drug-interaction","evidence-challenges","In studies conducted in healthy subjects, apixaban did not meaningfully alter the pharmacokinetics of digoxin, naproxen, atenolol, prasugrel, or acetylsalicylic acid.","ncit:negative","ncit:Qualitative","pixaban did not meaningfully alter the pharmacokinetics of naproxen","apixaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"naproxen","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 14:04:43 -0400","drug-drug-interaction","evidence-challenges","In studies conducted in healthy subjects, apixaban did not meaningfully alter the pharmacokinetics of digoxin, naproxen, atenolol, prasugrel, or acetylsalicylic acid.","ncit:negative","ncit:Qualitative","pixaban did not meaningfully alter the pharmacokinetics of atenolol","atenolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","apixaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:47:05 -0800","DDI-clinical-trial","evidence-challenges","Propranolol – The coadministration of nefazodone (200 mg BID) and propranolol (40 mg BID) for 5.5 days to healthy male volunteers (n = 18), including 3 poor and 15 extensive CYP2D6 metabolizers, resulted in 30% and 14% reductions in Cmax and AUC of propranolol, respectively, and a 14% reduction in Cmax for the metabolite, 4-hydroxypropranolol. The kinetics of nefazodone, hydroxynefazodone, and triazole-dione were not affected by coadministration of propranolol. However, Cmax, Cmin, and AUC of m-chlorophenylpiperazine were increased by 23%, 54%, and 28%, respectively. No change in initial dose of either drug is necessary and dose adjustments should be made on the basis of clinical response.","ncit:negative","ncit:quantitative",,"propranolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","200","BID","Oral","5.5","BID","Oral","5.5","18","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 12:08:12 -0800","DDI-clinical-trial","evidence-challenges","HMG-CoA Reductase Inhibitors – When single 40 mg doses of simvastatin or atorvastatin, both substrates of CYP3A4, were given to healthy adult volunteers who had received nefazodone hydrochloride, 200 mg BID for 6 days, approximately 20 fold increases in plasma concentrations of simvastatin and simvastatin acid and 3 to 4 fold increases in plasma concentrations of atorvastatin and atorvastatin lactone were seen. These effects appear to be due to the inhibition of CYP3A4 by nefazodone because, in the same study, nefazodone had no significant effect on the plasma concentrations of pravastatin, which is not metabolized by CYP3A4 to a clinically significant extent","ncit:negative","ncit:quantitative",,"pravastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","UNK","Oral","UNK","BID","Oral","6","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/7b8e5b26-b9e4-4704-921b-3c3c0d159916.html","2015-11-29 16:15:29 -0700","drug-drug-interaction","evidence-challenges","In a clinical study, subjects on stable doses of valproate had comparable valproate average plasma concentrations when INVEGA® 3–15 mg/day was added to their existing valproate treatment.","ncit:negative","ncit:Qualitative","omparable valproate average plasma concentrations","INVEGA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"valproate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:53:19 -0700","drug-drug-interaction","evidence-challenges","A study involving cimetidine/zolpidem tartrate and ranitidine/zolpidem tartrate combinations revealed no effect of either drug on the pharmacokinetics or pharmacodynamics of zolpidem.","ncit:negative","ncit:Qualitative","no effect of either drug on the pharmacokinetics or pharmacodynamics of zolpidem.","zolpidem","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a971ea18-40cf-4a01-b696-180ccc3fddb5.html","2016-02-29 16:08:19 -0500","drug-drug-interaction","evidence-supports","Concomitant administration of propranolol with phenothiazines results in increased plasma levels of both drugs","ncit:positive","ncit:Qualitative","results in increased plasma levels of both drugs","phenothiazines","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"propranolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ee49f3b1-1650-47ff-9fb1-ea53fe0b92b6.html","2016-03-14 13:55:11 -0700","DDI-clinical-trial","evidence-supports","The effects of ABILIFY on the exposures of other drugs are summarized in Figure 21. A population PK analysis in patients with major depressive disorder showed no substantial change in plasma concentrations of fluoxetine (20 mg/day or 40 mg/day), paroxetine CR (37.5 mg/day or 50 mg/day), or sertraline (100 mg/day or 150 mg/day) dosed to steady-state. The steady-state plasma concentrations of fluoxetine and norfluoxetine increased by about 18% and 36%, respectively, and concentrations of paroxetine decreased by about 27%. The steady-state plasma concentrations of sertraline and desmethylsertraline were not substantially changed when these antidepressant therapies were coadministered with aripiprazole.","ncit:positive","ncit:quantitative","this was a pop pk study","paroxetine CR","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","37.5-50","ABILIFY","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","Daily","Oral","UNK","UNK","Oral","UNK","UNK","27","Percent","Decrease","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:45:30 -0700","DDI-clinical-trial","evidence-supports","When multiple doses of zolpidem and fluoxetine were given at steady state and the concentrations evaluated in healthy females, an increase in the zolpidem half-life (17%) was observed. There was no evidence of an additive effect in psychomotor performance.","ncit:positive","ncit:quantitative","in healthy females","fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","zolpidem","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","UNK","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","17","Percent","Increase" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:53:39 -0700","drug-drug-interaction","evidence-challenges","A study involving cimetidine/zolpidem tartrate and ranitidine/zolpidem tartrate combinations revealed no effect of either drug on the pharmacokinetics or pharmacodynamics of zolpidem.","ncit:negative","ncit:Qualitative","no effect of either drug on the pharmacokinetics or pharmacodynamics of zolpidem.","zolpidem","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","ranitidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/fdbfe194-b845-42c5-bb87-a48118bc72e7.html","2016-03-31 12:23:25 -0700","drug-drug-interaction","evidence-supports","Elevated plasma levels of HMG-CoA reductase inhibitory activity increases the risk of myopathy and rhabdomyolysis, particularly with higher doses of simvastatin. [See Warnings and Precautions (5.1) and Clinical Pharmacology (12.3).] Concomitant use of drugs labeled as having a strong inhibitory effect on CYP3A4 is contraindicated [see Contraindications (4)]. If treatment with itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with simvastatin must be suspended during the course of treatment.","ncit:positive","ncit:Qualitative","strong inhibitor of CYP3A4 may elevate simvastatin plasma level","simvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","erythromycin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/fdbfe194-b845-42c5-bb87-a48118bc72e7.html","2016-03-31 12:38:39 -0700","drug-drug-interaction","evidence-supports","Elevated plasma levels of HMG-CoA reductase inhibitory activity increases the risk of myopathy and rhabdomyolysis, particularly with higher doses of simvastatin. [See Warnings and Precautions (5.1) and Clinical Pharmacology (12.3).] Concomitant use of drugs labeled as having a strong inhibitory effect on CYP3A4 is contraindicated [see Contraindications (4)]. If treatment with itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with simvastatin must be suspended during the course of treatment.","ncit:positive","ncit:Qualitative","strong inhibitor of CYP3A4 may elevate simvastatin plasma level","telithromycin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"simvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/44dcbf97-99ec-427c-ba50-207e0069d6d2.html","2016-03-31 13:20:20 -0400","drug-drug-interaction","evidence-challenges","LIVALO had no significant pharmacokinetic interaction with R- and S- warfarin. LIVALO had no significant effect on prothrombin time (PT) and international normalized ratio (INR) when administered to patients receiving chronic warfarin treatment [see Clinical Pharmacology (12.3)]. However, patients receiving warfarin should have their PT and INR monitored when pitavastatin is added to their therapy. ","ncit:negative","ncit:Qualitative","Pitavastatin had no significant pharmacokinetic interaction with R- and S- warfarin. and no significant effect on prothrombin time (PT) and international normalized ratio (INR) when administered to patients receiving chronic warfarin.Study details in section 12 Table 3","pitavastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 17:37:17 -0700","DDI-clinical-trial","evidence-challenges","Thioridazine: Coadministration of single doses of Zaleplon 20 mg and thioridazine 50 mg produced additive effects on decreased alertness and impaired psychomotor performance for 2 to 4 hours after administration. The interaction was pharmacodynamic with no alteration of the pharmacokinetics of either drug.","ncit:negative","ncit:quantitative","no alteration of the pharmacokinetics of either drug.","Zaleplon","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","thioridazine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","50","SD","UNK","1","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:37:36 -0800","DDI-clinical-trial","evidence-challenges","Digoxin – When nefazodone (200 mg BID) and digoxin (0.2 mg QD) were coadministered for 9 days to healthy male volunteers (n = 18) who were phenotyped as CYP2D6 extensive metabolizers, Cmax, Cmin, and AUC of digoxin were increased by 29%, 27%, and 15%, respectively. Digoxin had no effects on the pharmacokinetics of nefazodone and its active metabolites. Because of the narrow therapeutic index of digoxin, caution should be exercised when nefazodone and digoxin are coadministered; plasma level monitoring for digoxin is recommended.","ncit:negative","ncit:quantitative",,"digoxin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",".2","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","200","BID","Oral","9","QD","Oral","9","18","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/39a5dae2-49f7-4662-9eac-aa7b4c7807a4.html","2016-05-09 16:27:24 -0700","drug-drug-interaction","evidence-challenges"," When eszopiclone was coadministered with olanzapine, no pharmacokinetic interaction was detected in levels of eszopiclone or olanzapine, but a pharmacodynamic interaction was seen on a measure of psychomotor function.","ncit:negative","ncit:Qualitative","eszopiclone was coadministered with olanzapine, no pharmacokinetic interaction was detected in levels of eszopiclone or olanzapine","olanzapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"eszopiclone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 10:50:04 -0700","drug-drug-interaction","evidence-supports","Avoid concomitant use of ELIQUIS with strong dual inducers of CYP3A4 and P-gp (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort) because such drugs will decrease exposure to apixaban [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative","phenytoin will decrease exposure to apixaban","phenytoin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"apixaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/fdbfe194-b845-42c5-bb87-a48118bc72e7.html","2016-03-31 12:22:09 -0700","drug-drug-interaction","evidence-supports","Elevated plasma levels of HMG-CoA reductase inhibitory activity increases the risk of myopathy and rhabdomyolysis, particularly with higher doses of simvastatin. [See Warnings and Precautions (5.1) and Clinical Pharmacology (12.3).] Concomitant use of drugs labeled as having a strong inhibitory effect on CYP3A4 is contraindicated [see Contraindications (4)]. If treatment with itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with simvastatin must be suspended during the course of treatment.","ncit:positive","ncit:Qualitative","strong inhibitor of CYP3A4 may elevate simvastatin plasma level","simvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","itraconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/7b8e5b26-b9e4-4704-921b-3c3c0d159916.html","2015-11-29 18:21:18 -0500","DDI-clinical-trial","evidence-supports","Co-administration of a single dose of INVEGA® 12 mg with divalproex sodium extended-release tablets (two 500 mg tablets once daily) resulted in an increase of approximately 50% in the Cmax and AUC of paliperidone. Dosage reduction for INVEGA® should be considered when INVEGA® is co-administered with valproate after clinical assessment.","ncit:positive","ncit:quantitative",,"INVEGA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","12","divalproex sodium","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","1000","SD","Oral","1","QD","Oral","UNK","UNK","50","Percent","Increase","UNK","UNK","UNK","50","Percent","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:26:31 -0700","drug-drug-interaction","evidence-supports","In drug interaction studies evaluating the concomitant use with drugs that are combined P-gp and CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin, erythromycin and fluconazole), increases in rivaroxaban exposure and pharmacodynamic effects (i.e., factor Xa inhibition and PT prolongation) were observed. The increases in exposure ranged from 30% to 160%. Significant increases in rivaroxaban exposure may increase bleeding risk [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative","increases in rivaroxaban exposure","erythromycin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"rivaroxaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c6e131fe-e7df-4876-83f7-9156fc4e8228.html","2016-03-14 15:04:06 -0700","drug-drug-interaction","evidence-supports","Co-administration of LIPITOR and an oral contraceptive increased AUC values for norethindrone and ethinyl estradiol [see Clinical Pharmacology (12.3)]. These increases should be considered when selecting an oral contraceptive for a woman taking LIPITOR.","ncit:positive","ncit:Qualitative","Co-administration of LIPITOR and an oral contraceptive increased AUC values for norethindrone and ethinyl estradiol","norethindrone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","LIPITOR","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/afad3051-9df2-4c54-9684-e8262a133af8.html","2015-12-08 19:34:38 -0700","DDI-clinical-trial","evidence-challenges","Valproate: It is not necessary to adjust the LATUDA dose when used concomitantly with valproate. A dedicated drug-drug interaction study has not been conducted with valproate and LATUDA. Based on pharmacokinetic data from the bipolar depression studies valproate levels were not affected by lurasidone, and lurasidone concentrations were not affected by valproate. ","ncit:negative","ncit:quantitative",,"lurasidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","valproate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 18:04:06 -0700","DDI-clinical-trial","evidence-supports","Coadministration of single, oral doses of zaleplon with erythromycin (10 mg and 800 mg, respectively), a strong, selective CYP3A4 inhibitor, produced a 34% increase in zaleplon's maximal plasma concentrations and a 20% increase in the area under the plasma concentration-time curve. ","ncit:positive","ncit:quantitative",,"zaleplon","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","10","erythromycin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","80","SD","Oral","1","SD","Oral","1","UNK","20","Percent","Increase","UNK","UNK","UNK","34","Percent","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:39:55 -0700","drug-drug-interaction","evidence-supports","Concomitant treatment with CLOZARIL and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology (12.3)]. Use caution and monitor patients closely when using such inhibitors. Consider reducing the CLOZARIL dose [see Dosage and Administration (2.6)].","ncit:positive","ncit:Qualitative","escitalopram can increase clozapine levels","escitalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"clozapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:41:56 -0700","drug-drug-interaction","evidence-supports","Concomitant treatment with CLOZARIL and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology (12.3)]. Use caution and monitor patients closely when using such inhibitors. Consider reducing the CLOZARIL dose [see Dosage and Administration (2.6)]","ncit:positive","ncit:Qualitative","Quinidine can increase clozapine levels","quinidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"clozapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:07:13 -0800","DDI-clinical-trial","evidence-challenges","When nefazodone (200 mg BID) and cimetidine (300 mg QID) were coadministered for one week, no change in the steady-state pharmacokinetics of either nefazodone or cimetidine was observed compared to each dosed alone. Therefore, dosage adjustment is not necessary for either drug when coadministered.","ncit:negative","ncit:quantitative",,"nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","200","cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","300","BID","Oral","7","QID","Oral","7","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d78e9639-6fab-4a78-8b29-6991a18ae6c6.html","2016-02-19 17:46:51 -0500","drug-drug-interaction","evidence-supports","In one study of 45 elderly patients suffering from dementia treated with perphenazine, the 5 patients who were prospectively identified as poor P450 2D6 metabolizers had reported significantly greater side effects during the first 10 days of treatment than the 40 extensive metabolizers, following which the groups tended to converge. Prospective phenotyping of elderly patients prior to antipsychotic treatment may identify those at risk for adverse events. The concomitant administration of other drugs that inhibit the activity of P450 2D6 may acutely increase plasma concentrations of antipsychotics. Among these are tricyclic antidepressants and selective serotonin reuptake inhibitors, e.g., fluoxetine, sertraline and paroxetine. When prescribing these drugs to patients already receiving antipsychotic therapy, close monitoring is essential and dose reduction may become necessary to avoid toxicity. Lower doses than usually prescribed for either the antipsychotic or the other drug may be required.","ncit:positive","ncit:Qualitative","may acutely increase plasma concentrations of antipsychotics.","fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"perphenazine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/9c4bedb4-2d59-4fcd-aad7-fce988cd96d8.html","2016-02-29 14:37:32 -0700","DDI-clinical-trial","evidence-supports","The effect of fluvoxamine (25 mg b.i.d. for one week) on thioridazine steady-state concentration was evaluated in ten male inpatients with schizophrenia. Concentrations of thioridazine and its two active metabolites, mesoridazine and sulforidazine, increased 3-fold following coadministration of fluvoxamine. Fluvoxamine and thioridazine should not be coadministered.","ncit:positive","ncit:quantitative",,"mesoridazine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","25","Fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","BID","Oral","7","10","3","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 17:50:18 -0700","DDI-clinical-trial","evidence-challenges","Venlafaxine: Coadministration of a single dose of zaleplon 10 mg and multiple doses of venlafaxine ER (extended release) 150 mg did not result in any significant changes in the pharmacokinetics of either zaleplon or venlafaxine. In addition, there was no pharmacodynamic interaction as a result of coadministration of zaleplon and venlafaxine ER.","ncit:negative","ncit:quantitative","did not result in any significant changes in the pharmacokinetics of either zaleplon or venlafaxine","zaleplon","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","10","venlafaxine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","150","UNK","Oral","UNK","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c6e131fe-e7df-4876-83f7-9156fc4e8228.html","2016-03-14 15:25:58 -0700","DDI-clinical-trial","evidence-supports","Co-administered drug and dosing regimen Atorvastatin Dose (mg) Change in AUC* Change in Cmax* * Data given as x-fold change represent a simple ratio between co-administration and atorvastatin alone (i.e., 1-fold = no change). Data given as % change represent % difference relative to atorvastatin alone (i.e., 0% = no change). † See Sections 5.1 and 7 for clinical significance. ‡ The dose of saquinavir plus ritonavir in this study is not the clinically used dose. The increase in atorvastatin exposure when used clinically is likely to be higher than what was observed in this study. Therefore, caution should be applied and the lowest dose necessary should be used. § Greater increases in AUC (up to 2.5 fold) and/or Cmax (up to 71%) have been reported with excessive grapefruit consumption (≥ 750 mL – 1.2 liters per day). ¶ Single sample taken 8–16 h post dose. # Due to the dual interaction mechanism of rifampin, simultaneous co-administration of atorvastatin with rifampin is recommended, as delayed administration of atorvastatin after administration of rifampin has been associated with a significant reduction in atorvastatin plasma concentrations. †Cyclosporine 5.2 mg/kg/day, stable dose 10 mg QD for 28 days ↑ 8.7 fold ↑ 10.7 fold","ncit:positive","ncit:quantitative","Table 3","atorvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","10","Cyclosporine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","5.2mg/kg/day","QD","Oral","28","Daily","Oral","UNK","UNK","8.7","Fold","Increase","UNK","UNK","UNK","10.7","Fold","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 15:52:59 -0700","DDI-clinical-trial","evidence-supports","When coadministered with a loading dose of 180 mg ticagrelor, the AUCτ,ss and Cmax,ss of dabigatran increased by 49% and 65%, respectively","ncit:positive","ncit:quantitative",,"ticagrelor","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","180","dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","SD","Oral","1","UNK","49","Percent","Increase","UNK","UNK","UNK","65","UNK","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 17:48:17 -0700","DDI-clinical-trial","evidence-challenges","In addition, there were no significant pharmacokinetic interactions observed in studies comparing concomitant rivaroxaban 20 mg and 7.5 mg single dose of midazolam ","ncit:negative","ncit:quantitative","no significant pharmacokinetic interactions observed","midazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","7.5","rivaroxaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","20","UNK","Oral","UNK","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c6e131fe-e7df-4876-83f7-9156fc4e8228.html","2016-03-30 18:03:19 -0400","drug-drug-interaction","evidence-challenges","LIPITOR had no clinically significant effect on prothrombin time when administered to patients receiving chronic warfarin treatment.","ncit:negative","ncit:Qualitative","Concomitant Lipitor and warfarin had no clinically significant effect on prothrombin time","warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","LIPITOR","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2015-11-29 15:19:40 -0700","DDI-clinical-trial","evidence-challenges","luoxetine: A single 3 mg dose of iloperidone had no effect on the pharmacokinetics of fluoxetine (20 mg twice daily). ","ncit:negative","ncit:quantitative",,"fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","20","iloperidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","3","BID","Oral","UNK","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:51:51 -0700","DDI-clinical-trial","evidence-supports","A single-dose interaction study with zolpidem tartrate 5 mg and ketoconazole, a potent CYP3A4 inhibitor, given as 200 mg twice daily for 2 days increased Cmax of zolpidem (30%) and the total AUC of zolpidem (70%) compared to zolpidem alone and prolonged the elimination half-life (30 %) along with an increase in the pharmacodynamic effects of zolpidem. Consideration should be given to using a lower dose of zolpidem when ketoconazole and zolpidem are given together.","ncit:positive","ncit:quantitative",,"ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","zolpidem","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","5","SD","Oral","1","BID","Oral","2","UNK","70","UNK","Increase","UNK","UNK","UNK","30","Percent","Increase","30","Percent","Increase" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 13:12:47 -0800","DDI-clinical-trial","evidence-challenges","Nefazodone plasma concentrations were unaffected by alprazolam. ","ncit:negative","ncit:quantitative",,"Nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","200","alprazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","1","BID","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:39:52 -0700","DDI-clinical-trial","evidence-supports","Ritonavir (combined P-gp and strong CYP3A4 inhibitor): Single-dose rivaroxaban AUC and Cmax increased by 150% and 60%, respectively. Similar increases in pharmacodynamic effects were also observed.","ncit:positive","ncit:quantitative",,"rivaroxaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","Ritonavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","150","Percent","Increase","UNK","UNK","UNK","60","UNK","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/39a5dae2-49f7-4662-9eac-aa7b4c7807a4.html","2016-05-09 16:27:24 -0700","drug-drug-interaction","evidence-supports","CYP3A4 is a major metabolic pathway for elimination of eszopiclone. The exposure of eszopiclone was increased by coadministration of ketoconazole, a potent inhibitor of CYP3A4. ","ncit:positive","ncit:Qualitative","exposure of eszopiclone was increased by coadministration of ketoconazole","eszopiclone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 14:24:30 -0800","DDI-clinical-trial","evidence-challenges"," When fluoxetine (20 mg QD) and nefazodone (200 mg BID) were administered at steady state there were no changes in the pharmacokinetic parameters for fluoxetine or its metabolite, norfluoxetine.","ncit:negative","ncit:quantitative",,"nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","norfluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","20","QD","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 10:40:46 -0800","DDI-clinical-trial","evidence-challenges","Desipramine – When nefazodone (150 mg BID) and desipramine (75 mg QD) were administered together there were no changes in the pharmacokinetics of desipramine or its metabolite, 2-hydroxy desipramine. ","ncit:negative","ncit:quantitative",,"2-hydroxy desipramine.","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","75","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","150","QD","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 16:15:52 -0700","drug-drug-interaction","evidence-supports","Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin. (See CONTRAINDICATIONS, WARNINGS, Myopathy/Rhabdomyolysis, and CLINICAL PHARMACOLOGY, Pharmacokinetics.)","ncit:positive","ncit:Qualitative","Teleprevir is a strong inhibitor of CYP3A4 and reduces the elimination of lovastatin","lovastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","telaprevir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/9c4bedb4-2d59-4fcd-aad7-fce988cd96d8.html","2016-02-29 16:44:38 -0500","drug-drug-interaction","evidence-supports","Concurrent administration of pindolol and thioridazine have resulted in moderate, dose related increases in the serum levels of thioridazine and two of its metabolites, as well as higher than expected serum pindolol levels. Pindolol and thioridazine should not be coadministered.","ncit:positive","ncit:Qualitative","dose related increases in the serum levels of thioridazine and two of its metabolites,","pindolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"thioridazine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a4ee3907-45d4-41b9-af8a-39a9966cd533.html","2016-05-10 13:18:17 -0400","drug-drug-interaction","evidence-challenges","The pharmacokinetic profile of temazepam does not appear to be altered by orally administered cimetidine dosed according to labeling.","ncit:negative","ncit:Qualitative","harmacokinetic profile of temazepam does not appear to be altered by orally administered cimetidine","cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"temazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-12 10:33:55 -0700","DDI-clinical-trial","evidence-challenges"," Enoxaparin 40 mg given subcutaneously for 3 days with the last dose given 24 hours before a single dose of PRADAXA had no impact on the exposure to dabigatran or the coagulation measures aPTT, ECT, or TT","ncit:negative","ncit:quantitative","enoxaparin had no impact on the exposure to dabigatran","dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","Enoxaparin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","SD","Oral","1","UNK","UNK","3","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 14:07:38 -0800","DDI-clinical-trial","evidence-supports","With 5 mg BID doses of buspirone, slight increases in AUC were observed for nefazodone (23%) and its metabolites hydroxynefazodone (17%) and mCPP (9%)","ncit:positive","ncit:quantitative",,"hydroxynefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","250","buspirone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","5","BID","Oral","UNK","BID","Oral","UNK","UNK","17","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 12:46:01 -0700","drug-drug-interaction","evidence-supports"," Omeprazole and rifampin may cause an increase in olanzapine clearance. ","ncit:positive","ncit:Qualitative","may cause an increase in olanzapine clearance.","olanzapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Omeprazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 12:00:53 -0800","DDI-clinical-trial","evidence-supports","HMG-CoA Reductase Inhibitors – When single 40 mg doses of simvastatin or atorvastatin, both substrates of CYP3A4, were given to healthy adult volunteers who had received nefazodone hydrochloride, 200 mg BID for 6 days, approximately 20 fold increases in plasma concentrations of simvastatin and simvastatin acid and 3 to 4 fold increases in plasma concentrations of atorvastatin and atorvastatin lactone were seen. These effects appear to be due to the inhibition of CYP3A4 by nefazodone because, in the same study, nefazodone had no significant effect on the plasma concentrations of pravastatin, which is not metabolized by CYP3A4 to a clinically significant extent.","ncit:positive","ncit:quantitative","entered plasma concentration increase as AUC","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","simvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","40","QD","Oral","1","BID","Oral","6","UNK","20","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 14:35:40 -0800","DDI-clinical-trial","evidence-supports","When fluoxetine (20 mg QD) and nefazodone (200 mg BID) were administered at steady state there were no changes in the pharmacokinetic parameters for fluoxetine or its metabolite, norfluoxetine. Similarly, there were no changes in the pharmacokinetic parameters of nefazodone or HO-NEF; however, the mean AUC levels of the nefazodone metabolites mCPP and triazole-dione increased by 3 to 6 fold and 1.3 fold, respectively","ncit:positive","ncit:quantitative",,"triazole-dione","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","200","fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","BID","Oral","UNK","QD","Oral","UNK","UNK","1.3","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e1e5249-1cb7-4cc2-ad5a-cdeeee2f494f.html","2016-02-16 16:33:50 -0700","drug-drug-interaction","evidence-supports","Quetiapine exposure is increased by the prototype CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.)","ncit:positive","ncit:Qualitative","quetiapine exposure is increased by CYP3A4 inhibitors","Quetiapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:41:53 -0800","DDI-clinical-trial","evidence-supports","Propranolol – The coadministration of nefazodone (200 mg BID) and propranolol (40 mg BID) for 5.5 days to healthy male volunteers (n = 18), including 3 poor and 15 extensive CYP2D6 metabolizers, resulted in 30% and 14% reductions in Cmax and AUC of propranolol, respectively, and a 14% reduction in Cmax for the metabolite, 4-hydroxypropranolol.","ncit:positive","ncit:quantitative",,"4-hydroxypropranolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","40","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","BID","Oral","5.5","BID","Oral","5.5","18","UNK","UNK","UNK","UNK","UNK","UNK","14","Percent","Decrease","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-31 12:59:55 -0700","drug-drug-interaction","evidence-challenges","Data from drug-drug interaction studies involving fluvastatin and coadministration of either gemfibrozil, tolbutamide or losartan indicate that the PK disposition of either gemfibrozil, tolbutamide or losartan is not significantly altered when coadministered with fluvastatin","ncit:negative","ncit:Qualitative","PK disposition of tolbutamide is not significantly altered when coadministered with fluvastatin.","fluvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"tolbutamide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ee49f3b1-1650-47ff-9fb1-ea53fe0b92b6.html","2016-03-14 13:48:36 -0700","DDI-clinical-trial","evidence-supports","The effects of ABILIFY on the exposures of other drugs are summarized in Figure 21. A population PK analysis in patients with major depressive disorder showed no substantial change in plasma concentrations of fluoxetine (20 mg/day or 40 mg/day), paroxetine CR (37.5 mg/day or 50 mg/day), or sertraline (100 mg/day or 150 mg/day) dosed to steady-state. The steady-state plasma concentrations of fluoxetine and norfluoxetine increased by about 18% and 36%, respectively, and concentrations of paroxetine decreased by about 27%. The steady-state plasma concentrations of sertraline and desmethylsertraline were not substantially changed when these antidepressant therapies were coadministered with aripiprazole.","ncit:positive","ncit:quantitative","this was a pop pk study","ABILIFY","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","20-40","Daily","Oral","UNK","UNK","Oral","UNK","UNK","18","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:49:24 -0700","DDI-clinical-trial","evidence-supports","A single-dose interaction study with zolpidem tartrate 10 mg and rifampin 600 mg at steady-state levels in female subjects showed significant reductions of the AUC (-73%), Cmax (-58%), and T1/2 (-36 %) of zolpidem together with significant reductions in the pharmacodynamic effects of zolpidem tartrate. Rifampin, a CYP3A4 inducer, significantly reduced the exposure to and the pharmacodynamic effects of zolpidem.","ncit:positive","ncit:quantitative",,"rifampin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","zolpidem","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","10","SD","Oral","1","UNK","Oral","UNK","UNK","73","Percent","Decrease","UNK","UNK","UNK","58","Percent","Decrease","36","Percent","Increase" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 10:47:19 -0800","DDI-clinical-trial","evidence-supports","There were also no changes in the pharmacokinetics of nefazodone or its triazole-dione metabolite, but the AUC and Cmax of mCPP increased by 44% and 48%, respectively, while the AUC of HO-NEF decreased by 19%. No changes in doses of either nefazodone or desipramine are necessary when the two drugs are given concomitantly. Subsequent dose adjustments should be made on the basis of clinical response.","ncit:positive","ncit:quantitative",,"HO-NEF","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","150","desipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","75","BID","Oral","UNK","QD","Oral","UNK","UNK","19","Percent","Decrease","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/49c4105b-e518-481c-a248-6684135f5bc1.html","2015-11-29 16:36:20 -0700","DDI-clinical-trial","evidence-supports","Repeated oral doses of risperidone (4 mg once daily) did not affect the pre-dose or average plasma concentrations and exposure (AUC) of valproate (1000 mg/day in three divided doses) compared to placebo (n=21). However, there was a 20% increase in valproate peak plasma concentration (Cmax) after concomitant administration of risperidone. Dose adjustment for valproate is not recommended.","ncit:positive","ncit:quantitative",,"risperidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","4","valproate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","1000","Daily","Oral","UNK","QD","Oral","UNK","21","UNK","UNK","UNK","UNK","UNK","UNK","20","Percent","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/fdbfe194-b845-42c5-bb87-a48118bc72e7.html","2016-03-31 12:22:09 -0700","drug-drug-interaction","evidence-supports","Elevated plasma levels of HMG-CoA reductase inhibitory activity increases the risk of myopathy and rhabdomyolysis, particularly with higher doses of simvastatin. [See Warnings and Precautions (5.1) and Clinical Pharmacology (12.3).] Concomitant use of drugs labeled as having a strong inhibitory effect on CYP3A4 is contraindicated [see Contraindications (4)]. If treatment with itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with simvastatin must be suspended during the course of treatment.","ncit:positive","ncit:Qualitative","strong inhibitor of CYP3A4 may elevate simvastatin plasma level","ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"simvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 16:25:17 -0700","DDI-clinical-trial","evidence-challenges","Multiple doses of olanzapine did not influence the kinetics of biperiden. ","ncit:negative","ncit:quantitative",,"olanzapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","biperiden","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/9c4bedb4-2d59-4fcd-aad7-fce988cd96d8.html","2016-02-29 14:34:13 -0700","DDI-clinical-trial","evidence-supports","The effect of fluvoxamine (25 mg b.i.d. for one week) on thioridazine steady-state concentration was evaluated in ten male inpatients with schizophrenia. Concentrations of thioridazine and its two active metabolites, mesoridazine and sulforidazine, increased 3-fold following coadministration of fluvoxamine. Fluvoxamine and thioridazine should not be coadministered.","ncit:positive","ncit:quantitative",,"thioridazine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","Fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","25","UNK","Oral","UNK","BID","Oral","7","10","3","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c6e131fe-e7df-4876-83f7-9156fc4e8228.html","2016-03-14 14:57:35 -0700","DDI-clinical-trial","evidence-supports","Atorvastatin and atorvastatin-metabolites are substrates of the OATP1B1 transporter. Inhibitors of the OATP1B1 (e.g., cyclosporine) can increase the bioavailability of atorvastatin. Atorvastatin AUC was significantly increased with concomitant administration of LIPITOR 10 mg and cyclosporine 5.2 mg/kg/day compared to that of LIPITOR alone [see Clinical Pharmacology (12.3)]. The co-administration of LIPITOR with cyclosporine should be avoided ","ncit:positive","ncit:quantitative","Atorvastatin AUC was significantly increased with concomitant administration of LIPITOR 10 mg and cyclosporine 5.2 mg/kg/day compared to that of LIPITOR alone","atorvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","10","cyclosporine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","5.2 mg/kg/day","UNK","Oral","UNK","Daily","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:26:31 -0700","drug-drug-interaction","evidence-supports","In drug interaction studies evaluating the concomitant use with drugs that are combined P-gp and CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin, erythromycin and fluconazole), increases in rivaroxaban exposure and pharmacodynamic effects (i.e., factor Xa inhibition and PT prolongation) were observed. The increases in exposure ranged from 30% to 160%. Significant increases in rivaroxaban exposure may increase bleeding risk [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative","increases in rivaroxaban exposure","rivaroxaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","clarithromycin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 17:35:54 -0700","drug-drug-interaction","evidence-challenges"," In a single-dose drug interaction study there were no pharmacokinetic or pharmacodynamic interactions observed after concomitant administration of naproxen or aspirin (acetylsalicylic acid) with XARELTO.","ncit:negative","ncit:Qualitative","no pharmacokinetic or pharmacodynamic interactions observed after concomitant administration of naproxen or aspirin (acetylsalicylic acid) with XARELTO.","XARELTO","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","naproxen","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/036db1f2-52b3-42a0-acf9-817b7ba8c724.html","2015-12-08 19:04:34 -0700","DDI-clinical-trial","evidence-challenges","Population pharmacokinetic analysis of schizophrenic patients enrolled in controlled clinical trials has not revealed evidence of any clinically significant pharmacokinetic interactions with benztropine, propranolol, or lorazepam. The absolute bioavailability of a 20 mg dose under fed conditions is approximately 60%. The absorption of ziprasidone is increased up to two-fold in the presence of food","ncit:negative","ncit:quantitative",,"propranolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","ziprasidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a0da0dba-a56d-486b-a45b-e8a7cdfbeac6.html","2016-05-10 10:30:28 -0700","DDI-clinical-trial","evidence-supports","Coadministration of erythromycin increased the maximum plasma concentration of triazolam by 46%, decreased clearance by 53%, and increased half-life by 35%; caution and consideration of appropriate triazolam dose reduction are recommended. Similar caution should be observed during coadministration with clarithromycin and other macrolide antibiotics.","ncit:positive","ncit:quantitative",,"triazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","erythromycin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","53","Percent","Decrease","46","Percent","Increase","35","Percent","Increase" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/39a5dae2-49f7-4662-9eac-aa7b4c7807a4.html","2016-05-09 16:39:00 -0700","DDI-clinical-trial","evidence-supports","Coadministration of eszopiclone 3 mg to subjects receiving ketoconazole, a potent inhibitor of CYP3A4, 400 mg daily for 5 days, resulted in a 2.2-fold increase in exposure to eszopiclone. Cmax and t1/2 were increased 1.4-fold and 1.3-fold, respectively. LUNESTA would not be expected to alter the clearance of drugs metabolized by common CYP450 enzymes [see Warnings and Precautions (5.7), Dosage and Administration (2.3)]. ","ncit:positive","ncit:quantitative",,"eszopiclone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","3","ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","400","UNK","Oral","5","Daily","Oral","5","UNK","2.2","Percent","Increase","UNK","UNK","UNK","1.4","Fold","Increase","1.3","Fold","Increase" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:40:30 -0700","drug-drug-interaction","evidence-supports","Concomitant treatment with CLOZARIL and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology (12.3)]. Use caution and monitor patients closely when using such inhibitors. Consider reducing the CLOZARIL dose [see Dosage and Administration (2.6)","ncit:positive","ncit:Qualitative","paroxetine can increase clozapine levels","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"clozapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 17:32:29 -0700","DDI-clinical-trial","evidence-challenges","Paroxetine: Coadministration of a single dose of Zaleplon 20 mg and paroxetine 20 mg daily for 7 days did not produce any interaction on psychomotor performance. Additionally, paroxetine did not alter the pharmacokinetics of Zaleplon, reflecting the absence of a role of CYP2D6 in zaleplon's metabolism.","ncit:negative","ncit:quantitative","paroxetine did not alter the pharmacokinetics of Zaleplon, reflecting the absence of a role of CYP2D6 in zaleplon's metabolism.","zaleplon","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","20","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","SD","Oral","1","Daily","Oral","7","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 12:14:12 -0800","drug-drug-interaction","evidence-supports","Lithium – In 13 healthy subjects the coadministration of nefazodone (200 mg BID) with lithium (500 mg BID) for 5 days (steady-state conditions) was found to be well tolerated. When the two drugs were coadministered, there were no changes in the steady-state pharmacokinetics of either lithium, nefazodone, or its metabolite HO-NEF; however, there were small decreases in the steady-state plasma concentrations of two nefazodone metabolites, mCPP and triazole-dione, which are considered not to be of clinical significance. Therefore, no dosage adjustment of either lithium or nefazodone is required when they are coadministered.","ncit:positive","ncit:Qualitative","small decreases in the steady-state plasma concentrations","Lithium","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"triazole-dione","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/036db1f2-52b3-42a0-acf9-817b7ba8c724.html","2015-12-08 19:00:54 -0700","DDI-clinical-trial","evidence-challenges","A pharmacokinetic interaction of ziprasidone with valproate is unlikely due to the lack of common metabolic pathways for the two drugs. Ziprasidone dosed adjunctively to valproate in a maintenance trial of bipolar patients did not affect mean therapeutic valproate levels.","ncit:negative","ncit:quantitative",,"ziprasidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","valproate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 11:01:28 -0700","drug-drug-interaction","evidence-challenges","In dedicated studies conducted in healthy subjects, famotidine, atenolol, prasugrel, and enoxaparin did not meaningfully alter the pharmacokinetics of apixaban.","ncit:negative","ncit:Qualitative","atenolol did not meaningfully alter the pharmacokinetics of apixaban","apixaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","atenolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 16:14:20 -0700","drug-drug-interaction","evidence-supports","Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin. (See CONTRAINDICATIONS, WARNINGS, Myopathy/Rhabdomyolysis, and CLINICAL PHARMACOLOGY, Pharmacokinetics.)","ncit:positive","ncit:Qualitative","Telithromycin is a strong inhibitor of CYP3A4 and reduces the elimination of lovastatin","telithromycin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"lovastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 16:05:23 -0700","drug-drug-interaction","evidence-challenges","n clinical studies exploring CYP3A4, CYP2C9, P-gp and other pathways, dabigatran did not meaningfully alter the pharmacokinetics of amiodarone, atorvastatin, clarithromycin, diclofenac, clopidogrel, digoxin, pantoprazole, or ranitidine.","ncit:negative","ncit:Qualitative","dabigatran did not meaningfully alter the pharmacokinetics of atorvastatin","atorvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","dabigatran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 13:21:48 -0700","DDI-clinical-trial","evidence-challenges","Olanzapine (10 mg daily for 2 weeks) did not affect the steady state plasma concentrations of valproate","ncit:negative","ncit:quantitative",,"valproate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","Olanzapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","10","UNK","Oral","UNK","QD","Oral","14","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 18:09:38 -0700","DDI-clinical-trial","evidence-challenges"," There is no pharmacokinetic interaction between zaleplon and diphenhydramine following the administration of a single dose (10 mg and 50 mg, respectively) of each drug. However, because both of these compounds have CNS effects, an additive pharmacodynamic effect is possible.","ncit:negative","ncit:quantitative","no pharmacokinetic interaction between zaleplon and diphenhydramine","zaleplon","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","10","diphenhydramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","50","SD","Oral","1","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 12:44:17 -0700","drug-drug-interaction","evidence-challenges","Warfarin (20 mg single dose) did not affect olanzapine pharmacokinetics ","ncit:negative","ncit:Qualitative","Single dose warfarin did not affect olanzapine pharmacokinetics","olanzapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:42:40 -0700","DDI-clinical-trial","evidence-supports","Clarithromycin (combined P-gp and strong CYP3A4 inhibitor): Single-dose rivaroxaban AUC and Cmax increased by 50% and 40%, respectively. The smaller increases in exposure observed for clarithromycin compared to ketoconazole or ritonavir may be due to the relative difference in P-gp inhibition.","ncit:positive","ncit:quantitative",,"clarithromycin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","rivaroxaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","50","UNK","Increase","UNK","UNK","UNK","40","UNK","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:32:16 -0700","drug-drug-interaction","evidence-supports"," Rifampin Rifampin, a CYP3A4 inducer, significantly reduced the exposure to and the pharmacodynamic effects of zolpidem. Use of Rifampin in combination with zolpidem may decrease the efficacy of zolpidem.","ncit:positive","ncit:Qualitative","significantly reduced the exposure to","Rifampin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"zolpidem","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2015-11-29 14:49:58 -0700","DDI-clinical-trial","evidence-supports","Paroxetine: Co-administration of paroxetine (20 mg/day for 5 to 8 days), a potent inhibitor of CYP2D6, with multiple doses of iloperidone (8 or 12 mg twice daily) to patients with schizophrenia ages 18 to 65 years resulted in increased mean steady-state peak concentrations of iloperidone and its metabolite P88, by about 1.6-fold, and decreased mean steady-state peak concentrations of its metabolite P95 by one-half. Iloperidone doses should be reduced by one-half when administered with paroxetine. ","ncit:positive","ncit:quantitative",,"iloperidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","8 or 12","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","BID","Oral","UNK","Daily","Oral","5 to 8","UNK","UNK","UNK","UNK","UNK","UNK","UNK","1.6","Fold","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e1e5249-1cb7-4cc2-ad5a-cdeeee2f494f.html","2016-02-16 16:45:41 -0700","drug-drug-interaction","evidence-supports","Quetiapine exposure is increased by the prototype CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.)","ncit:positive","ncit:Qualitative","quetiapine exposure is increased by CYP3A4 inhibitors","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"Quetiapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:47:38 -0700","DDI-clinical-trial","evidence-supports","A single-dose interaction study with zolpidem tartrate 10 mg and itraconazole 200 mg at steady-state levels in male volunteers resulted in a 34% increase in AUC0–∞ of zolpidem tartrate. There were no pharmacodynamic effects of zolpidem detected on subjective drowsiness, postural sway, or psychomotor performance.","ncit:positive","ncit:quantitative",,"itraconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","zolpidem","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","10","SD","Oral","1","UNK","Oral","UNK","UNK","34","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a0da0dba-a56d-486b-a45b-e8a7cdfbeac6.html","2016-05-10 13:45:18 -0400","DDI-clinical-trial","evidence-supports","Coadministration of ranitidine increased the maximum plasma concentration of triazolam by 30%, increased the area under the concentration curve by 27%, and increased half-life by 3.3%. Caution is recommended during coadministration with triazolam.","ncit:positive","ncit:quantitative",,"triazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","ranitidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","27","Percent","Increase","UNK","UNK","UNK","30","Percent","Increase","3.3","Percent","Increase" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2015-11-29 14:35:23 -0700","DDI-clinical-trial","evidence-supports","Ketoconazole: Co-administration of ketoconazole (200 mg twice daily for 4 days), a potent inhibitor of CYP3A4, with a 3 mg single dose of iloperidone to 19 healthy volunteers, ages 18 to 45 years, increased the area under the curve (AUC) of iloperidone and its metabolites P88 and P95 by 57%, 55% and 35%, respectively. Iloperidone doses should be reduced by about one-half when administered with ketoconazole or other strong inhibitors of CYP3A4 (e.g., itraconazole). Weaker inhibitors (e.g., erythromycin, grapefruit juice) have not been studied. When the CYP3A4 inhibitor is withdrawn from the combination therapy, the iloperidone dose should be returned to the previous level.","ncit:positive","ncit:quantitative",,"ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","P88","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","3","SD","Oral","1","BID","Oral","4","19","55","Percent","Increase","UNKUNUNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/44dcbf97-99ec-427c-ba50-207e0069d6d2.html","2016-03-31 10:15:25 -0700","drug-drug-interaction","evidence-supports","Rifampin significantly increased pitavastatin exposure. In patients taking rifampin, a dose of LIVALO 2 mg once daily should not be exceeded [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative","Rifampin significantly increased pitavastatin exposure. Study details in section 12 Table 3","Rifampin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"pitavastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 17:53:05 -0700","DDI-clinical-trial","evidence-challenges","n addition, there were no significant pharmacokinetic interactions observed in studies comparing concomitant rivaroxaban 20 mg and 7.5 mg single dose of midazolam (substrate of CYP3A4), 0.375 mg once-daily dose of digoxin (substrate of P-gp), ","ncit:negative","ncit:quantitative","no significant pharmacokinetic interactions observed","digoxin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",".375","rivaroxaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","20","UNK","Oral","UNK","QD","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/9c4bedb4-2d59-4fcd-aad7-fce988cd96d8.html","2016-02-29 14:20:16 -0700","drug-drug-interaction","evidence-supports","Reduced cytochrome P450 2D6 isozyme activity drugs that inhibit this isozyme (e.g., fluoxetine and paroxetine) and certain other drugs (e.g., fluvoxamine, propranolol, and pindolol) appear to appreciably inhibit the metabolism of thioridazine. The resulting elevated levels of thioridazine would be expected to augment the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as Torsades de pointes type arrhythmias.","ncit:positive","ncit:Qualitative","appears to appreciably inhibit the metabolism of thioridazine and result in elevated levels of thioridazine","thioridazine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 10:50:15 -0800","DDI-clinical-trial","evidence-challenges","Lithium – In 13 healthy subjects the coadministration of nefazodone (200 mg BID) with lithium (500 mg BID) for 5 days (steady-state conditions) was found to be well tolerated. When the two drugs were coadministered, there were no changes in the steady-state pharmacokinetics of either lithium, nefazodone, or its metabolite HO-NEF; however, there were small decreases in the steady-state plasma concentrations of two nefazodone metabolites, mCPP and triazole-dione, which are considered not to be of clinical significance. Therefore, no dosage adjustment of either lithium or nefazodone is required when they are coadministered.","ncit:negative","ncit:quantitative",,"nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","Lithium","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","500","BID","Oral","5","BID","Oral","5","13","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2015-12-17 18:44:54 -0700","DDI-clinical-trial","evidence-supports","Midazolam (a sensitive CYP 3A4 substrate): A study in patients with schizophrenia showed a less than 50% increase in midazolam total exposure at iloperidone steady state (14 days of oral dosing at up to 10 mg iloperidone twice daily) and no effect on midazolam Cmax. Thus, an interaction between iloperidone and other CYP3A4 substrates is unlikely.","ncit:positive","ncit:quantitative","less than 50% increase in midazolam total exposure","iloperidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","up to 10","midazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","BID","Oral","14","UNK","UNK","UNK","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e1e5249-1cb7-4cc2-ad5a-cdeeee2f494f.html","2016-02-16 16:45:41 -0700","drug-drug-interaction","evidence-supports","Quetiapine exposure is increased by the prototype CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.)","ncit:positive","ncit:Qualitative","quetiapine exposure is increased by CYP3A4 inhibitors","Quetiapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","ritonavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-30 15:06:21 -0700","drug-drug-interaction","evidence-supports","Cyclosporine coadministration increases fluvastatin exposure. Therefore, in patients taking cyclosporine, therapy should be limited to fluvastatin 20 mg twice daily [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative","Concomitant cyclosporin increases fluvastatin exposure. Details in Section 12 Table 3","Cyclosporine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"fluvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e1e5249-1cb7-4cc2-ad5a-cdeeee2f494f.html","2016-02-16 16:45:41 -0700","drug-drug-interaction","evidence-supports","Quetiapine exposure is increased by the prototype CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.). and decreased by the prototype CYP3A4 inducers (e..g, phenytoin, carbamazepine, rifampin, avasimibe, St. John’s wort etc.).","ncit:positive","ncit:Qualitative","quetiapine exposure is decreased by CYP3A4 inducers","rifampin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"Quetiapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c6e131fe-e7df-4876-83f7-9156fc4e8228.html","2016-03-14 14:59:55 -0700","drug-drug-interaction","evidence-supports","Concomitant administration of LIPITOR with inducers of cytochrome P450 3A4 (e.g., efavirenz, rifampin) can lead to variable reductions in plasma concentrations of atorvastatin. Due to the dual interaction mechanism of rifampin, simultaneous co-administration of LIPITOR with rifampin is recommended, as delayed administration of LIPITOR after administration of rifampin has been associated with a significant reduction in atorvastatin plasma concentrations. ","ncit:positive","ncit:Qualitative","administration of rifampin has been associated with a significant reduction in atorvastatin plasma concentrations.\n\tadministration of rifampin has been associated with a significant reduction in atorvastatin plasma concentrations.\n\tadministration of rifampin has been associated with a significant reduction in atorvastatin plasma concentrations.","rifampin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"atorvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-31 16:00:41 -0400","drug-drug-interaction","evidence-challenges","Data from drug-drug interaction studies involving fluvastatin and coadministration of either gemfibrozil, tolbutamide or losartan indicate that the PK disposition of either gemfibrozil, tolbutamide or losartan is not significantly altered when coadministered with fluvastatin","ncit:negative","ncit:Qualitative","PK disposition of losartan is not significantly altered when coadministered with fluvastatin.","losartan","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1fd0ba23-962e-427f-8b9d-2cf8f64d0f95.html","2016-03-31 14:25:54 -0400","drug-drug-interaction","evidence-challenges","When CRESTOR was coadministered with fenofibrate, no clinically significant increase in the AUC of rosuvastatin or fenofibrate was observed. Because it is known that the risk of myopathy during treatment with HMG-CoA reductase inhibitors is increased with concomitant use of fenofibrates, caution should be used when prescribing fenofibrates with CRESTOR [seeWarnings and Precautions (5.1) andClinical Pharmacology (12.3)].","ncit:negative","ncit:Qualitative","When CRESTOR was coadministered with fenofibrate, no clinically significant increase in the AUC of rosuvastatin or fenofibrate was observed. Study details in Section 12 Table 4","rosuvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fenofibrate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-31 12:59:13 -0700","drug-drug-interaction","evidence-challenges","Data from drug-drug interaction studies involving fluvastatin and coadministration of either gemfibrozil, tolbutamide or losartan indicate that the PK disposition of either gemfibrozil, tolbutamide or losartan is not significantly altered when coadministered with fluvastatin.","ncit:negative","ncit:Qualitative","PK disposition of gemfibrozil is not significantly altered when coadministered with fluvastatin.","gemfibrozil","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2015-11-29 14:46:00 -0700","DDI-clinical-trial","evidence-supports","Fluoxetine: Co-administration of fluoxetine (20 mg twice daily for 21 days), a potent inhibitor of CYP2D6, with a single 3 mg dose of iloperidone to 23 healthy volunteers, ages 29 to 44 years, who were classified as CYP2D6 extensive metabolizers, increased the AUC of iloperidone and its metabolite P88, by about 2- to 3-fold, and decreased the AUC of its metabolite P95 by one-half. Iloperidone doses should be reduced by one-half when administered with fluoxetine. ","ncit:positive","ncit:quantitative",,"fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","P95","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","3","SD","Oral","1","BID","Oral","21","23","50","Percent","Decrease","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 18:12:14 -0700","DDI-clinical-trial","evidence-supports","Concomitant administration of Zaleplon (10 mg) and cimetidine (800 mg) produced an 85% increase in the mean Cmax and AUC of zaleplon. An initial dose of 5 mg should be given to patients who are concomitantly being treated with cimetidine (see DOSAGE AND ADMINISTRATION).","ncit:positive","ncit:quantitative",,"zaleplon","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","10","cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","800","UNK","UNK","UNK","UNK","Oral","UNK","UNK","85","Percent","Increase","UNK","UNK","UNK","85","Percent","Increase","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ee49f3b1-1650-47ff-9fb1-ea53fe0b92b6.html","2016-03-14 17:06:08 -0400","DDI-clinical-trial","evidence-challenges","The effects of ABILIFY on the exposures of other drugs are summarized in Figure 21. A population PK analysis in patients with major depressive disorder showed no substantial change in plasma concentrations of fluoxetine (20 mg/day or 40 mg/day), paroxetine CR (37.5 mg/day or 50 mg/day), or sertraline (100 mg/day or 150 mg/day) dosed to steady-state. The steady-state plasma concentrations of fluoxetine and norfluoxetine increased by about 18% and 36%, respectively, and concentrations of paroxetine decreased by about 27%. The steady-state plasma concentrations of sertraline and desmethylsertraline were not substantially changed when these antidepressant therapies were coadministered with aripiprazole.","ncit:negative","ncit:quantitative","The steady-state plasma concentrations of sertraline and desmethylsertraline were not substantially changed when these antidepressant therapies were coadministered with aripiprazole.","desmethylsertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","100-150","ABILIFY","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","Daily","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:47:05 -0800","DDI-clinical-trial","evidence-challenges","Propranolol – The coadministration of nefazodone (200 mg BID) and propranolol (40 mg BID) for 5.5 days to healthy male volunteers (n = 18), including 3 poor and 15 extensive CYP2D6 metabolizers, resulted in 30% and 14% reductions in Cmax and AUC of propranolol, respectively, and a 14% reduction in Cmax for the metabolite, 4-hydroxypropranolol. The kinetics of nefazodone, hydroxynefazodone, and triazole-dione were not affected by coadministration of propranolol. However, Cmax, Cmin, and AUC of m-chlorophenylpiperazine were increased by 23%, 54%, and 28%, respectively. No change in initial dose of either drug is necessary and dose adjustments should be made on the basis of clinical response.","ncit:negative","ncit:quantitative",,"triazole-dione","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","200","propranolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","BID","Oral","5.5","BID","Oral","5.5","18","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 13:14:56 -0700","DDI-clinical-trial","evidence-challenges","Administration of intramuscular lorazepam (2 mg) 1 hour after intramuscular olanzapine for injection (5 mg) did not significantly affect the pharmacokinetics of olanzapine, unconjugated lorazepam, or total lorazepam.","ncit:negative","ncit:quantitative","Formulation entered as IV but actually IM","lorazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","2","olanzapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","5","SD","IV","1","SD","IV","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2015-11-29 14:38:11 -0700","DDI-clinical-trial","evidence-supports","Ketoconazole: Co-administration of ketoconazole (200 mg twice daily for 4 days), a potent inhibitor of CYP3A4, with a 3 mg single dose of iloperidone to 19 healthy volunteers, ages 18 to 45 years, increased the area under the curve (AUC) of iloperidone and its metabolites P88 and P95 by 57%, 55% and 35%, respectively. Iloperidone doses should be reduced by about one-half when administered with ketoconazole or other strong inhibitors of CYP3A4 (e.g., itraconazole). Weaker inhibitors (e.g., erythromycin, grapefruit juice) have not been studied. When the CYP3A4 inhibitor is withdrawn from the combination therapy, the iloperidone dose should be returned to the previous level.","ncit:positive","ncit:quantitative",,"P95","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","3","ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","SD","Oral","1","BID","Oral","4","19","35","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 11:02:59 -0700","drug-drug-interaction","evidence-challenges","In studies conducted in healthy subjects, apixaban did not meaningfully alter the pharmacokinetics of digoxin, naproxen, atenolol, prasugrel, or acetylsalicylic acid.","ncit:negative","ncit:Qualitative","pixaban did not meaningfully alter the pharmacokinetics of digoxin","digoxin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","apixaban","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"source","date","assertionType","evidenceType","prefix","exactText","suffix","modality","statementType","comment","drug1Lab","drug1Type","drug1Role","dose1","drug2Lab","drug2Type","drug2Role","dose2","objectRegimens","objectFormulation","objectDuration","preciptRegimens","preciptFormulation","preciptDuration","numOfParticipants","auc","aucType","aucDirection","cl","clType","clDirection","cmax","cmaxType","cmaxDirection","t12","t12Type","t12Direction" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 17:58:31 -0700","DDI-clinical-trial","evidence-supports",". In addition, there was no pharmacodynamic interaction as a result of coadministration of zaleplon and venlafaxine ER. ","Promethazine: Coadministration of a single dose of zaleplon and promethazine (10 and 25 mg, respectively) resulted in a 15% decrease in maximal plasma concentrations of zaleplon, but no change in the area under the plasma concentration-time curve. However, the pharmacodynamics of coadministration of zaleplon and promethazine have not been evaluated. Caution should be exercised when these 2 agents are coadministered.","","ncit:positive","ncit:quantitative","but no change in the area under the plasma concentration-time curve.","promethazine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","25","zaleplon","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","10","SD","Oral","1","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","15","Percent","Decrease","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1a5a93be-7bc3-4714-9308-2fbfb8260e23.html","2016-02-29 15:03:48 -0700","drug-drug-interaction","evidence-supports","Phenothiazines can produce alpha-adrenergic blockade. ","Concomitant administration of propranolol with phenothiazines results in increased plasma levels of both drugs.","","ncit:positive","ncit:Qualitative","Concomitant administration of propranolol with phenothiazines results in increased plasma levels of both drugs","propranolol","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"phenothiazines","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 14:55:51 -0700","drug-drug-interaction","evidence-supports","5.5 Effect of P-gp Inducers and Inhibitors on Dabigatran Exposure ","The concomitant use of PRADAXA with P-gp inducers (e.g., rifampin) reduces exposure to dabigatran and should generally be avoided [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative","rifampin reduces exposure to dabigatran","dabigatran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","rifampin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 22:55:21 -0400","drug-drug-interaction","evidence-challenges","combinations revealed no effect of either drug on the pharmacokinetics or pharmacodynamics of zolpidem . ","Zolpidem tartrate had no effect on digoxin pharmacokinetics and did not affect prothrombin time when given with warfarin in healthy subjects.","","ncit:negative","ncit:Qualitative","did not affect prothrombin time when given with warfarin","Zolpidem","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"warfarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 10:48:58 -0700","drug-drug-interaction","evidence-supports","7.2 Strong Dual Inducers of CYP3A4 and P-gp ","Avoid concomitant use of ELIQUIS with strong dual inducers of CYP3A4 and P-gp (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort) because such drugs will decrease exposure to apixaban [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative","rifampin will decrease exposure to apixaban","rifampin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"apixaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ee49f3b1-1650-47ff-9fb1-ea53fe0b92b6.html","2016-03-14 14:01:17 -0700","DDI-clinical-trial","evidence-supports","aripiprazole pharmacokinetics ","The effects of ABILIFY on the exposures of other drugs are summarized in Figure 21. A population PK analysis in patients with major depressive disorder showed no substantial change in plasma concentrations of fluoxetine (20 mg/day or 40 mg/day), paroxetine CR (37.5 mg/day or 50 mg/day), or sertraline (100 mg/day or 150 mg/day) dosed to steady-state. The steady-state plasma concentrations of fluoxetine and norfluoxetine increased by about 18% and 36%, respectively, and concentrations of paroxetine decreased by about 27%. The steady-state plasma concentrations of sertraline and desmethylsertraline were not substantially changed when these antidepressant therapies were coadministered with aripiprazole.","","ncit:positive","ncit:quantitative","this was a pop pk study","ABILIFY","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","norfluoxetine","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","20-40","Daily","Oral","UNK","UNK","UNK","UNK","UNK","36","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 15:06:41 -0700","DDI-clinical-trial","evidence-supports","is administered 2 hours after dabigatran etexilate . ","Ketoconazole: Systemic ketoconazole increased dabigatran AUC and Cmax values by 138% and 135%, respectively, after a single dose of 400 mg, and 153%, and 149%, respectively, after multiple daily doses of 400 mg.","","ncit:positive","ncit:quantitative",,"ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","400","dabigatran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","SD","Oral","1","UNK","138","Percent","Increase","UNK","UNK","UNK","135","Percent","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:26:31 -0700","drug-drug-interaction","evidence-supports","7.1 Drugs that Inhibit Cytochrome P450 3A4 Enzymes and Drug Transport Systems ","In drug interaction studies evaluating the concomitant use with drugs that are combined P-gp and CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin, erythromycin and fluconazole), increases in rivaroxaban exposure and pharmacodynamic effects (i.e., factor Xa inhibition and PT prolongation) were observed. The increases in exposure ranged from 30% to 160%. Significant increases in rivaroxaban exposure may increase bleeding risk [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative","increases in rivaroxaban exposure","rivaroxaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","ritonavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 13:01:39 -0800","DDI-clinical-trial","evidence-supports","","When a single oral 0.25 mg dose of triazolam was coadministered with nefazodone (200 mg BID) at steady state, triazolam half-life and AUC increased 4 fold and peak concentrations increased 1.7 fold. ","Nefazodone","ncit:positive","ncit:quantitative",,"nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","triazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction",".25","SD","Oral","1","BID","Oral","UNK","UNK","4","Fold","Increase","UNK","UNK","UNK","1.7","Fold","Increase","4","Fold","Increase" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/39a5dae2-49f7-4662-9eac-aa7b4c7807a4.html","2016-05-09 19:41:26 -0400","DDI-clinical-trial","evidence-challenges","measured at steady state following dosing of 0.5 mg twice daily for one day and 0.25 mg daily for the next 6 days. ","Warfarin: Eszopiclone 3 mg administered daily for 5 days did not affect the pharmacokinetics of (R)- or (S)-warfarin, nor were there any changes in the pharmacodynamic profile (prothrombin time) following a single 25 mg oral dose of warfarin. ","","ncit:negative","ncit:quantitative","Eszopiclone 3 mg administered daily for 5 days did not affect the pharmacokinetics of warfarin","Eszopiclone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","3","warfarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","25","SD","Oral","1","Daily","Oral","5","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 16:13:29 -0700","drug-drug-interaction","evidence-supports","is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. ","Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin. (See CONTRAINDICATIONS, WARNINGS, Myopathy/Rhabdomyolysis, and CLINICAL PHARMACOLOGY, Pharmacokinetics.)","","ncit:positive","ncit:Qualitative","Clarithromycin is a strong inhibitor of CYP3A4 and reduces the elimination of lovastatin","clarithromycin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"lovastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-30 15:09:14 -0700","drug-drug-interaction","evidence-supports"," 7.7 Phenytoin ","Concomitant administration of fluvastatin and phenytoin increased phenytoin exposures. Patients should continue to be monitored appropriately when fluvastatin therapy is initiated or when fluvastatin dose is changed [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative","Concomitant fluvastatin increases phenytoin exposure. Details in Section 12 Table 3","phenytoin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluvastatin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2015-11-29 14:35:23 -0700","DDI-clinical-trial","evidence-supports","elimination and cause increased blood levels. ","Ketoconazole: Co-administration of ketoconazole (200 mg twice daily for 4 days), a potent inhibitor of CYP3A4, with a 3 mg single dose of iloperidone to 19 healthy volunteers, ages 18 to 45 years, increased the area under the curve (AUC) of iloperidone and its metabolites P88 and P95 by 57%, 55% and 35%, respectively. Iloperidone doses should be reduced by about one-half when administered with ketoconazole or other strong inhibitors of CYP3A4 (e.g., itraconazole). Weaker inhibitors (e.g., erythromycin, grapefruit juice) have not been studied. When the CYP3A4 inhibitor is withdrawn from the combination therapy, the iloperidone dose should be returned to the previous level.","","ncit:positive","ncit:quantitative",,"ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","iloperidone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","3","SD","Oral","1","BID","Oral","4","19","57","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d78e9639-6fab-4a78-8b29-6991a18ae6c6.html","2016-02-19 17:46:51 -0500","drug-drug-interaction","evidence-supports","hydroxylase). Approximately 10% of the Caucasian population has reduced activity of this enzyme, so-called “poor” metabolizers. Among other populations the prevalence is not known. Poor metabolizers demonstrate higher plasma concentrations of antipsychotic drugs at usual doses, which may correlate with emergence of side effects. ","In one study of 45 elderly patients suffering from dementia treated with perphenazine, the 5 patients who were prospectively identified as poor P450 2D6 metabolizers had reported significantly greater side effects during the first 10 days of treatment than the 40 extensive metabolizers, following which the groups tended to converge. Prospective phenotyping of elderly patients prior to antipsychotic treatment may identify those at risk for adverse events. The concomitant administration of other drugs that inhibit the activity of P450 2D6 may acutely increase plasma concentrations of antipsychotics. Among these are tricyclic antidepressants and selective serotonin reuptake inhibitors, e.g., fluoxetine, sertraline and paroxetine. When prescribing these drugs to patients already receiving antipsychotic therapy, close monitoring is essential and dose reduction may become necessary to avoid toxicity. Lower doses than usually prescribed for either the antipsychotic or the other drug may be required.","","ncit:positive","ncit:Qualitative","may acutely increase plasma concentrations of antipsychotics.","paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"perphenazine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-31 12:56:52 -0700","drug-drug-interaction","evidence-challenges","Pharmacokinetic data in the pediatric population are not available. Drug-Drug Interactions: ","Data from drug-drug interactions studies involving coadministration of gemfibrozil, niacin, itraconazole, erythromycin, tolbutamide or clopidogrel indicate that the PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with any of these drugs.","","ncit:negative","ncit:Qualitative","PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with tolbutamide","tolbutamide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"fluvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/9c4bedb4-2d59-4fcd-aad7-fce988cd96d8.html","2016-02-29 14:37:32 -0700","DDI-clinical-trial","evidence-supports"," Fluvoxamine ","The effect of fluvoxamine (25 mg b.i.d. for one week) on thioridazine steady-state concentration was evaluated in ten male inpatients with schizophrenia. Concentrations of thioridazine and its two active metabolites, mesoridazine and sulforidazine, increased 3-fold following coadministration of fluvoxamine. Fluvoxamine and thioridazine should not be coadministered.","","ncit:positive","ncit:quantitative",,"sulforidazine","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","UNK","Fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","25","UNK","Oral","UNK","BID","Oral","7","10","3","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2015-11-29 15:12:19 -0700","DDI-clinical-trial","evidence-supports","does not have enzyme inducing properties, specifically for the following cytochrome P450 isozymes: CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP3A4 and CYP3A5. ","Dextromethorphan: A study in healthy volunteers showed that changes in the pharmacokinetics of dextromethorphan (80 mg dose) when a 3 mg dose of iloperidone was co-administered resulted in a 17% increase in total exposure and a 26% increase in the maximum plasma concentrations (Cmax)of dextromethorphan. Thus, an interaction between iloperidone and other CYP2D6 substrates is unlikely.","","ncit:positive","ncit:quantitative",,"dextromethorphan","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","80","iloperidone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","3","SD","Oral","1","SD","Oral","1","UNK","17","Percent","Increase","UNK","UNK","UNK","26","Percent","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 10:37:19 -0800","DDI-clinical-trial","evidence-challenges","","Phenytoin – Pretreatment for 7 days with 200 mg BID of nefazodone had no effect on the pharmacokinetics of a single 300 mg oral dose of phenytoin. However, due to the nonlinear pharmacokinetics of phenytoin, the failure to observe a significant effect on the single-dose pharmacokinetics of phenytoin does not preclude the possibility of a clinically significant interaction with nefazodone when phenytoin is dosed chronically. ","However, no change in the initial dosage of","ncit:negative","ncit:quantitative",,"nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","Phenytoin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","300","SD","Oral","1","BID","Oral","7","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-02-18 16:49:30 -0700","DDI-clinical-trial","evidence-supports","Drug-Drug Interaction Studies Fluvoxamine ","A pharmacokinetic study was conducted in 16 schizophrenic patients who received clozapine under steady-state conditions. After coadministration of fluvoxamine for 14 days, mean trough concentrations of clozapine and its metabolites, N-desmethylclozapine and clozapine N-oxide, were elevated about 3-fold compared to baseline steady-state concentrations.","","ncit:positive","ncit:quantitative",,"clozapine N-oxide","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","UNK","fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","14","16","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/827cf470-485d-4925-85f2-8933a6dea830.html","2016-03-14 17:27:36 -0400","drug-drug-interaction","evidence-supports"," Drug Interactions ","Hepatic microsomal enzyme inducing agents, such as carbamazepine, were found to significantly increase the clearance of thiothixene. Patients receiving these drugs should be observed for signs of reduced thiothixene effectiveness4,5.","","ncit:positive","ncit:Qualitative","carbemazepine found to significantly increase the clearance of thiothixene","carbamazepine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"thiothixene","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 13:29:38 -0800","DDI-clinical-trial","evidence-challenges","may be necessary when coadministered with nefazodone . ","Lorazepam – When lorazepam (2 mg BID) and nefazodone (200 mg BID) were coadministered to steady state, there was no change in any pharmacokinetic parameter for either drug compared to each drug administered alone. Therefore, dosage adjustment is not necessary for either drug when coadministered.","","ncit:negative","ncit:quantitative",,"Lorazepam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","5","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","SD","Oral","1","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e1e5249-1cb7-4cc2-ad5a-cdeeee2f494f.html","2016-02-16 16:34:55 -0700","drug-drug-interaction","evidence-supports","potentiated the cognitive and motor effects of alcohol in a clinical trial in subjects with selected psychotic disorders, and alcoholic beverages should be limited while taking quetiapine . ","Quetiapine exposure is increased by the prototype CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.)","","ncit:positive","ncit:Qualitative","quetiapine exposure is increased by CYP3A4 inhibitors","indinavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"Quetiapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-31 12:56:20 -0700","drug-drug-interaction","evidence-challenges","Pharmacokinetic data in the pediatric population are not available. Drug-Drug Interactions: ","Data from drug-drug interactions studies involving coadministration of gemfibrozil, niacin, itraconazole, erythromycin, tolbutamide or clopidogrel indicate that the PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with any of these drugs.","","ncit:negative","ncit:Qualitative","PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with erythromycin","erythromycin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"fluvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4b0700c9-b417-4c3a-b36f-de461e125bd3.html","2015-11-29 13:52:49 -0700","DDI-clinical-trial","evidence-challenges","","Coadministration of aspirin 150 mg/day with multiple daily doses of BRINTELLIX had no significant inhibitory effect on platelet aggregation or pharmacokinetics of aspirin and salicylic acid [see Drug Interactions (7.4)].","","ncit:negative","ncit:quantitative",,"salicylic acid","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","150","BRINTELLIX","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","Daily","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNKUNUNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 16:16:27 -0700","drug-drug-interaction","evidence-supports","is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. ","Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin. (See CONTRAINDICATIONS, WARNINGS, Myopathy/Rhabdomyolysis, and CLINICAL PHARMACOLOGY, Pharmacokinetics.)","","ncit:positive","ncit:Qualitative","Nefazodone is a strong inhibitor of CYP3A4 and reduces the elimination of lovastatin","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"lovastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 16:06:57 -0700","drug-drug-interaction","evidence-challenges","Impact of Dabigatran on Other Drugs ","In clinical studies exploring CYP3A4, CYP2C9, P-gp and other pathways, dabigatran did not meaningfully alter the pharmacokinetics of amiodarone, atorvastatin, clarithromycin, diclofenac, clopidogrel, digoxin, pantoprazole, or ranitidine.","","ncit:negative","ncit:Qualitative","dabigatran did not meaningfully alter the pharmacokinetics of clopidogrel","dabigatran","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"clopidogrel","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-31 12:55:51 -0700","drug-drug-interaction","evidence-challenges","Pharmacokinetic data in the pediatric population are not available. Drug-Drug Interactions: ","Data from drug-drug interactions studies involving coadministration of gemfibrozil, niacin, itraconazole, erythromycin, tolbutamide or clopidogrel indicate that the PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with any of these drugs.","","ncit:negative","ncit:Qualitative","PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with itraconazole","itraconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"fluvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 18:14:59 -0700","DDI-clinical-trial","evidence-challenges","Drugs with a Narrow Therapeutic Index ","Digoxin: Zaleplon (10 mg) did not affect the pharmacokinetic or pharmacodynamic profile of digoxin (0.375 mg q24h for 8 days).","","ncit:negative","ncit:quantitative","Zaleplon did not affect the pharmacokinetic s of digoxin","Zaleplon","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","10","digoxin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction",".375","QD","Oral","8","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/afad3051-9df2-4c54-9684-e8262a133af8.html","2015-12-08 19:35:35 -0700","DDI-clinical-trial","evidence-challenges","","Valproate: It is not necessary to adjust the LATUDA dose when used concomitantly with valproate. A dedicated drug-drug interaction study has not been conducted with valproate and LATUDA. Based on pharmacokinetic data from the bipolar depression studies valproate levels were not affected by lurasidone, and lurasidone concentrations were not affected by valproate. ","","ncit:negative","ncit:quantitative",,"lurasidone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","valproate","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 16:02:33 -0700","drug-drug-interaction","evidence-challenges","digoxin plasma concentrations . ","Oral Hypoglycemic Agents: In pharmacokinetic studies of MEVACOR in hypercholesterolemic non-insulin dependent diabetic patients, there was no drug interaction with glipizide or with chlorpropamide (see CLINICAL PHARMACOLOGY, Clinical Studies).","","ncit:negative","ncit:Qualitative","There was no drug interaction with concomitant lovastatin and chlorpropamide (see CLINICAL PHARMACOLOGY, Clinical Studies)","MEVACOR","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"chlorpropamide","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 13:11:00 -0800","DDI-clinical-trial","evidence-supports"," Alprazolam ","When alprazolam (1 mg BID) and nefazodone (200 mg BID) were coadministered, steady-state peak concentrations, AUC and half-life values for alprazolam increased by approximately 2 fold.","","ncit:positive","ncit:quantitative",,"nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","alprazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","1","BID","Oral","UNK","BID","Oral","UNK","UNK","2","Fold","Increase","UNK","UNK","UNK","2","Fold","Increase","2","Fold","Increase" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1a5a93be-7bc3-4714-9308-2fbfb8260e23.html","2016-02-29 17:07:32 -0500","drug-drug-interaction","evidence-supports","Phenothiazines can produce alpha-adrenergic blockade. ","Concomitant administration of propranolol with phenothiazines results in increased plasma levels of both drugs.","","ncit:positive","ncit:Qualitative","Concomitant administration of propranolol with phenothiazines results in increased plasma levels of both drugs","phenothiazines","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"propranolol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 16:00:52 -0700","drug-drug-interaction","evidence-challenges","digoxin plasma concentrations . ","Oral Hypoglycemic Agents: In pharmacokinetic studies of MEVACOR in hypercholesterolemic non-insulin dependent diabetic patients, there was no drug interaction with glipizide or with chlorpropamide (see CLINICAL PHARMACOLOGY, Clinical Studies).","","ncit:negative","ncit:Qualitative","There was no drug interaction with concomitant lovastatin and glipizide or with chlorpropamide (see CLINICAL PHARMACOLOGY, Clinical Studies).","MEVACOR","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"glipizide","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/9c4bedb4-2d59-4fcd-aad7-fce988cd96d8.html","2016-02-29 14:19:31 -0700","drug-drug-interaction","evidence-supports","","Reduced cytochrome P450 2D6 isozyme activity drugs that inhibit this isozyme (e.g., fluoxetine and paroxetine) and certain other drugs (e.g., fluvoxamine, propranolol, and pindolol) appear to appreciably inhibit the metabolism of thioridazine. The resulting elevated levels of thioridazine would be expected to augment the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as Torsades de pointes type arrhythmias."," Such an increased risk may result also from the additive effect of coadministering","ncit:positive","ncit:Qualitative","appear to appreciably inhibit the metabolism of thioridazine and result in elevated levels of thioridazine","thioridazine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/7d1a9689-23c8-44ef-a474-8c607e13d794.html","2016-03-14 15:46:58 -0400","drug-drug-interaction","evidence-supports",", plasma haloperidol levels were decreased by a mean of 70% and mean scores on the Brief Psychiatric Rating Scale were increased from baseline. ","In 5 other schizophrenic patients treated with haloperidol and rifampin, discontinuation of rifampin produced a mean 3.3-fold increase in haloperidol concentrations. Thus, careful monitoring of clinical status is warranted when rifampin is administered or discontinued in haloperidol-treated patients.","","ncit:positive","ncit:Qualitative","iscontinuation of rifampin produced a mean 3.3-fold increase in haloperidol concentrations.","haloperidol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","rifampin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 14:04:35 -0800","DDI-clinical-trial","evidence-supports","metabolite 1-pyrimidinylpiperazine. ","With 5 mg BID doses of buspirone, slight increases in AUC were observed for nefazodone (23%) and its metabolites hydroxynefazodone (17%) and mCPP (9%).","","ncit:positive","ncit:quantitative",,"buspirone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","5","hydroxynefazodone","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","250","BID","Oral","UNK","BID","Oral","UNK","UNK","17","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 16:06:27 -0700","drug-drug-interaction","evidence-challenges","Impact of Dabigatran on Other Drugs ","In clinical studies exploring CYP3A4, CYP2C9, P-gp and other pathways, dabigatran did not meaningfully alter the pharmacokinetics of amiodarone, atorvastatin, clarithromycin, diclofenac, clopidogrel, digoxin, pantoprazole, or ranitidine.","","ncit:negative","ncit:Qualitative","dabigatran did not meaningfully alter the diclofenac","diclofenac","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","dabigatran","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:37:29 -0700","drug-drug-interaction","evidence-supports","concomitantly with drugs that are inducers or inhibitors of these enzymes. CYP1A2 Inhibitors ","Concomitant use of CLOZARIL and CYP1A2 inhibitors can increase plasma levels of clozapine, potentially resulting in adverse reactions. Reduce the CLOZARIL dose to one-third of the original dose when CLOZARIL is coadministered with strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin, or enoxacin). The CLOZARIL dose should be increased to the original dose when coadministration of strong CYP1A2 inhibitors is discontinued [see Dosage and Administration (2.6), Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative","ciprofloxacin can increase clozapine levels","clozapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","ciprofloxacin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 13:28:51 -0700","DDI-clinical-trial","evidence-challenges"," — ","Single doses of olanzapine did not affect the pharmacokinetics of imipramine or its active metabolite desipramine.","","ncit:negative","ncit:quantitative",,"imipramine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","olanzapine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/309f8ac3-a3fd-4313-96aa-7f21fa9cd646.html","2016-05-10 13:11:45 -0400","DDI-clinical-trial","evidence-challenges"," 12.4 Drug Interactions ","Bupropion (a CYP2B6 substrate): Co-administration of a single dose of 150 mg Bupropion Hydrochloride XL with steady state quazepam did not significantly affect the AUC and Cmax of bupropion or its primary metabolite, hydroxybupropion.","","ncit:negative","ncit:quantitative","did not significantly affect the AUC and Cmax of bupropion or its primary metabolite, hydroxybupropion.","quazepam","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","hydroxybupropion","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","150","SD","Oral","1","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 12:34:19 -0700","DDI-clinical-trial","evidence-supports"," —"," Carbamazepine therapy (200 mg bid) causes an approximately 50% increase in the clearance of olanzapine. ","This increase is likely due to the fact that","ncit:positive","ncit:quantitative",,"Carbamazepine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","olanzapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","50","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/50914a46-eab6-4c83-97cf-6ab0234c8126.html","2016-05-10 12:55:04 -0400","DDI-clinical-trial","evidence-challenges","Drug interaction with fluoxetine ","A multiple-dose study was conducted to assess the effect of fluoxetine 20 mg BID on the pharmacokinetics of estazolam 2 mg QHS after seven days. The pharmacokinetics of estazolam (Cmax and AUC) were not affected during multiple-dose fluoxetine, suggesting no clinically significant pharmacokinetic interaction.","","ncit:negative","ncit:quantitative","pharmacokinetics of estazolam (Cmax and AUC) were not affected","estazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","2","fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","QD","Oral","7","BID","Oral","7","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 13:30:19 -0700","DDI-clinical-trial","evidence-challenges"," Imipramine — ","Single doses of olanzapine did not affect the pharmacokinetics of imipramine or its active metabolite desipramine.","","ncit:negative","ncit:quantitative",,"olanzapine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","desipramine","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","SD","Oral","1","UNK","UNKUNUNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:37:25 -0700","DDI-clinical-trial","evidence-supports","exposure may increase bleeding risk. ","Ketoconazole (combined P-gp and strong CYP3A4 inhibitor): Steady-state rivaroxaban AUC and Cmax increased by 160% and 70%, respectively. Similar increases in pharmacodynamic effects were also observed.","","ncit:positive","ncit:quantitative",,"rivaroxaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","Ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","160","Percent","Increase","UNK","UNK","UNK","70","Percent","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 16:08:16 -0700","drug-drug-interaction","evidence-supports","is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. ","Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin. (See CONTRAINDICATIONS, WARNINGS, Myopathy/Rhabdomyolysis, and CLINICAL PHARMACOLOGY, Pharmacokinetics.)","","ncit:positive","ncit:Qualitative","Ketoconazole is a strong inhibitor of CYP3A4 and reduces the elimination of lovastatin","ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"lovastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 13:26:49 -0800","DDI-clinical-trial","evidence-challenges"," This change is of unknown clinical significance."," Pharmacodynamic effects of haloperidol were generally not altered significantly. There were no changes in the pharmacokinetic parameters for nefazodone",". Dosage adjustment of","ncit:negative","ncit:quantitative",,"nefazodone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","200","haloperidol","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","5","BID","Oral","UNK","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:22:15 -0700","drug-drug-interaction","evidence-supports","","Results from drug interaction studies and population PK analyses from clinical studies indicate coadministration of XARELTO with a combined P-gp and strong CYP3A4 inducer (e.g., rifampicin, phenytoin) decreased rivaroxaban exposure by up to 50%."," Similar decreases in pharmacodynamic effects were also observed. These decreases in exposure to","ncit:positive","ncit:Qualitative","decreased rivaroxaban exposure by up to 50%.","rivaroxaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","phenytoin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/7d1a9689-23c8-44ef-a474-8c607e13d794.html","2016-03-14 15:46:58 -0400","drug-drug-interaction","evidence-supports","As with other antipsychotic agents, it should be noted that haloperidol may be capable of potentiating CNS depressants such as anesthetics, opiates, and alcohol. ","In a study of 12 schizophrenic patients coadministered haloperidol and rifampin, plasma haloperidol levels were decreased by a mean of 70% and mean scores on the Brief Psychiatric Rating Scale were increased from baseline.","","ncit:positive","ncit:Qualitative","plasma haloperidol levels were decreased by a mean of 70%","haloperidol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","rifampin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/309f8ac3-a3fd-4313-96aa-7f21fa9cd646.html","2016-05-10 10:09:49 -0700","DDI-clinical-trial","evidence-challenges"," 12.4 Drug Interactions ","Bupropion (a CYP2B6 substrate): Co-administration of a single dose of 150 mg Bupropion Hydrochloride XL with steady state quazepam did not significantly affect the AUC and Cmax of bupropion or its primary metabolite, hydroxybupropion.","","ncit:negative","ncit:quantitative","did not significantly affect the AUC and Cmax of bupropion","quazepam","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","Bupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","150","SD","Oral","1","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/39a5dae2-49f7-4662-9eac-aa7b4c7807a4.html","2016-05-09 16:27:24 -0700","DDI-clinical-trial","evidence-supports","","Eszopiclone and lorazepam decreased each other's Cmax by 22%. ","Coadministration of","ncit:positive","ncit:quantitative",,"lorazepam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","Eszopiclone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","22","Percent","Decrease","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 12:20:54 -0800","drug-drug-interaction","evidence-supports"," Immunosuppressive Agents ","There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. Both cyclosporine and tacrolimus are substrates of CYP3A4, and nefazodone is known to inhibit this enzyme. If either cyclosporine or tacrolimus is administered with nefazodone, blood concentrations of the immunosuppressive agent should be monitored and dosage adjusted accordingly.","","ncit:positive","ncit:Qualitative","eports of increased blood concentrations","cyclosporine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 12:14:12 -0800","drug-drug-interaction","evidence-supports","are necessary when the two drugs are given concomitantly. Subsequent dose adjustments should be made on the basis of clinical response. ","Lithium – In 13 healthy subjects the coadministration of nefazodone (200 mg BID) with lithium (500 mg BID) for 5 days (steady-state conditions) was found to be well tolerated. When the two drugs were coadministered, there were no changes in the steady-state pharmacokinetics of either lithium, nefazodone, or its metabolite HO-NEF; however, there were small decreases in the steady-state plasma concentrations of two nefazodone metabolites, mCPP and triazole-dione, which are considered not to be of clinical significance. Therefore, no dosage adjustment of either lithium or nefazodone is required when they are coadministered.","","ncit:positive","ncit:Qualitative","small decreases in the steady-state plasma concentrations which are considered not to be of clinical significance.","mCPP","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","","Lithium","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c6e131fe-e7df-4876-83f7-9156fc4e8228.html","2016-03-14 15:25:58 -0700","DDI-clinical-trial","evidence-supports","TABLE 3. Effect of Co-administered Drugs on the Pharmacokinetics of Atorvastatin ","Co-administered drug and dosing regimen Atorvastatin Dose (mg) Change in AUC* Change in Cmax* * Data given as x-fold change represent a simple ratio between co-administration and atorvastatin alone (i.e., 1-fold = no change). Data given as % change represent % difference relative to atorvastatin alone (i.e., 0% = no change). † See Sections 5.1 and 7 for clinical significance. ‡ The dose of saquinavir plus ritonavir in this study is not the clinically used dose. The increase in atorvastatin exposure when used clinically is likely to be higher than what was observed in this study. Therefore, caution should be applied and the lowest dose necessary should be used. § Greater increases in AUC (up to 2.5 fold) and/or Cmax (up to 71%) have been reported with excessive grapefruit consumption (≥ 750 mL – 1.2 liters per day). ¶ Single sample taken 8–16 h post dose. # Due to the dual interaction mechanism of rifampin, simultaneous co-administration of atorvastatin with rifampin is recommended, as delayed administration of atorvastatin after administration of rifampin has been associated with a significant reduction in atorvastatin plasma concentrations. †Cyclosporine 5.2 mg/kg/day, stable dose 10 mg QD for 28 days ↑ 8.7 fold ↑ 10.7 fold †Tipranavir 500 mg BID/ritonavir 200 mg BID, 7 days 10 mg, SD ↑ 9.4 fold ↑ 8.6 fold †Telaprevir 750 mg q8h, 10 days 20 mg, SD ↑ 7.88 fold ↑ 10.6 fold","","ncit:positive","ncit:quantitative",,"atorvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","10","Telaprevir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","750","SD","Oral","1","Q8","Oral","10","UNK","7.88","Fold","Increase","UNK","UNK","UNK","10.6","Fold","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/49c4105b-e518-481c-a248-6684135f5bc1.html","2015-11-29 18:49:20 -0500","DDI-clinical-trial","evidence-challenges","is not recommended. Digoxin ","Risperidone (0.25 mg twice daily) did not show a clinically relevant effect on the pharmacokinetics of digoxin. Dose adjustment for digoxin is not recommended.","","ncit:negative","ncit:quantitative",,"digoxin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","Risperidone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",".25","UNK","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/39a5dae2-49f7-4662-9eac-aa7b4c7807a4.html","2016-05-09 16:39:00 -0700","drug-drug-interaction","evidence-challenges","","Lorazepam: Coadministration of single doses of eszopiclone and lorazepam did not have clinically relevant effects on the pharmacodynamics or pharmacokinetics of either drug. The lack of a drug interaction following single-dose administration does not predict the complete absence of a pharmacodynamic effect following chronic administration. ","","ncit:negative","ncit:Qualitative","Coadministration of single doses of eszopiclone and lorazepam did not have clinically relevant effects on the pharmacodynamics or pharmacokinetics of either drug","eszopiclone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","lorazepam","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 12:58:57 -0800","DDI-clinical-trial","evidence-supports","Interaction With Triazolobenzodiazepines ","Interaction studies of nefazodone with two triazolobenzodiazepines, i.e., triazolam and alprazolam, metabolized by cytochrome P450 3A4, have revealed substantial and clinically important increases in plasma concentrations of these compounds when administered concomitantly with nefazodone","","ncit:positive","ncit:quantitative","ncreases in plasma concentrations","alprazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/fdbfe194-b845-42c5-bb87-a48118bc72e7.html","2016-03-31 15:44:32 -0400","drug-drug-interaction","evidence-supports","","In two clinical studies, one in normal volunteers and the other in hypercholesterolemic patients, simvastatin 20-40 mg/day modestly potentiated the effect of coumarin anticoagulants: the prothrombin time, reported as International Normalized Ratio (INR), increased from a baseline of 1.7 to 1.8 and from 2.6 to 3.4 in the volunteer and patient studies, respectively. ","With other statins, clinically evident bleeding and/or increased","ncit:positive","ncit:Qualitative","simvastatin modestly increased INR from a baseline of 1.7 to 1.8 and from 2.6 to 3.4 in the volunteer and patient studies respectively.","coumarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","simvastatin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 16:08:19 -0700","drug-drug-interaction","evidence-challenges","Impact of Dabigatran on Other Drugs ","In clinical studies exploring CYP3A4, CYP2C9, P-gp and other pathways, dabigatran did not meaningfully alter the pharmacokinetics of amiodarone, atorvastatin, clarithromycin, diclofenac, clopidogrel, digoxin, pantoprazole, or ranitidine.","","ncit:negative","ncit:Qualitative","dabigatran did not meaningfully alter the pharmacokinetics of pantoprazole","pantoprazole","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","dabigatran","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 16:05:56 -0700","drug-drug-interaction","evidence-challenges","Impact of Dabigatran on Other Drugs ","In clinical studies exploring CYP3A4, CYP2C9, P-gp and other pathways, dabigatran did not meaningfully alter the pharmacokinetics of amiodarone, atorvastatin, clarithromycin, diclofenac, clopidogrel, digoxin, pantoprazole, or ranitidine.","","ncit:negative","ncit:Qualitative","dabigatran did not meaningfully alter the pharmacokinetics of clarithromycin","dabigatran","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"clarithromycin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 15:26:04 -0700","DDI-clinical-trial","evidence-supports","","Verapamil: When dabigatran etexilate was coadministered with oral verapamil, the Cmax and AUC of dabigatran were increased. The extent of increase depends on the formulation of verapamil and timing of administration. If verapamil is present in the gut when dabigatran is taken, it will increase exposure to dabigatran with the greatest increase observed when a single dose of immediate-release verapamil is given one hour prior to dabigatran (AUC increased by a factor of 2.4). If verapamil is given 2 hours after dabigatran, the increase in AUC is negligible."," In the population pharmacokinetics study from RE-LY, no important changes in","ncit:positive","ncit:quantitative","The extent of increase depends on the formulation of verapamil and timing of administration. If verapamil is present in the gut when dabigatran is taken, it will increase exposure to dabigatran with the greatest increase observed when a single dose of immediate-release verapamil is given one hour prior to dabigatran (AUC increased by a factor of 2.4). If verapamil is given 2 hours after dabigatran, the increase in AUC is negligible.","dabigatran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","verapamil","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","Increase","UNK","UNK","UNK","UNK","UNK","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 14:29:38 -0800","DDI-clinical-trial","evidence-challenges","in ‘Poor Metabolizers’ and Potential Interaction With Drugs That Inhibit and/or Are Metabolized by Cytochrome P450 Isozymes. Fluoxetine – "," When fluoxetine (20 mg QD) and nefazodone (200 mg BID) were administered at steady state there were no changes in the pharmacokinetic parameters for fluoxetine or its metabolite, norfluoxetine. Similarly, there were no changes in the pharmacokinetic parameters of nefazodone or HO-NEF; however, the mean AUC levels of the nefazodone metabolites mCPP and triazole-dione increased by 3 to 6 fold and 1.3 fold, respectively","","ncit:negative","ncit:quantitative",,"HO-NEF","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","200","fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","BID","Oral","UNK","QD","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e1e5249-1cb7-4cc2-ad5a-cdeeee2f494f.html","2016-02-16 16:45:41 -0700","drug-drug-interaction","evidence-supports","potentiated the cognitive and motor effects of alcohol in a clinical trial in subjects with selected psychotic disorders, and alcoholic beverages should be limited while taking quetiapine . ","Quetiapine exposure is increased by the prototype CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.). and decreased by the prototype CYP3A4 inducers (e..g, phenytoin, carbamazepine, rifampin, avasimibe, St. John’s wort etc.).","","ncit:positive","ncit:Qualitative","quetiapine exposure is decreased by CYP3A4 inducers","carbamazepine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"Quetiapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/036db1f2-52b3-42a0-acf9-817b7ba8c724.html","2015-12-08 18:52:09 -0700","DDI-clinical-trial","evidence-challenges","did not affect the pharmacokinetics of ziprasidone . ","Ziprasidone at a dose of 40 mg twice daily administered concomitantly with lithium at a dose of 450 mg twice daily for 7 days did not affect the steady-state level or renal clearance of lithium. Ziprasidone dosed adjunctively to lithium in a maintenance trial of bipolar patients did not affect mean therapeutic lithium levels.","","ncit:negative","ncit:quantitative",,"Ziprasidone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","lithium","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","450","BID","Oral","7","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 12:22:19 -0800","drug-drug-interaction","evidence-supports"," Immunosuppressive Agents ","There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. Both cyclosporine and tacrolimus are substrates of CYP3A4, and nefazodone is known to inhibit this enzyme. If either cyclosporine or tacrolimus is administered with nefazodone, blood concentrations of the immunosuppressive agent should be monitored and dosage adjusted accordingly.","","ncit:positive","ncit:Qualitative","eports of increased blood concentrations","tacrolimus","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/fdbfe194-b845-42c5-bb87-a48118bc72e7.html","2016-03-31 12:22:57 -0700","drug-drug-interaction","evidence-supports","is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. ","Elevated plasma levels of HMG-CoA reductase inhibitory activity increases the risk of myopathy and rhabdomyolysis, particularly with higher doses of simvastatin. [See Warnings and Precautions (5.1) and Clinical Pharmacology (12.3).] Concomitant use of drugs labeled as having a strong inhibitory effect on CYP3A4 is contraindicated [see Contraindications (4)]. If treatment with itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with simvastatin must be suspended during the course of treatment.","","ncit:positive","ncit:Qualitative","strong inhibitor of CYP3A4 may elevate simvastatin plasma level","simvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","voriconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e1e5249-1cb7-4cc2-ad5a-cdeeee2f494f.html","2016-02-16 16:34:30 -0700","drug-drug-interaction","evidence-supports","","Quetiapine exposure is increased by the prototype CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.)",". and decreased by the prototype CYP3A4 inducers (e..g,","ncit:positive","ncit:Qualitative","quetiapine exposure is increased by CYP3A4 inhibitors","itraconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"Quetiapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e1e5249-1cb7-4cc2-ad5a-cdeeee2f494f.html","2016-02-16 16:45:41 -0700","drug-drug-interaction","evidence-supports","potentiated the cognitive and motor effects of alcohol in a clinical trial in subjects with selected psychotic disorders, and alcoholic beverages should be limited while taking quetiapine . ","Quetiapine exposure is increased by the prototype CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.). and decreased by the prototype CYP3A4 inducers (e..g, phenytoin, carbamazepine, rifampin, avasimibe, St. John’s wort etc.).","","ncit:positive","ncit:Qualitative","quetiapine exposure is decreased by CYP3A4 inducers","Quetiapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","avasimibe","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c6e131fe-e7df-4876-83f7-9156fc4e8228.html","2016-03-14 15:11:38 -0700","drug-drug-interaction","evidence-supports"," 7.9 Oral Contraceptives ","Co-administration of LIPITOR and an oral contraceptive increased AUC values for norethindrone and ethinyl estradiol [see Clinical Pharmacology (12.3)]. These increases should be considered when selecting an oral contraceptive for a woman taking LIPITOR","","ncit:positive","ncit:Qualitative","Co-administration of LIPITOR and an oral contraceptive increased AUC values for norethindrone and ethinyl estradiol","LIPITOR","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"ethinyl estradiol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:43:26 -0700","drug-drug-interaction","evidence-supports","CYP2D6 and CYP3A4 Inhibitors ","Concomitant treatment with CLOZARIL and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology (12.3)]. Use caution and monitor patients closely when using such inhibitors. Consider reducing the CLOZARIL dose [see Dosage and Administration (2.6)]","","ncit:positive","ncit:Qualitative","Sertraline can increase clozapine levels","sertraline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"clozapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 17:36:33 -0700","drug-drug-interaction","evidence-challenges","."," In a single-dose drug interaction study there were no pharmacokinetic or pharmacodynamic interactions observed after concomitant administration of naproxen or aspirin (acetylsalicylic acid) with XARELTO.","","ncit:negative","ncit:Qualitative","no pharmacokinetic or pharmacodynamic interactions observed after concomitant administration of naproxen or aspirin (acetylsalicylic acid) with XARELTO.","XARELTO","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","aspirin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:41:56 -0700","drug-drug-interaction","evidence-supports","CYP2D6 and CYP3A4 Inhibitors ","Concomitant treatment with CLOZARIL and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology (12.3)]. Use caution and monitor patients closely when using such inhibitors. Consider reducing the CLOZARIL dose [see Dosage and Administration (2.6)]","","ncit:positive","ncit:Qualitative","Fluoxetine can increase clozapine levels","clozapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e1e5249-1cb7-4cc2-ad5a-cdeeee2f494f.html","2016-02-16 16:50:39 -0700","drug-drug-interaction","evidence-supports","","Coadministration of ketoconazole, a potent inhibitor of cytochrome CYP3A4, resulted in significant increase in quetiapine exposure."," The dose of","ncit:positive","ncit:Qualitative","significantly increased quetiapine exposure","quetiapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:47:05 -0800","DDI-clinical-trial","evidence-challenges","are coadministered; plasma level monitoring for digoxin is recommended. ","Propranolol – The coadministration of nefazodone (200 mg BID) and propranolol (40 mg BID) for 5.5 days to healthy male volunteers (n = 18), including 3 poor and 15 extensive CYP2D6 metabolizers, resulted in 30% and 14% reductions in Cmax and AUC of propranolol, respectively, and a 14% reduction in Cmax for the metabolite, 4-hydroxypropranolol. The kinetics of nefazodone, hydroxynefazodone, and triazole-dione were not affected by coadministration of propranolol. However, Cmax, Cmin, and AUC of m-chlorophenylpiperazine were increased by 23%, 54%, and 28%, respectively. No change in initial dose of either drug is necessary and dose adjustments should be made on the basis of clinical response.","","ncit:negative","ncit:quantitative",,"hydroxynefazodone","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","200","propranolol","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","BID","Oral","5.5","BID","Oral","5.5","18","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:21:50 -0700","drug-drug-interaction","evidence-supports","","Results from drug interaction studies and population PK analyses from clinical studies indicate coadministration of XARELTO with a combined P-gp and strong CYP3A4 inducer (e.g., rifampicin, phenytoin) decreased rivaroxaban exposure by up to 50%."," Similar decreases in pharmacodynamic effects were also observed. These decreases in exposure to","ncit:positive","ncit:Qualitative","decreased rivaroxaban exposure by up to 50%.","rifampicin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"rivaroxaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 14:33:34 -0800","DDI-clinical-trial","evidence-supports","in ‘Poor Metabolizers’ and Potential Interaction With Drugs That Inhibit and/or Are Metabolized by Cytochrome P450 Isozymes. Fluoxetine – "," When fluoxetine (20 mg QD) and nefazodone (200 mg BID) were administered at steady state there were no changes in the pharmacokinetic parameters for fluoxetine or its metabolite, norfluoxetine. Similarly, there were no changes in the pharmacokinetic parameters of nefazodone or HO-NEF; however, the mean AUC levels of the nefazodone metabolites mCPP and triazole-dione increased by 3 to 6 fold and 1.3 fold, respectively","","ncit:positive","ncit:quantitative",,"mCPP","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","200","fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","BID","Oral","UNK","QD","Oral","UNK","UNK","3 to 6","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a971ea18-40cf-4a01-b696-180ccc3fddb5.html","2016-02-29 14:04:47 -0700","drug-drug-interaction","evidence-supports","Antihypertensive effects of guanethidine and related compounds may be counteracted when phenothiazines are used concomitantly. ","Concomitant administration of propranolol with phenothiazines results in increased plasma levels of both drugs.","","ncit:positive","ncit:Qualitative","results in increased plasma levels of both drugs","propranolol","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"phenothiazines","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-31 12:54:41 -0700","drug-drug-interaction","evidence-challenges","Pharmacokinetic data in the pediatric population are not available. Drug-Drug Interactions: ","Data from drug-drug interactions studies involving coadministration of gemfibrozil, niacin, itraconazole, erythromycin, tolbutamide or clopidogrel indicate that the PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with any of these drugs.","","ncit:negative","ncit:Qualitative","PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with gemfibrozil","gemfibrozil","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"fluvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 12:34:19 -0700","DDI-clinical-trial","evidence-supports","","Fluvoxamine, a CYP1A2 inhibitor, decreases the clearance of olanzapine. This results in a mean increase in olanzapine Cmax following fluvoxamine of 54% in female nonsmokers and 77% in male smokers. The mean increase in olanzapine AUC is 52% and 108%, respectively."," Lower doses of","ncit:positive","ncit:quantitative","range in AUC and Cmax changes for female nonsmokers and male smokers","fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","olanzapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","52-108","Percent","Increase","UNK","UNK","UNK","54 - 77\\\\n54-77","Percent","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:24:20 -0700","drug-drug-interaction","evidence-challenges",", but there was an additive effect of decreased alertness. ","Similarly, chlorpromazine in combination with zolpidem produced no pharmacokinetic interaction, but there was an additive effect of decreased alertness and psychomotor performance [see Clinical Pharmacology (12.3)].","","ncit:negative","ncit:Qualitative","produced no pharmacokinetic interaction,","zolpidem","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","chlorpromazine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4b0700c9-b417-4c3a-b36f-de461e125bd3.html","2015-11-29 13:36:22 -0700","DDI-clinical-trial","evidence-challenges","","No clinically relevant effect was observed on steady state lithium exposure following coadministration with multiple daily doses of BRINTELLIX."," Multiple doses of","ncit:negative","ncit:quantitative",,"lithium","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","BRINTELLIX","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a971ea18-40cf-4a01-b696-180ccc3fddb5.html","2016-02-29 16:08:19 -0500","drug-drug-interaction","evidence-supports","results in increased plasma levels of both drugs . ","Phenothiazines may lower the convulsive threshold; dosage adjustments of anticonvulsants may be necessary. Potentiation of anticonvulsant effects does not occur. However, it has been reported that phenothiazines may interfere with the metabolism of Dilantin®‡ (phenytoin) and thus precipitate Dilantin (phenytoin) toxicity.","","ncit:positive","ncit:Qualitative","phenothiazines may precipitate Dilantin toxicity","Dilantin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Phenothiazines","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 11:01:28 -0700","drug-drug-interaction","evidence-challenges","and Drug Interactions (7) ] . ","In dedicated studies conducted in healthy subjects, famotidine, atenolol, prasugrel, and enoxaparin did not meaningfully alter the pharmacokinetics of apixaban.","","ncit:negative","ncit:Qualitative","enoxaparin did not meaningfully alter the pharmacokinetics of apixaban","enoxaparin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"apixaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 16:11:19 -0700","drug-drug-interaction","evidence-supports","is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. ","Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin. (See CONTRAINDICATIONS, WARNINGS, Myopathy/Rhabdomyolysis, and CLINICAL PHARMACOLOGY, Pharmacokinetics.)","","ncit:positive","ncit:Qualitative","posaconazole is a strong inhibitor of CYP3A4 and reduces the elimination of lovastatin","lovastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","posaconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 19:19:02 -0400","drug-drug-interaction","evidence-supports","is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. ","Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin. (See CONTRAINDICATIONS, WARNINGS, Myopathy/Rhabdomyolysis, and CLINICAL PHARMACOLOGY, Pharmacokinetics.)","","ncit:positive","ncit:Qualitative","Cobicistat is a strong inhibitor of CYP3A4 and reduces the elimination of lovastatin","lovastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","cobicistat","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 12:06:08 -0800","DDI-clinical-trial","evidence-supports","were increased by 23%, 54%, and 28%, respectively. No change in initial dose of either drug is necessary and dose adjustments should be made on the basis of clinical response. ","HMG-CoA Reductase Inhibitors – When single 40 mg doses of simvastatin or atorvastatin, both substrates of CYP3A4, were given to healthy adult volunteers who had received nefazodone hydrochloride, 200 mg BID for 6 days, approximately 20 fold increases in plasma concentrations of simvastatin and simvastatin acid and 3 to 4 fold increases in plasma concentrations of atorvastatin and atorvastatin lactone were seen. These effects appear to be due to the inhibition of CYP3A4 by nefazodone because, in the same study, nefazodone had no significant effect on the plasma concentrations of pravastatin, which is not metabolized by CYP3A4 to a clinically significant extent","","ncit:positive","ncit:quantitative","entered plasma concentration as AUC","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","atorvastatin lactone","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","40","SD","Oral","1","BID","Oral","6","UNK","3 to 4","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 10:42:44 -0800","DDI-clinical-trial","evidence-challenges","or its metabolite, 2-hydroxy desipramine . ","There were also no changes in the pharmacokinetics of nefazodone or its triazole-dione metabolite, but the AUC and Cmax of mCPP increased by 44% and 48%, respectively, while the AUC of HO-NEF decreased by 19%. No changes in doses of either nefazodone or desipramine are necessary when the two drugs are given concomitantly. Subsequent dose adjustments should be made on the basis of clinical response.","","ncit:negative","ncit:quantitative",,"nefazodone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","150","desipramine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","75","BID","Oral","UNK","QD","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4b0700c9-b417-4c3a-b36f-de461e125bd3.html","2015-11-29 13:44:17 -0700","DDI-clinical-trial","evidence-challenges","","Coadministration of aspirin 150 mg/day with multiple daily doses of BRINTELLIX had no significant inhibitory effect on platelet aggregation or pharmacokinetics of aspirin and salicylic acid [see Drug Interactions (7.4)]."," Patients receiving other drugs that interfere with hemostasis should be carefully monitored when","ncit:negative","ncit:quantitative",,"BRINTELLIX","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","aspirin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","150","Daily","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5429f134-839f-4ffc-9944-55f51238def8.html","2015-12-18 15:57:58 -0500","DDI-clinical-trial","evidence-supports","on the pharmacokinetics of other co-administered drugs are summarized in Figure 2 . ","Coadministration of paroxetine with SAPHRIS caused a two-fold increase in the maximum plasma concentrations and systemic exposure of paroxetine. Asenapine enhances the inhibitory effects of paroxetine on its own metabolism by CYP2D6.","","ncit:positive","ncit:quantitative",,"paroxetine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","SAPHRIS","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","2","Fold","Increase","UNK","UNK","UNK","2","Fold","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 10:44:04 -0800","DDI-clinical-trial","evidence-challenges","or its metabolite, 2-hydroxy desipramine . ","There were also no changes in the pharmacokinetics of nefazodone or its triazole-dione metabolite, but the AUC and Cmax of mCPP increased by 44% and 48%, respectively, while the AUC of HO-NEF decreased by 19%. No changes in doses of either nefazodone or desipramine are necessary when the two drugs are given concomitantly. Subsequent dose adjustments should be made on the basis of clinical response.","","ncit:negative","ncit:quantitative",,"desipramine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","75","triazole-dione","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","150","BID","Oral","UNK","QD","Oral","UNK","UNK","UNK","UNK","UNK","UNKUNUNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 15:35:32 -0700","DDI-clinical-trial","evidence-supports","trough levels were observed in patients who received amiodarone . ","Quinidine: Quinidine was given as a 200 mg dose every 2 hours up to a total dose of 1000 mg. Dabigatran etexilate was given over 3 consecutive days, the last evening dose on Day 3 with or without quinidine pre-dosing. Concomitant quinidine administration increased dabigatran’s AUC and Cmax by 53% and 56%, respectively.","","ncit:positive","ncit:quantitative","Note: quinidine regimen marked as unknown since Q2H up to 1000mg","quinidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","up to 1000","dabigatran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","3","UNK","Oral","UNK","UNK","53","Percent","Increase","UNKUNUNK","UNK","UNK","56","Percent","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2015-11-29 14:46:00 -0700","DDI-clinical-trial","evidence-supports","","Fluoxetine: Co-administration of fluoxetine (20 mg twice daily for 21 days), a potent inhibitor of CYP2D6, with a single 3 mg dose of iloperidone to 23 healthy volunteers, ages 29 to 44 years, who were classified as CYP2D6 extensive metabolizers, increased the AUC of iloperidone and its metabolite P88, by about 2- to 3-fold, and decreased the AUC of its metabolite P95 by one-half. Iloperidone doses should be reduced by one-half when administered with fluoxetine. ","When","ncit:positive","ncit:quantitative",,"P88","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","3","fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","SD","Oral","1","BID","Oral","21","23","2 to 3","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:43:01 -0700","drug-drug-interaction","evidence-supports","CYP2D6 and CYP3A4 Inhibitors ","Concomitant treatment with CLOZARIL and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology (12.3)]. Use caution and monitor patients closely when using such inhibitors. Consider reducing the CLOZARIL dose [see Dosage and Administration (2.6)]","","ncit:positive","ncit:Qualitative","Terbinafine can increase clozapine levels","clozapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","terbinafine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 16:08:43 -0700","drug-drug-interaction","evidence-challenges","Impact of Dabigatran on Other Drugs ","In clinical studies exploring CYP3A4, CYP2C9, P-gp and other pathways, dabigatran did not meaningfully alter the pharmacokinetics of amiodarone, atorvastatin, clarithromycin, diclofenac, clopidogrel, digoxin, pantoprazole, or ranitidine.","","ncit:negative","ncit:Qualitative","dabigatran did not meaningfully alter the pharmacokinetics of ranitidine","ranitidine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","dabigatran","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 18:07:55 -0700","DDI-clinical-trial","evidence-challenges"," is reported to be a weak inhibitor of aldehyde oxidase in rat liver, but its inhibitory effects in human liver are not known."," There is no pharmacokinetic interaction between zaleplon and diphenhydramine following the administration of a single dose (10 mg and 50 mg, respectively) of each drug. However, because both of these compounds have CNS effects, an additive pharmacodynamic effect is possible.","","ncit:negative","ncit:quantitative","no pharmacokinetic interaction between zaleplon and diphenhydramine","diphenhydramine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","50","zaleplon","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","10","SD","Oral","1","SD","Oral","1","UNK","UNK","UNK","UNK","UNKUNUNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-30 15:07:23 -0700","drug-drug-interaction","evidence-supports"," 7.2 Fluconazole ","Administration of fluvastatin 40 mg single dose to healthy volunteers pre-treated with fluconazole for 4 days results in an increase of fluvastatin exposure. Therefore, in patients taking fluconazole, therapy should be limited to fluvastatin 20 mg twice daily [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative","Concomitant fluconazole increases fluvastatin exposure. Details in Section 12 Table 3","fluconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"fluvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:27:07 -0700","drug-drug-interaction","evidence-supports","7.1 Drugs that Inhibit Cytochrome P450 3A4 Enzymes and Drug Transport Systems ","In drug interaction studies evaluating the concomitant use with drugs that are combined P-gp and CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin, erythromycin and fluconazole), increases in rivaroxaban exposure and pharmacodynamic effects (i.e., factor Xa inhibition and PT prolongation) were observed. The increases in exposure ranged from 30% to 160%. Significant increases in rivaroxaban exposure may increase bleeding risk [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative","increases in rivaroxaban exposure","fluconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"rivaroxaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d78e9639-6fab-4a78-8b29-6991a18ae6c6.html","2016-02-19 17:46:51 -0500","drug-drug-interaction","evidence-supports","ity of this enzyme, so-called “poor” metabolizers. Among other populations the prevalence is not known. Poor metabolizers demonstrate higher plasma concentrations of antipsychotic drugs at usual doses, which may correlate with emergence of side effects. ","In one study of 45 elderly patients suffering from dementia treated with perphenazine, the 5 patients who were prospectively identified as poor P450 2D6 metabolizers had reported significantly greater side effects during the first 10 days of treatment than the 40 extensive metabolizers, following which the groups tended to converge. Prospective phenotyping of elderly patients prior to antipsychotic treatment may identify those at risk for adverse events. The concomitant administration of other drugs that inhibit the activity of P450 2D6 may acutely increase plasma concentrations of antipsychotics. Among these are tricyclic antidepressants and selective serotonin reuptake inhibitors, e.g., fluoxetine, sertraline and paroxetine. When prescribing these drugs to patients already receiving antipsychotic therapy, close monitoring is essential and dose reduction may become necessary to avoid toxicity. Lower doses than usually prescribed for either the antipsychotic or the other drug may be required.","","ncit:positive","ncit:Qualitative","may acutely increase plasma concentrations of antipsychotics.","sertraline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"perphenazine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-30 15:11:14 -0700","drug-drug-interaction","evidence-supports"," 7.8 Warfarin ","Bleeding and/or increased prothrombin times have been reported in patients taking coumarin anticoagulants concomitantly with other HMG-CoA reductase inhibitors. Therefore, patients receiving warfarin-type anticoagulants should have their prothrombin times closely monitored when fluvastatin sodium is initiated or the dosage of fluvastatin sodium is changed.","","ncit:positive","ncit:Qualitative","Concomitant fluvastatin and warfarin have been reported to increase prothrombin time","warfarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluvastatin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/fdbfe194-b845-42c5-bb87-a48118bc72e7.html","2016-03-31 12:38:39 -0700","drug-drug-interaction","evidence-supports","is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. ","Elevated plasma levels of HMG-CoA reductase inhibitory activity increases the risk of myopathy and rhabdomyolysis, particularly with higher doses of simvastatin. [See Warnings and Precautions (5.1) and Clinical Pharmacology (12.3).] Concomitant use of drugs labeled as having a strong inhibitory effect on CYP3A4 is contraindicated [see Contraindications (4)]. If treatment with itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with simvastatin must be suspended during the course of treatment.","","ncit:positive","ncit:Qualitative","strong inhibitor of CYP3A4 may elevate simvastatin plasma level","simvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","clarithromycin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/49c4105b-e518-481c-a248-6684135f5bc1.html","2015-11-29 16:36:20 -0700","DDI-clinical-trial","evidence-challenges","is not recommended. Valproate ","Repeated oral doses of risperidone (4 mg once daily) did not affect the pre-dose or average plasma concentrations and exposure (AUC) of valproate (1000 mg/day in three divided doses) compared to placebo (n=21). However, there was a 20% increase in valproate peak plasma concentration (Cmax) after concomitant administration of risperidone. Dose adjustment for valproate is not recommended.","","ncit:negative","ncit:quantitative",,"valproate","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","1000","risperidone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","4","Daily","Oral","UNK","QD","Oral","UNK","21","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1fd0ba23-962e-427f-8b9d-2cf8f64d0f95.html","2016-03-31 11:20:38 -0700","drug-drug-interaction","evidence-supports"," 7.4 Coumarin Anticoagulants ","CRESTOR significantly increased INR in patients receiving coumarin anticoagulants. Therefore, caution should be exercised when coumarin anticoagulants are given in conjunction with CRESTOR. In patients taking coumarin anticoagulants and CRESTOR concomitantly, INR should be determined before starting CRESTOR and frequently enough during early therapy to ensure that no significant alteration of INR occurs [seeWarnings and Precautions (5.3) and Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative","CRESTOR significantly increased INR in patients receiving coumarin anticoagulants. Study details in Section 12 Table 5","CRESTOR","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"coumarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 15:29:51 -0700","DDI-clinical-trial","evidence-supports",". Similar findings were observed in the RE-COVER study. ","Amiodarone: When dabigatran etexilate was coadministered with a single 600 mg oral dose of amiodarone, the dabigatran AUC and Cmax increased by 58% and 50%, respectively. The increase in exposure was mitigated by a 65% increase in the renal clearance of dabigatran in the presence of amiodarone. The increase in renal clearance may persist after amiodarone is discontinued because of amiodarone’s long half-life. In the population pharmacokinetics study from RE-LY, no important changes in dabigatran trough levels were observed in patients who received amiodarone.","","ncit:positive","ncit:quantitative",,"dabigatran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","amiodarone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","UNK","Oral","UNK","SD","Oral","1","UNK","58","Percent","Increase","65","Percent","Increase","50","Percent","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 11:01:28 -0700","drug-drug-interaction","evidence-challenges","and Drug Interactions (7) ] . ","In dedicated studies conducted in healthy subjects, famotidine, atenolol, prasugrel, and enoxaparin did not meaningfully alter the pharmacokinetics of apixaban.","","ncit:negative","ncit:Qualitative","famotidine did not meaningfully alter the pharmacokinetics of apixaban","apixaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","famotidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 16:06:42 -0700","drug-drug-interaction","evidence-supports"," is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. ","Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin. (See CONTRAINDICATIONS, WARNINGS, Myopathy/Rhabdomyolysis, and CLINICAL PHARMACOLOGY, Pharmacokinetics.)","","ncit:positive","ncit:Qualitative","itraconazole is a strong inhibitor of cyP3A4 and reduces elimination of lovastatin","itraconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"lovastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a0da0dba-a56d-486b-a45b-e8a7cdfbeac6.html","2016-05-10 10:32:01 -0700","DDI-clinical-trial","evidence-supports"," Cimetidine ","Coadministration of cimetidine increased the maximum plasma concentration of triazolam by 51%, decreased clearance by 55%, and increased half-life by 68%; caution and consideration of appropriate triazolam dose reduction are recommended.","","ncit:positive","ncit:quantitative",,"cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","triazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","55","Percent","Decrease","51","Percent","Increase","68","Percent","Increase" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:54:42 -0700","drug-drug-interaction","evidence-challenges","","Zolpidem tartrate had no effect on digoxin pharmacokinetics"," and did not affect","ncit:negative","ncit:Qualitative","had no effect on digoxin pharmacokinetics","digoxin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Zolpidem","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 16:00:33 -0700","drug-drug-interaction","evidence-challenges","or the coagulation measures aPTT, ECT, or TT. ","Diclofenac, Ranitidine, and Digoxin: None of these drugs alters exposure to dabigatran.","","ncit:negative","ncit:Qualitative","digoxin does not alter exposure to dabigatran.","Digoxin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"dabigatran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:44:42 -0700","DDI-clinical-trial","evidence-supports","may be due to the relative difference in P-gp inhibition. ","Erythromycin (combined P-gp and moderate CYP3A4 inhibitor): Both the single-dose rivaroxaban AUC and Cmax increased by 30%","","ncit:positive","ncit:quantitative",,"Erythromycin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","rivaroxaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","30","Percent","Increase","UNK","UNK","UNK","30","Percent","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 13:51:32 -0800","DDI-clinical-trial","evidence-supports","","Buspirone – In a study of steady-state pharmacokinetics in healthy volunteers, coadministration of buspirone (2.5 or 5 mg BID) with nefazodone (250 mg BID) resulted in marked increases in plasma buspirone concentrations (increases up to 20 fold in Cmax and up to 50 fold in AUC) and statistically significant decreases (about 50%) in plasma concentrations of the buspirone metabolite 1-pyrimidinylpiperazine. ","With 5 mg BID doses of","ncit:positive","ncit:quantitative",,"buspirone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","2.5 or 5","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","250","BID","Oral","UNK","BID","Oral","UNK","UNK","up to 50","Fold","Increase","UNK","UNK","UNK","up to 20","Fold","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 12:56:43 -0800","DDI-clinical-trial","evidence-supports","Interaction With Triazolobenzodiazepines ","Interaction studies of nefazodone with two triazolobenzodiazepines, i.e., triazolam and alprazolam, metabolized by cytochrome P450 3A4, have revealed substantial and clinically important increases in plasma concentrations of these compounds when administered concomitantly with nefazodone.","","ncit:positive","ncit:quantitative","increases in plasma concentrations","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","triazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 12:05:05 -0800","drug-drug-interaction","evidence-supports","","The coadministration of triazolam and nefazodone causes a significant increase in the plasma level of triazolam (see WARNINGS and PRECAUTIONS), and a 75% reduction in the initial triazolam dosage is recommended if the two drugs are to be given together. ","Because not all commercially available dosage forms of triazolam permit a sufficient dosage reduction, the coadministration of","ncit:positive","ncit:Qualitative","increase in the plasma level of triazolam","triazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2016-02-18 18:45:32 -0500","DDI-clinical-trial","evidence-supports","dose could then be increased to the previous level. ","Paroxetine: Co-administration of paroxetine (20 mg/day for 5 to 8 days), a potent inhibitor of CYP2D6, with multiple doses of iloperidone (8 or 12 mg twice daily) to patients with schizophrenia ages 18 to 65 years resulted in increased mean steady-state peak concentrations of iloperidone and its metabolite P88, by about 1.6-fold, and decreased mean steady-state peak concentrations of its metabolite P95 by one-half. Iloperidone doses should be reduced by one-half when administered with paroxetine. ","","ncit:positive","ncit:quantitative",,"P88","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","8 or 12","paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","BID","Oral","UNK","Daily","Oral","5 to 8","UNK","UNK","UNK","UNK","UNK","UNK","UNK","1.6","Fold","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:28:00 -0700","DDI-clinical-trial","evidence-challenges"," Haloperidol ","A study involving haloperidol and zolpidem revealed no effect of haloperidol on the pharmacokinetics or pharmacodynamics of zolpidem. The lack of a drug interaction following single-dose administration does not predict the absence of an effect following chronic administration [see Clinical Pharmacology (12.3)].","","ncit:negative","ncit:quantitative","no effect of haloperidol on the pharmacokinetics or pharmacodynamics of zolpidem.","haloperidol","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","zolpidem","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","SD","Oral","1","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:37:21 -0700","DDI-clinical-trial","evidence-supports","Warnings and Precautions (5.1) ]. ","Following five consecutive nightly doses at bedtime of oral zolpidem tartrate 10 mg in the presence of sertraline 50 mg (17 consecutive daily doses, at 7:00 am, in healthy female volunteers), zolpidem Cmax was significantly higher (43%) and Tmax was significantly decreased (-53%). Pharmacokinetics of sertraline and N-desmethylsertraline were unaffected by zolpidem.","","ncit:positive","ncit:quantitative","max was significantly decreased (-53%).","zolpidem","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","10","sertraline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","50","QD","Oral","5","QD","Oral","17","UNK","UNK","UNK","UNK","UNK","UNK","UNK","43","Percent","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 16:22:18 -0700","DDI-clinical-trial","evidence-challenges"," —"," Olanzapine did not influence the pharmacokinetics of diazepam or its active metabolite N-desmethyldiazepam."," However,","ncit:negative","ncit:quantitative",,"Olanzapine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","diazepam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 10:51:40 -0800","DDI-clinical-trial","evidence-challenges","are necessary when the two drugs are given concomitantly. Subsequent dose adjustments should be made on the basis of clinical response. ","Lithium – In 13 healthy subjects the coadministration of nefazodone (200 mg BID) with lithium (500 mg BID) for 5 days (steady-state conditions) was found to be well tolerated. When the two drugs were coadministered, there were no changes in the steady-state pharmacokinetics of either lithium, nefazodone, or its metabolite HO-NEF; however, there were small decreases in the steady-state plasma concentrations of two nefazodone metabolites, mCPP and triazole-dione, which are considered not to be of clinical significance. Therefore, no dosage adjustment of either lithium or nefazodone is required when they are coadministered.","","ncit:negative","ncit:quantitative",,"Lithium","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","500","nefazodone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","200","BID","Oral","5","BID","Oral","5","13","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:51:10 -0800","DDI-clinical-trial","evidence-supports","are coadministered; plasma level monitoring for digoxin is recommended. ","Propranolol – The coadministration of nefazodone (200 mg BID) and propranolol (40 mg BID) for 5.5 days to healthy male volunteers (n = 18), including 3 poor and 15 extensive CYP2D6 metabolizers, resulted in 30% and 14% reductions in Cmax and AUC of propranolol, respectively, and a 14% reduction in Cmax for the metabolite, 4-hydroxypropranolol. The kinetics of nefazodone, hydroxynefazodone, and triazole-dione were not affected by coadministration of propranolol. However, Cmax, Cmin, and AUC of m-chlorophenylpiperazine were increased by 23%, 54%, and 28%, respectively. No change in initial dose of either drug is necessary and dose adjustments should be made on the basis of clinical response.","","ncit:positive","ncit:quantitative",,"m-chlorophenylpiperazine","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","200","propranolol","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","BID","Oral","5.5","BID","Oral","5.5","18","28","Percent","Increase","UNK","UNK","UNK","23","Percent","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/036db1f2-52b3-42a0-acf9-817b7ba8c724.html","2015-12-08 18:59:13 -0700","DDI-clinical-trial","evidence-challenges","(0.03 mg) and levonorgestrel (0.15 mg). ","Consistent with in vitro results, a study in normal healthy volunteers showed that ziprasidone did not alter the metabolism of dextromethorphan, a CYP2D6 model substrate, to its major metabolite, dextrorphan. There was no statistically significant change in the urinary dextromethorphan/dextrorphan ratio.","","ncit:negative","ncit:quantitative",,"dextrorphan","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","ziprasidone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4b0700c9-b417-4c3a-b36f-de461e125bd3.html","2015-11-29 15:59:31 -0500","DDI-clinical-trial","evidence-challenges","), and CYP2C19 (e.g., diazepam), had no clinical meaningful effect on the pharmacokinetics of these substrates (Figure 2) . ","Because vortioxetine is highly bound to plasma protein, coadministration of BRINTELLIX with another drug that is highly protein bound may increase free concentrations of the other drug. However, in a clinical study with coadministration of BRINTELLIX (10 mg/day) and warfarin (1 mg/day to 10 mg/day), a highly protein-bound drug, no significant change in INR was observed [see Drug Interactions (7.2)].","","ncit:negative","ncit:quantitative",,"warfarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","1 to 10","BRINTELLIX","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","Daily","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 15:55:48 -0700","DDI-clinical-trial","evidence-supports"," Other Drugs ","Clopidogrel: When dabigatran etexilate was given concomitantly with a loading dose of 300 mg or 600 mg clopidogrel, the dabigatran AUC and Cmax increased by approximately 30% and 40%, respectively. The concomitant administration of dabigatran etexilate and clopidogrel resulted in no further prolongation of capillary bleeding times compared to clopidogrel monotherapy. When comparing combined treatment and the respective mono-treatments, the coagulation measures for dabigatran’s effect (aPTT, ECT, and TT) remained unchanged, and inhibition of platelet aggregation (IPA), a measurement of clopidogrel’s effect, remained unchanged.","","ncit:positive","ncit:quantitative",,"clopidogrel","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","300 or 600","dabigatran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","SD","Oral","1","UNK","30","Percent","Increase","UNK","UNK","UNK","40","Percent","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-02-18 18:51:21 -0500","DDI-clinical-trial","evidence-supports","Drug-Drug Interaction Studies Fluvoxamine ","A pharmacokinetic study was conducted in 16 schizophrenic patients who received clozapine under steady-state conditions. After coadministration of fluvoxamine for 14 days, mean trough concentrations of clozapine and its metabolites, N-desmethylclozapine and clozapine N-oxide, were elevated about 3-fold compared to baseline steady-state concentrations","","ncit:positive","ncit:quantitative",,"clozapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","14","16","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/7b8e5b26-b9e4-4704-921b-3c3c0d159916.html","2015-11-29 16:18:02 -0700","DDI-clinical-trial","evidence-supports","","Co-administration of INVEGA® 6 mg once daily with carbamazepine, a strong inducer of both CYP3A4 and P-glycoprotein (P-gp), at 200 mg twice daily caused a decrease of approximately 37% in the mean steady-state Cmax and AUC of paliperidone. This decrease is caused, to a substantial degree, by a 35% increase in renal clearance of paliperidone. A minor decrease in the amount of drug excreted unchanged in the urine suggests that there was little effect on the CYP metabolism or bioavailability of paliperidone during carbamazepine co-administration."," On initiation of","ncit:positive","ncit:quantitative",,"carbamazepine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","INVEGA","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","6","QD","Oral","UNK","BID","Oral","UNK","UNK","37","Percent","Decrease","35","Percent","Increase","37","Percent","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/44dcbf97-99ec-427c-ba50-207e0069d6d2.html","2016-03-31 10:14:00 -0700","drug-drug-interaction","evidence-supports"," 7.1 Cyclosporine ","Cyclosporine significantly increased pitavastatin exposure. Co-administration of cyclosporine with LIVALO is contraindicated [see Contraindications (4) and Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative","Cyclosporine significantly increased pitavastatin exposure. Study details in Section 12 Table 3","Cyclosporine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"pitavastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 10:40:46 -0800","DDI-clinical-trial","evidence-challenges","","Desipramine – When nefazodone (150 mg BID) and desipramine (75 mg QD) were administered together there were no changes in the pharmacokinetics of desipramine or its metabolite, 2-hydroxy desipramine. ","There were also no changes in the pharmacokinetics of","ncit:negative","ncit:quantitative",,"nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","150","Desipramine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","75","QD","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 17:32:41 -0700","DDI-clinical-trial","evidence-challenges","."," In another study, single doses of warfarin (15 mg) and XARELTO (5 mg) resulted in an additive effect on factor Xa inhibition and PT. Warfarin did not affect the pharmacokinetics of rivaroxaban.","","ncit:negative","ncit:quantitative","Warfarin did not affect the pharmacokinetics of rivaroxaban","rivaroxaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","5","warfarin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","15","SD","Oral","1","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a0da0dba-a56d-486b-a45b-e8a7cdfbeac6.html","2016-05-10 10:37:18 -0700","DDI-clinical-trial","evidence-supports"," Isoniazid ","Coadministration of isoniazid increased the maximum plasma concentration of triazolam by 20%, decreased clearance by 42%, and increased half-life by 31%.","","ncit:positive","ncit:quantitative",,"isoniazid","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","triazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","42","Percent","Decrease","20","Percent","Increase","31","Percent","Increase" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 17:39:20 -0700","DDI-clinical-trial","evidence-challenges","did not affect the pharmacokinetics of ethanol . ","Imipramine: Coadministration of single doses of Zaleplon 20 mg and imipramine 75 mg produced additive effects on decreased alertness and impaired psychomotor performance for 2 to 4 hours after administration. The interaction was pharmacodynamic with no alteration of the pharmacokinetics of either drug","","ncit:negative","ncit:quantitative","no alteration of the pharmacokinetics of either drug","Zaleplon","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","imipramine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","75","SD","Oral","1","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4b0700c9-b417-4c3a-b36f-de461e125bd3.html","2015-11-29 13:38:00 -0700","DDI-clinical-trial","evidence-challenges","","Multiple doses of BRINTELLIX did not affect the pharmacokinetics or pharmacodynamics (composite cognitive score) of diazepam."," A clinical study has shown that","ncit:negative","ncit:quantitative",,"diazepam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","BRINTELLIX","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/fdbfe194-b845-42c5-bb87-a48118bc72e7.html","2016-03-31 12:22:33 -0700","drug-drug-interaction","evidence-supports","is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. ","Elevated plasma levels of HMG-CoA reductase inhibitory activity increases the risk of myopathy and rhabdomyolysis, particularly with higher doses of simvastatin. [See Warnings and Precautions (5.1) and Clinical Pharmacology (12.3).] Concomitant use of drugs labeled as having a strong inhibitory effect on CYP3A4 is contraindicated [see Contraindications (4)]. If treatment with itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with simvastatin must be suspended during the course of treatment.","","ncit:positive","ncit:Qualitative","strong inhibitor of CYP3A4 may elevate simvastatin plasma level","posaconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"simvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 20:54:45 -0400","DDI-clinical-trial","evidence-challenges","Drugs that are Substrates of CYP3A4 and/or Drug Transport Systems ","In addition, there were no significant pharmacokinetic interactions observed in studies comparing concomitant rivaroxaban 20 mg and 7.5 mg single dose of midazolam (substrate of CYP3A4), 0.375 mg once-daily dose of digoxin (substrate of P-gp), or 20 mg once daily dose of atorvastatin (substrate of CYP3A4 and P-gp) in healthy volunteers.","","ncit:negative","ncit:quantitative","no significant pharmacokinetic interactions observed","atorvastatin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","rivaroxaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","20","UNK","Oral","UNK","QD","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 13:03:19 -0800","DDI-clinical-trial","evidence-challenges","half-life and AUC increased 4 fold and peak concentrations increased 1.7 fold. ","Nefazodone plasma concentrations were unaffected by triazolam.","","ncit:negative","ncit:quantitative",,"Nefazodone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","200","triazolam","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",".25","BID","Oral","UNK","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 17:41:00 -0700","DDI-clinical-trial","evidence-challenges"," Clopidogrel ","In two drug interaction studies where clopidogrel (300 mg loading dose followed by 75 mg daily maintenance dose) and XARELTO (15 mg single dose) were coadministered in healthy subjects, an increase in bleeding time to 45 minutes was observed in approximately 45% and 30% of subjects in these studies, respectively. The change in bleeding time was approximately twice the maximum increase seen with either drug alone. There was no change in the pharmacokinetics of either drug.","","ncit:negative","ncit:quantitative","There was no change in the pharmacokinetics of either drug.","XARELTO","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","15","clopidogrel","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","75","SD","Oral","1","QD","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/036db1f2-52b3-42a0-acf9-817b7ba8c724.html","2015-12-08 19:04:34 -0700","DDI-clinical-trial","evidence-challenges","in a maintenance trial of bipolar patients did not affect mean therapeutic valproate levels. ","Population pharmacokinetic analysis of schizophrenic patients enrolled in controlled clinical trials has not revealed evidence of any clinically significant pharmacokinetic interactions with benztropine, propranolol, or lorazepam. The absolute bioavailability of a 20 mg dose under fed conditions is approximately 60%. The absorption of ziprasidone is increased up to two-fold in the presence of food","","ncit:negative","ncit:quantitative",,"benztropine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","ziprasidone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:05:41 -0800","DDI-clinical-trial","evidence-challenges"," Cimetidine ","When nefazodone (200 mg BID) and cimetidine (300 mg QID) were coadministered for one week, no change in the steady-state pharmacokinetics of either nefazodone or cimetidine was observed compared to each dosed alone. Therefore, dosage adjustment is not necessary for either drug when coadministered.","","ncit:negative","ncit:quantitative",,"cimetidine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","300","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","QID","Oral","7","BID","Oral","7","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/49c4105b-e518-481c-a248-6684135f5bc1.html","2015-11-29 16:36:20 -0700","DDI-clinical-trial","evidence-challenges","Risperidone on other drugs Lithium ","Repeated oral doses of risperidone (3 mg twice daily) did not affect the exposure (AUC) or peak plasma concentrations (Cmax) of lithium (n=13). Dose adjustment for lithium is not recommended.","","ncit:negative","ncit:quantitative",,"lithium","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","risperidone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","3","UNK","Oral","UNK","BID","Oral","UNK","13","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/44dcbf97-99ec-427c-ba50-207e0069d6d2.html","2016-03-31 10:15:25 -0700","drug-drug-interaction","evidence-supports"," 7.2 Erythromycin ","Erythromycin significantly increased pitavastatin exposure. In patients taking erythromycin, a dose of LIVALO 1 mg once daily should not be exceeded [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)]. ","","ncit:positive","ncit:Qualitative","rythromycin significantly increased pitavastatin exposure. Study details in Section 12 Table 3","pitavastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","erythromycin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 12:37:44 -0700","DDI-clinical-trial","evidence-supports","","Fluoxetine (60 mg single dose or 60 mg daily dose for 8 days) causes a small (mean 16%) increase in the maximum concentration of olanzapine and a small (mean 16%) decrease in olanzapine clearance",". The magnitude of the impact of this factor is small in comparison to the overall variability between individuals, and therefore dose modification is not routinely recommended. When using","ncit:positive","ncit:quantitative",,"Fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","60","olanzapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","QD","Oral","8","UNK","UNKUNK","UNK","UNK","16","Percent","Decrease","16","Percent","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 10:49:34 -0700","drug-drug-interaction","evidence-supports","7.2 Strong Dual Inducers of CYP3A4 and P-gp ","Avoid concomitant use of ELIQUIS with strong dual inducers of CYP3A4 and P-gp (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort) because such drugs will decrease exposure to apixaban [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative","carbamezepine will decrease exposure to apixaban","carbamazepine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"apixaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 17:43:16 -0700","DDI-clinical-trial","evidence-challenges"," Clopidogrel ","In two drug interaction studies where clopidogrel (300 mg loading dose followed by 75 mg daily maintenance dose) and XARELTO (15 mg single dose) were coadministered in healthy subjects, an increase in bleeding time to 45 minutes was observed in approximately 45% and 30% of subjects in these studies, respectively. The change in bleeding time was approximately twice the maximum increase seen with either drug alone. There was no change in the pharmacokinetics of either drug.","","ncit:negative","ncit:quantitative","There was no change in the pharmacokinetics of either drug.","clopidogrel","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","15","XARELTO","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","75","SD","UNK","1","QD","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 13:57:09 -0800","DDI-clinical-trial","evidence-supports","and alcohol in depressed patients is not advised. ","Buspirone – In a study of steady-state pharmacokinetics in healthy volunteers, coadministration of buspirone (2.5 or 5 mg BID) with nefazodone (250 mg BID) resulted in marked increases in plasma buspirone concentrations (increases up to 20 fold in Cmax and up to 50 fold in AUC) and statistically significant decreases (about 50%) in plasma concentrations of the buspirone metabolite 1-pyrimidinylpiperazine.","","ncit:positive","ncit:quantitative",,"nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","250","1-pyrimidinylpiperazine.","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","2.5 or 5","BID","Oral","UNK","BID","Oral","UNK","UNK","about 50","Percent","Decrease","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/39a5dae2-49f7-4662-9eac-aa7b4c7807a4.html","2016-05-09 16:28:30 -0700","DDI-clinical-trial","evidence-supports",", but a pharmacodynamic interaction was seen on a measure of psychomotor function. ","Eszopiclone and lorazepam decreased each other's Cmax by 22%. ","","ncit:positive","ncit:quantitative",,"Eszopiclone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","lorazepam","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","22","Percent","Decrease","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1fd0ba23-962e-427f-8b9d-2cf8f64d0f95.html","2016-03-31 11:07:53 -0700","DDI-clinical-trial","evidence-supports"," 7.1 Cyclosporine ","Cyclosporine increased rosuvastatin exposure (AUC) 7‑fold. Therefore, in patients taking cyclosporine, the dose of CRESTOR should not exceed 5 mg once daily [seeDosage and Administration (2.5), Warnings and Precautions (5.1), and Clinical Pharmacology (12.3)].","","ncit:positive","ncit:quantitative","Study details in section 12 Table 4","cyclosporine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","rosuvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","7","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-12 13:35:35 -0400","drug-drug-interaction","evidence-challenges","."," Diclofenac, Ranitidine, and Digoxin: None of these drugs alters exposure to dabigatran.","","ncit:negative","ncit:Qualitative","diclofenac does not alter exposure to dabigatran","dabigatran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Diclofenac","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 14:24:30 -0800","DDI-clinical-trial","evidence-challenges"," –"," When fluoxetine (20 mg QD) and nefazodone (200 mg BID) were administered at steady state there were no changes in the pharmacokinetic parameters for fluoxetine or its metabolite, norfluoxetine."," Similarly, there were no changes in the pharmacokinetic parameters of","ncit:negative","ncit:quantitative",,"fluoxetine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","20","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","QD","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:26:31 -0700","drug-drug-interaction","evidence-supports","7.1 Drugs that Inhibit Cytochrome P450 3A4 Enzymes and Drug Transport Systems ","In drug interaction studies evaluating the concomitant use with drugs that are combined P-gp and CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin, erythromycin and fluconazole), increases in rivaroxaban exposure and pharmacodynamic effects (i.e., factor Xa inhibition and PT prolongation) were observed. The increases in exposure ranged from 30% to 160%. Significant increases in rivaroxaban exposure may increase bleeding risk [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative","increases in rivaroxaban exposure","ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"rivaroxaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 16:22:18 -0700","DDI-clinical-trial","evidence-challenges"," — ","Single doses of olanzapine did not affect the pharmacokinetics of warfarin ","","ncit:negative","ncit:quantitative",,"warfarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","olanzapine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/9c4bedb4-2d59-4fcd-aad7-fce988cd96d8.html","2016-02-29 14:20:40 -0700","drug-drug-interaction","evidence-supports","Thioridazine hydrochloride tablet use should be avoided in combination with other drugs that are known to prolong the QTc interval and in patients with congenital long QT syndrome or a history of cardiac arrhythmias. ","Reduced cytochrome P450 2D6 isozyme activity drugs that inhibit this isozyme (e.g., fluoxetine and paroxetine) and certain other drugs (e.g., fluvoxamine, propranolol, and pindolol) appear to appreciably inhibit the metabolism of thioridazine. The resulting elevated levels of thioridazine would be expected to augment the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as Torsades de pointes type arrhythmias.","","ncit:positive","ncit:Qualitative","appear to appreciably inhibit the metabolism of thioridazine and result in elevated levels of thioridazine","thioridazine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:38:01 -0700","drug-drug-interaction","evidence-supports","concomitantly with drugs that are inducers or inhibitors of these enzymes. CYP1A2 Inhibitors ","Concomitant use of CLOZARIL and CYP1A2 inhibitors can increase plasma levels of clozapine, potentially resulting in adverse reactions. Reduce the CLOZARIL dose to one-third of the original dose when CLOZARIL is coadministered with strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin, or enoxacin). The CLOZARIL dose should be increased to the original dose when coadministration of strong CYP1A2 inhibitors is discontinued [see Dosage and Administration (2.6), Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative","enoxacin can increase clozapine levels","enoxacin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"clozapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4b0700c9-b417-4c3a-b36f-de461e125bd3.html","2015-11-29 13:52:49 -0700","DDI-clinical-trial","evidence-challenges"," is unlikely to induce the metabolism of drugs metabolized by these CYP isoforms. ","Furthermore, in a series of clinical drug interaction studies, coadministration of BRINTELLIX with substrates for CYP2B6 (e.g., bupropion), CYP2C9 (e.g., warfarin), and CYP2C19 (e.g., diazepam), had no clinical meaningful effect on the pharmacokinetics of these substrates (Figure 2).","","ncit:negative","ncit:quantitative",,"bupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","BRINTELLIX","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:36:49 -0700","drug-drug-interaction","evidence-supports","C","oncomitant use of CLOZARIL and CYP1A2 inhibitors can increase plasma levels of clozapine, potentially resulting in adverse reactions. Reduce the CLOZARIL dose to one-third of the original dose when CLOZARIL is coadministered with strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin, or enoxacin). The CLOZARIL dose should be increased to the original dose when coadministration of strong CYP1A2 inhibitors is discontinued [see Dosage and Administration (2.6), Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative","Fluvoxamine can increase clozapine levels","clozapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 17:35:47 -0700","DDI-clinical-trial","evidence-challenges",", reflecting the absence of a role of CYP2D6 in zaleplon 's metabolism. ","Thioridazine: Coadministration of single doses of Zaleplon 20 mg and thioridazine 50 mg produced additive effects on decreased alertness and impaired psychomotor performance for 2 to 4 hours after administration. The interaction was pharmacodynamic with no alteration of the pharmacokinetics of either drug.","","ncit:negative","ncit:quantitative","no alteration of the pharmacokinetics of either drug.","thioridazine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","50","Zaleplon","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","20","SD","Oral","1","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 15:21:53 -0700","DDI-clinical-trial","evidence-supports","is administered 2 hours after dabigatran etexilate . ","Ketoconazole: Systemic ketoconazole increased dabigatran AUC and Cmax values by 138% and 135%, respectively, after a single dose of 400 mg, and 153%, and 149%, respectively, after multiple daily doses of 400 mg.","","ncit:positive","ncit:quantitative","This is multiple ketoconazole doses","ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","400","dabigatran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","QD","Oral","UNK","UNK","153","Percent","Increase","UNK","UNK","UNK","149","Percent","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 13:33:28 -0800","DDI-clinical-trial","evidence-challenges","may be necessary when coadministered with nefazodone . ","Lorazepam – When lorazepam (2 mg BID) and nefazodone (200 mg BID) were coadministered to steady state, there was no change in any pharmacokinetic parameter for either drug compared to each drug administered alone. Therefore, dosage adjustment is not necessary for either drug when coadministered.","","ncit:negative","ncit:quantitative",,"nefazodone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","200","Lorazepam","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","2","BID","Oral","UNK","BID","Oral","UNK","UNK","UNKUNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 15:57:08 -0700","drug-drug-interaction","evidence-challenges","lovastatin and propranolol . ","Digoxin: In patients with hypercholesterolemia, concomitant administration of lovastatin and digoxin resulted in no effect on digoxin plasma concentrations","","ncit:negative","ncit:Qualitative","concomitant administration of lovastatin and digoxin resulted in no effect on digoxin plasma concentrations","lovastatin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"digoxin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/036db1f2-52b3-42a0-acf9-817b7ba8c724.html","2015-12-08 19:05:25 -0700","DDI-clinical-trial","evidence-challenges","in a maintenance trial of bipolar patients did not affect mean therapeutic valproate levels. ","Population pharmacokinetic analysis of schizophrenic patients enrolled in controlled clinical trials has not revealed evidence of any clinically significant pharmacokinetic interactions with benztropine, propranolol, or lorazepam. The absolute bioavailability of a 20 mg dose under fed conditions is approximately 60%. The absorption of ziprasidone is increased up to two-fold in the presence of food","","ncit:negative","ncit:quantitative",,"ziprasidone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","lorazepam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2015-11-29 14:55:02 -0700","DDI-clinical-trial","evidence-supports","dose could then be increased to the previous level. ","Paroxetine: Co-administration of paroxetine (20 mg/day for 5 to 8 days), a potent inhibitor of CYP2D6, with multiple doses of iloperidone (8 or 12 mg twice daily) to patients with schizophrenia ages 18 to 65 years resulted in increased mean steady-state peak concentrations of iloperidone and its metabolite P88, by about 1.6-fold, and decreased mean steady-state peak concentrations of its metabolite P95 by one-half. Iloperidone doses should be reduced by one-half when administered with paroxetine. ","","ncit:positive","ncit:quantitative",,"P95","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","8 or 12","paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","BID","Oral","UNK","Daily","Oral","5 to 8","UNK","UNK","UNK","UNK","UNK","UNK","UNK","50","Percent","Decrease","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 14:01:56 -0800","DDI-clinical-trial","evidence-supports","","With 5 mg BID doses of buspirone, slight increases in AUC were observed for nefazodone (23%) and its metabolites hydroxynefazodone (17%) and mCPP (9%)."," Subjects receiving","ncit:positive","ncit:quantitative",,"buspirone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","5","nefazodone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","250","BID","Oral","UNK","BID","Oral","UNK","UNK","23","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2015-11-29 14:46:00 -0700","DDI-clinical-trial","evidence-supports","","Fluoxetine: Co-administration of fluoxetine (20 mg twice daily for 21 days), a potent inhibitor of CYP2D6, with a single 3 mg dose of iloperidone to 23 healthy volunteers, ages 29 to 44 years, who were classified as CYP2D6 extensive metabolizers, increased the AUC of iloperidone and its metabolite P88, by about 2- to 3-fold, and decreased the AUC of its metabolite P95 by one-half. Iloperidone doses should be reduced by one-half when administered with fluoxetine. ","When","ncit:positive","ncit:quantitative",,"fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","iloperidone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","3","SD","Oral","1","BID","Oral","21","23","2 to 3","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1fd0ba23-962e-427f-8b9d-2cf8f64d0f95.html","2016-03-31 14:25:54 -0400","drug-drug-interaction","evidence-challenges"," 7.6 Fenofibrate ","When CRESTOR was coadministered with fenofibrate, no clinically significant increase in the AUC of rosuvastatin or fenofibrate was observed. Because it is known that the risk of myopathy during treatment with HMG-CoA reductase inhibitors is increased with concomitant use of fenofibrates, caution should be used when prescribing fenofibrates with CRESTOR [seeWarnings and Precautions (5.1) andClinical Pharmacology (12.3)]","","ncit:negative","ncit:Qualitative","When CRESTOR was coadministered with fenofibrate, no clinically significant increase in the AUC of rosuvastatin or fenofibrate was observed.","rosuvastatin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"fenofibrate","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 15:54:45 -0700","drug-drug-interaction","evidence-challenges","","Coumarin Anticoagulants: In a small clinical trial in which lovastatin was administered to warfarin treated patients, no effect on prothrombin time was detected. However, another HMG‑CoA reductase inhibitor has been found to produce a less than two-second increase in prothrombin time in healthy volunteers receiving low doses of warfarin. Also, bleeding and/or increased prothrombin time have been reported in a few patients taking coumarin anticoagulants concomitantly with lovastatin. ","It is recommended that in patients taking anticoagulants,","ncit:negative","ncit:Qualitative","Concomitant lovastatin and warfarin did not effect prothrombin time. But bleeding and increased prothrombin time have been reported with lovastatin and warfarin.","warfarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","lovastatin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:47:42 -0700","DDI-clinical-trial","evidence-supports","AUC and C max increased by 30% . ","Fluconazole (moderate CYP3A4 inhibitor): Single-dose rivaroxaban AUC and Cmax increased by 40% and 30%, respectively.","","ncit:positive","ncit:quantitative",,"rivaroxaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","Fluconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","40","Percent","Increase","UNK","UNK","UNK","30","Percent","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 12:34:19 -0700","drug-drug-interaction","evidence-challenges"," — ","Single doses of cimetidine (800 mg) or aluminum- and magnesium-containing antacids did not affect the oral bioavailability of olanzapine. ","","ncit:negative","ncit:Qualitative","did not affect the oral bioavailability","olanzapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 16:04:29 -0700","drug-drug-interaction","evidence-challenges","Impact of Dabigatran on Other Drugs ","In clinical studies exploring CYP3A4, CYP2C9, P-gp and other pathways, dabigatran did not meaningfully alter the pharmacokinetics of amiodarone, atorvastatin, clarithromycin, diclofenac, clopidogrel, digoxin, pantoprazole, or ranitidine.","","ncit:negative","ncit:Qualitative","dabigatran did not meaningfully alter the pharmacokinetics of amiodarone","amiodarone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","dabigatran","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e1e5249-1cb7-4cc2-ad5a-cdeeee2f494f.html","2016-02-16 18:57:43 -0500","DDI-clinical-trial","evidence-supports","","Coadministration of quetiapine and phenytoin, a CYP3A4 inducer increased the mean oral clearance of quetiapine by 5-fold."," Increased doses of","ncit:positive","ncit:quantitative",,"quetiapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","phenytoin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","5","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4b0700c9-b417-4c3a-b36f-de461e125bd3.html","2015-11-29 13:57:37 -0700","DDI-clinical-trial","evidence-challenges","is unlikely to induce the metabolism of drugs metabolized by these CYP isoforms. ","Furthermore, in a series of clinical drug interaction studies, coadministration of BRINTELLIX with substrates for CYP2B6 (e.g., bupropion), CYP2C9 (e.g., warfarin), and CYP2C19 (e.g., diazepam), had no clinical meaningful effect on the pharmacokinetics of these substrates (Figure 2).","","ncit:negative","ncit:quantitative",,"BRINTELLIX","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","warfarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4b0700c9-b417-4c3a-b36f-de461e125bd3.html","2015-11-29 13:57:37 -0700","DDI-clinical-trial","evidence-challenges","is unlikely to induce the metabolism of drugs metabolized by these CYP isoforms. ","Furthermore, in a series of clinical drug interaction studies, coadministration of BRINTELLIX with substrates for CYP2B6 (e.g., bupropion), CYP2C9 (e.g., warfarin), and CYP2C19 (e.g., diazepam), had no clinical meaningful effect on the pharmacokinetics of these substrates (Figure 2)","","ncit:negative","ncit:quantitative",,"diazepam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","BRINTELLIX","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 14:04:43 -0400","drug-drug-interaction","evidence-challenges","did not meaningfully alter the pharmacokinetics of apixaban . ","In studies conducted in healthy subjects, apixaban did not meaningfully alter the pharmacokinetics of digoxin, naproxen, atenolol, prasugrel, or acetylsalicylic acid.","","ncit:negative","ncit:Qualitative","pixaban did not meaningfully alter the pharmacokinetics of prasugrel","apixaban","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"prasugrel","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/9c4bedb4-2d59-4fcd-aad7-fce988cd96d8.html","2016-02-29 14:40:02 -0700","drug-drug-interaction","evidence-supports"," Propranolol ","Concurrent administration of propranolol (100 to 800 mg daily) has been reported to produce increases in plasma levels of thioridazine (approximately 50% to 400%) and its metabolites (approximately 80% to 300%). Propranolol and thioridazine should not be coadministered.","","ncit:positive","ncit:Qualitative","increases in plasma levels of thioridazine (approximately 50% to 400%) and its metabolites (approximately 80% to 300%)","thioridazine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Propranolol","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 14:55:51 -0700","DDI-clinical-trial","evidence-supports","Impact of Other Drugs on Dabigatran P-gp Inducers ","Rifampin: Rifampin 600 mg once daily for 7 days followed by a single dose of dabigatran decreased its AUC and Cmax by 66% and 67%, respectively. By Day 7 after cessation of rifampin treatment, dabigatran exposure was close to normal [see Warnings and Precautions (5.5) and Drug Interactions (7)].","","ncit:positive","ncit:quantitative",,"dabigatran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","rifampin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","SD","Oral","1","QD","Oral","7","UNK","66","Percent","Decrease","UNK","UNK","UNK","67","Percent","Decrease","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e1e5249-1cb7-4cc2-ad5a-cdeeee2f494f.html","2016-02-16 16:45:41 -0700","drug-drug-interaction","evidence-supports","","Quetiapine exposure is increased by the prototype CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.). and decreased by the prototype CYP3A4 inducers (e..g, phenytoin, carbamazepine, rifampin, avasimibe, St. John’s wort etc.)."," Dose adjustment of","ncit:positive","ncit:Qualitative","quetiapine exposure is decreased by CYP3A4 inducers","phenytoin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"Quetiapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 10:52:47 -0800","DDI-clinical-trial","evidence-challenges","are necessary when the two drugs are given concomitantly. Subsequent dose adjustments should be made on the basis of clinical response. ","Lithium – In 13 healthy subjects the coadministration of nefazodone (200 mg BID) with lithium (500 mg BID) for 5 days (steady-state conditions) was found to be well tolerated. When the two drugs were coadministered, there were no changes in the steady-state pharmacokinetics of either lithium, nefazodone, or its metabolite HO-NEF; however, there were small decreases in the steady-state plasma concentrations of two nefazodone metabolites, mCPP and triazole-dione, which are considered not to be of clinical significance. Therefore, no dosage adjustment of either lithium or nefazodone is required when they are coadministered.","","ncit:negative","ncit:quantitative",,"HO-NEF","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","200","Lithium","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","500","BID","Oral","5","BID","Oral","5","13","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 14:27:03 -0800","DDI-clinical-trial","evidence-challenges","","When fluoxetine (20 mg QD) and nefazodone (200 mg BID) were administered at steady state there were no changes in the pharmacokinetic parameters for fluoxetine or its metabolite, norfluoxetine. Similarly, there were no changes in the pharmacokinetic parameters of nefazodone or HO-NEF; however, the mean AUC levels of the nefazodone metabolites mCPP and triazole-dione increased by 3 to 6 fold and 1.3 fold, respectively."," When a 200 mg dose of","ncit:negative","ncit:quantitative",,"nefazodone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","200","fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","BID","Oral","UNK","QD","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 12:04:34 -0800","DDI-clinical-trial","evidence-supports","were increased by 23%, 54%, and 28%, respectively. No change in initial dose of either drug is necessary and dose adjustments should be made on the basis of clinical response. ","HMG-CoA Reductase Inhibitors – When single 40 mg doses of simvastatin or atorvastatin, both substrates of CYP3A4, were given to healthy adult volunteers who had received nefazodone hydrochloride, 200 mg BID for 6 days, approximately 20 fold increases in plasma concentrations of simvastatin and simvastatin acid and 3 to 4 fold increases in plasma concentrations of atorvastatin and atorvastatin lactone were seen. These effects appear to be due to the inhibition of CYP3A4 by nefazodone because, in the same study, nefazodone had no significant effect on the plasma concentrations of pravastatin, which is not metabolized by CYP3A4 to a clinically significant extent","","ncit:positive","ncit:quantitative","entered plasma concentration as AUC","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","atorvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","40","SD","Oral","1","BID","Oral","6","UNK","3 to 4","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:11:14 -0800","DDI-clinical-trial","evidence-challenges"," Theophylline ","When nefazodone (200 mg BID) was given to patients being treated with theophylline (600 to 1200 mg/day) for chronic obstructive pulmonary disease, there was no change in the steady-state pharmacokinetics of either nefazodone or theophylline. FEV1 measurements taken when theophylline and nefazodone were coadministered did not differ from baseline dosage (i.e., when theophylline was administered alone). Therefore, dosage adjustment is not necessary for either drug when coadministered.","","ncit:negative","ncit:quantitative",,"nefazodone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","200","theophylline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","600 to 1200","BID","Oral","UNK","Daily","Oral","UNK","UNK","UNK","UNK","UNK","UNKUNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 15:02:14 -0700","DDI-clinical-trial","evidence-supports","and AUC are described below. ","Dronedarone: Simultaneous administration of dabigatran etexilate and dronedarone (administered once or twice daily) increases exposure to dabigatran by 70 to 140% compared to dabigatran alone. The increase in exposure is only 30 to 60% higher compared to dabigatran alone when dronedarone is administered 2 hours after dabigatran etexilate","","ncit:positive","ncit:quantitative","The increase in exposure is only 30 to 60% higher compared to dabigatran alone when dronedarone is administered 2 hours after dabigatran etexilate","dabigatran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","dronedarone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","70-1470-140","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:40:35 -0700","DDI-clinical-trial","evidence-challenges","Warnings and Precautions (5.1) ]. ","Following five consecutive nightly doses at bedtime of oral zolpidem tartrate 10 mg in the presence of sertraline 50 mg (17 consecutive daily doses, at 7:00 am, in healthy female volunteers), zolpidem Cmax was significantly higher (43%) and Tmax was significantly decreased (-53%). Pharmacokinetics of sertraline and N-desmethylsertraline were unaffected by zolpidem.","","ncit:negative","ncit:quantitative","Pharmacokinetics of sertraline and N-desmethylsertraline were unaffected by zolpidem.","zolpidem","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","10","N-desmethylsertraline","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","50","QD","Oral","17","QD","Oral","5","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:37:36 -0800","DDI-clinical-trial","evidence-supports","","Propranolol – The coadministration of nefazodone (200 mg BID) and propranolol (40 mg BID) for 5.5 days to healthy male volunteers (n = 18), including 3 poor and 15 extensive CYP2D6 metabolizers, resulted in 30% and 14% reductions in Cmax and AUC of propranolol, respectively, and a 14% reduction in Cmax for the metabolite, 4-hydroxypropranolol."," The kinetics of","ncit:positive","ncit:quantitative",,"nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","propranolol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","40","BID","Oral","5.5","BID","Oral","5.5","18","14","Percent","Decrease","UNK","UNK","UNK","30","Percent","Decrease","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 12:04:34 -0800","DDI-clinical-trial","evidence-supports","were increased by 23%, 54%, and 28%, respectively. No change in initial dose of either drug is necessary and dose adjustments should be made on the basis of clinical response. ","HMG-CoA Reductase Inhibitors – When single 40 mg doses of simvastatin or atorvastatin, both substrates of CYP3A4, were given to healthy adult volunteers who had received nefazodone hydrochloride, 200 mg BID for 6 days, approximately 20 fold increases in plasma concentrations of simvastatin and simvastatin acid and 3 to 4 fold increases in plasma concentrations of atorvastatin and atorvastatin lactone were seen. These effects appear to be due to the inhibition of CYP3A4 by nefazodone because, in the same study, nefazodone had no significant effect on the plasma concentrations of pravastatin, which is not metabolized by CYP3A4 to a clinically significant extent","","ncit:positive","ncit:quantitative","entered plasma concentration as AUC","simvastatin acid","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","200","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","BID","Oral","6","SD","Oral","1","UNK","20","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:39:55 -0700","drug-drug-interaction","evidence-supports","CYP2D6 and CYP3A4 Inhibitors ","Concomitant treatment with CLOZARIL and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology (12.3)]. Use caution and monitor patients closely when using such inhibitors. Consider reducing the CLOZARIL dose [see Dosage and Administration (2.6)].","","ncit:positive","ncit:Qualitative","Erythromycin can increase clozapine levels","erythromycin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"clozapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:43:01 -0700","drug-drug-interaction","evidence-supports","CYP2D6 and CYP3A4 Inhibitors ","Concomitant treatment with CLOZARIL and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology (12.3)]. Use caution and monitor patients closely when using such inhibitors. Consider reducing the CLOZARIL dose [see Dosage and Administration (2.6)]","","ncit:positive","ncit:Qualitative","Duloxetine can increase clozapine levels","clozapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","duloxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/39a5dae2-49f7-4662-9eac-aa7b4c7807a4.html","2016-05-09 16:39:00 -0700","DDI-clinical-trial","evidence-challenges","","Digoxin: A single dose of eszopiclone 3 mg did not affect the pharmacokinetics of digoxin measured at steady state following dosing of 0.5 mg twice daily for one day and 0.25 mg daily for the next 6 days. ","","ncit:negative","ncit:quantitative","digoxin dosing of 0.5 mg twice daily for one day and 0.25 mg daily for the next 6 days","digoxin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction",".25","eszopiclone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","3","Daily","Oral","6","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:30:14 -0700","DDI-clinical-trial","evidence-supports"," Fluoxetine ","After multiple doses of zolpidem tartrate and fluoxetine an increase in the zolpidem half-life (17%) was observed. There was no evidence of an additive effect in psychomotor performance [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:quantitative",,"fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","zolpidem","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","17","Percent","Increase" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 14:07:38 -0800","DDI-clinical-trial","evidence-supports","metabolite 1-pyrimidinylpiperazine. ","With 5 mg BID doses of buspirone, slight increases in AUC were observed for nefazodone (23%) and its metabolites hydroxynefazodone (17%) and mCPP (9%)","","ncit:positive","ncit:quantitative",,"mCPP","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","250","buspirone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","5","BID","Oral","UNK","BID","Oral","UNK","UNK","9","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 15:52:59 -0700","DDI-clinical-trial","evidence-supports","; but ","when ticagrelor 180 mg was given 2 hours after dabigatran, the AUCτ,ss and Cmax,ss of dabigatran increased by only 27% and 24%, respectively [see Warnings and Precautions (5.2) and Drug Interactions (7.1)].","","ncit:positive","ncit:quantitative","ticagrlor given 2 hours after dabigatran resulted in less of AUC and CMAX increases than concomitant dosing","dabigatran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","ticagrelor","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","180","UNK","Oral","UNK","SD","Oral","1","UNK","27","Percent","Increase","UNK","UNK","UNK","24","Percent","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:51:56 -0700","DDI-clinical-trial","evidence-supports","Drugs that Induce Cytochrome P450 3A4 Enzymes and Drug Transport Systems ","In a drug interaction study, coadministration of XARELTO (20 mg single dose with food) with a drug that is a combined P-gp and strong CYP3A4 inducer (rifampicin titrated up to 600 mg once daily) led to an approximate decrease of 50% and 22% in AUC and Cmax, respectively. Similar decreases in pharmacodynamic effects were also observed. These decreases in exposure to rivaroxaban may decrease efficacy.","","ncit:positive","ncit:quantitative",,"rivaroxaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","20","rifampicin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","SD","Oral","1","QD","Oral","UNK","UNK","50","Percent","Decrease","UNK","UNK","UNK","22","Percent","Decrease","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 13:24:14 -0800","DDI-clinical-trial","evidence-supports","","Haloperidol – When a single oral 5 mg dose of haloperidol was coadministered with nefazodone (200 mg BID) at steady state, haloperidol apparent clearance decreased by 35% with no significant increase in peak haloperidol plasma concentrations or time of peak."," This change is of unknown clinical significance. Pharmacodynamic effects of","ncit:positive","ncit:quantitative",,"nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","haloperidol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","5","SD","Oral","1","BID","Oral","UNK","UNK","UNK","UNK","UNK","35","Percent","Decrease","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4b0700c9-b417-4c3a-b36f-de461e125bd3.html","2015-11-29 13:42:04 -0700","DDI-clinical-trial","evidence-challenges","","Following coadministration of stable doses of warfarin (1 to 10 mg/day) with multiple daily doses of BRINTELLIX, no significant effects were observed in INR, prothrombin values or total warfarin (protein bound plus free drug) pharmacokinetics for both R- and S-warfarin [see Drug Interactions (7.4)]."," Coadministration of","ncit:negative","ncit:quantitative",,"BRINTELLIX","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","warfarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","1 to 10","Daily","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/036db1f2-52b3-42a0-acf9-817b7ba8c724.html","2015-12-08 18:57:19 -0700","DDI-clinical-trial","evidence-challenges","in a maintenance trial of bipolar patients did not affect mean therapeutic lithium levels. ","In vivo studies have revealed no effect of ziprasidone on the pharmacokinetics of estrogen or progesterone components. Ziprasidone at a dose of 20 mg twice daily did not affect the pharmacokinetics of concomitantly administered oral contraceptives, ethinyl estradiol (0.03 mg) and levonorgestrel (0.15 mg).","","ncit:negative","ncit:quantitative",,"levonorgestrel","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction",".15","Ziprasidone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","UNK","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/9c4bedb4-2d59-4fcd-aad7-fce988cd96d8.html","2016-02-29 16:44:38 -0500","drug-drug-interaction","evidence-supports"," Pindolol ","Concurrent administration of pindolol and thioridazine have resulted in moderate, dose related increases in the serum levels of thioridazine and two of its metabolites, as well as higher than expected serum pindolol levels. Pindolol and thioridazine should not be coadministered.","","ncit:positive","ncit:Qualitative","concomitant use with thirodazine produced higher than expected serum pindolol levels.","pindolol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","thioridazine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 14:04:43 -0400","drug-drug-interaction","evidence-challenges","did not meaningfully alter the pharmacokinetics of apixaban . ","In studies conducted in healthy subjects, apixaban did not meaningfully alter the pharmacokinetics of digoxin, naproxen, atenolol, prasugrel, or acetylsalicylic acid.","","ncit:negative","ncit:Qualitative","pixaban did not meaningfully alter the pharmacokinetics of acetylsalicylic acid","acetylsalicylic acid","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","apixaban","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:39:55 -0700","drug-drug-interaction","evidence-supports","CYP2D6 and CYP3A4 Inhibitors ","Concomitant treatment with CLOZARIL and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology (12.3)]. Use caution and monitor patients closely when using such inhibitors. Consider reducing the CLOZARIL dose [see Dosage and Administration (2.6)]. ","","ncit:positive","ncit:Qualitative","cimetidine can increase clozapine levels","cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"clozapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5429f134-839f-4ffc-9944-55f51238def8.html","2015-12-18 13:50:52 -0700","DDI-clinical-trial","evidence-supports","CYP2D6 substrates and inhibitors (e.g., paroxetine ) ","SAPHRIS may enhance the inhibitory effects of paroxetine on its own metabolism. Concomitant use of paroxetine with SAPHRIS increased the paroxetine exposure by 2-fold as compared to use paroxetine alone [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:quantitative",,"SAPHRIS","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","paroxetine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","2","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/7b8e5b26-b9e4-4704-921b-3c3c0d159916.html","2015-11-29 16:14:39 -0700","DDI-clinical-trial","evidence-challenges","","In a drug interaction study, co-administration of INVEGA® (12 mg once daily for 5 days) with divalproex sodium extended-release tablets (500 mg to 2000 mg once daily) did not affect the steady-state pharmacokinetics (AUC24h and Cmax,ss) of valproate in 13 patients stabilized on valproate. ","In a clinical study, subjects on stable doses of","ncit:negative","ncit:quantitative",,"divalproex sodium","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","500 to 2000","INVEGA","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","12","QD","Oral","UNK","QD","Oral","5","13","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 16:00:33 -0700","drug-drug-interaction","evidence-challenges","or the coagulation measures aPTT, ECT, or TT. ","Diclofenac, Ranitidine, and Digoxin: None of these drugs alters exposure to dabigatran.","","ncit:negative","ncit:Qualitative","ranitidine does not alter exposure to dabigatran.","dabigatran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Ranitidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 17:30:22 -0700","DDI-clinical-trial","evidence-challenges","did not affect the pharmacokinetics of ethanol . ","Imipramine: Coadministration of single doses of Zaleplon 20 mg and imipramine 75 mg produced additive effects on decreased alertness and impaired psychomotor performance for 2 to 4 hours after administration. The interaction was pharmacodynamic with no alteration of the pharmacokinetics of either drug.","","ncit:negative","ncit:quantitative","with no alteration of the pharmacokinetics of either drug.","imipramine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","75","Zaleplon","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","20","SD","Oral","1","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:41:56 -0700","drug-drug-interaction","evidence-supports","CYP2D6 and CYP3A4 Inhibitors ","Concomitant treatment with CLOZARIL and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology (12.3)]. Use caution and monitor patients closely when using such inhibitors. Consider reducing the CLOZARIL dose [see Dosage and Administration (2.6)]","","ncit:positive","ncit:Qualitative","Bupropion can increase clozapine levels","bupropion","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"clozapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-31 12:57:26 -0700","drug-drug-interaction","evidence-challenges","Pharmacokinetic data in the pediatric population are not available. Drug-Drug Interactions: ","Data from drug-drug interactions studies involving coadministration of gemfibrozil, niacin, itraconazole, erythromycin, tolbutamide or clopidogrel indicate that the PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with any of these drugs.","","ncit:negative","ncit:Qualitative","PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with clopidogrel","clopidogrel","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"fluvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 16:24:02 -0700","DDI-clinical-trial","evidence-challenges","","Olanzapine did not influence the pharmacokinetics of diazepam or its active metabolite N-desmethyldiazepam."," However,","ncit:negative","ncit:quantitative",,"N-desmethyldiazepam.","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","UNK","Olanzapine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:38:58 -0700","DDI-clinical-trial","evidence-challenges","Warnings and Precautions (5.1) ]. ","Following five consecutive nightly doses at bedtime of oral zolpidem tartrate 10 mg in the presence of sertraline 50 mg (17 consecutive daily doses, at 7:00 am, in healthy female volunteers), zolpidem Cmax was significantly higher (43%) and Tmax was significantly decreased (-53%). Pharmacokinetics of sertraline and N-desmethylsertraline were unaffected by zolpidem.","","ncit:negative","ncit:quantitative","Pharmacokinetics of sertraline and N-desmethylsertraline were unaffected by zolpidem.","zolpidem","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","10","sertraline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","50","QD","Oral","1","QD","Oral","5","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-30 15:08:21 -0700","drug-drug-interaction","evidence-supports"," 7.6 Glyburide ","Concomitant administration of fluvastatin and glyburide increased glyburide exposures. Patients on concomitant therapy of glyburide and fluvastatin should continue to be monitored appropriately [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative","Concomitant fluvastatin increases glyburide exposure. Details in Section 12 Table 3","glyburide","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluvastatin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/036db1f2-52b3-42a0-acf9-817b7ba8c724.html","2015-12-08 18:44:10 -0700","DDI-clinical-trial","evidence-supports","and dopamine agonists. Carbamazepine ","Carbamazepine is an inducer of CYP3A4; administration of 200 mg twice daily for 21 days resulted in a decrease of approximately 35% in the AUC of ziprasidone. This effect may be greater when higher doses of carbamazepine are administered. ","","ncit:positive","ncit:quantitative",,"carbamazepine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","ziprasidone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","BID","Oral","21","UNK","35","Percent","Decrease","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/39a5dae2-49f7-4662-9eac-aa7b4c7807a4.html","2016-05-09 16:27:24 -0700","DDI-clinical-trial","evidence-challenges","","Paroxetine: Coadministration of single dose of eszopiclone and paroxetine produced no pharmacokinetic or pharmacodynamic interaction. The lack of a drug interaction following single-dose administration does not predict the complete absence of a pharmacodynamic effect following chronic administration. ","","ncit:negative","ncit:quantitative","Coadministration of single dose of eszopiclone and paroxetine produced no pharmacokinetic or pharmacodynamic interaction.","paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","eszopiclone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","SD","Oral","1","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1fd0ba23-962e-427f-8b9d-2cf8f64d0f95.html","2016-03-31 11:20:38 -0700","drug-drug-interaction","evidence-supports"," 7.2 Gemfibrozil ","Gemfibrozil significantly increased rosuvastatin exposure. Due to an observed increased risk of myopathy/rhabdomyolysis, combination therapy with CRESTOR and gemfibrozil should be avoided. If used together, the dose of CRESTOR should not exceed 10 mg once daily [seeClinical Pharmacology (12.3)]","","ncit:positive","ncit:Qualitative","Gemfibrozil significantly increased rosuvastatin exposure. Study details in Section 12 Table 4","gemfibrozil","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"rosuvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 11:01:28 -0700","drug-drug-interaction","evidence-challenges","and Drug Interactions (7) ] . ","In dedicated studies conducted in healthy subjects, famotidine, atenolol, prasugrel, and enoxaparin did not meaningfully alter the pharmacokinetics of apixaban.","","ncit:negative","ncit:Qualitative","prasugrel did not meaningfully alter the pharmacokinetics of apixaban","apixaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","prasugrel","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 19:19:02 -0400","drug-drug-interaction","evidence-supports","is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. ","Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin. (See CONTRAINDICATIONS, WARNINGS, Myopathy/Rhabdomyolysis, and CLINICAL PHARMACOLOGY, Pharmacokinetics.)","","ncit:positive","ncit:Qualitative","Erythromycin is a strong inhibitor of CYP3A4 and reduces the elimination of lovastatin","erythromycin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"lovastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 16:13:29 -0700","drug-drug-interaction","evidence-supports","is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. ","Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin. (See CONTRAINDICATIONS, WARNINGS, Myopathy/Rhabdomyolysis, and CLINICAL PHARMACOLOGY, Pharmacokinetics.)","","ncit:positive","ncit:Qualitative","voriconazole is a strong inhibitor of CYP3A4 and reduces the elimination of lovastatin","lovastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","voriconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/036db1f2-52b3-42a0-acf9-817b7ba8c724.html","2015-12-08 18:50:07 -0700","DDI-clinical-trial","evidence-challenges","by about 35–40%. Other inhibitors of CYP3A4 would be expected to have similar effects. Cimetidine ","Cimetidine at a dose of 800 mg QD for 2 days did not affect ziprasidone pharmacokinetics.","","ncit:negative","ncit:quantitative",,"ziprasidone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","Cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","800","UNK","Oral","UNK","QD","Oral","2","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2015-12-18 15:38:03 -0700","DDI-clinical-trial","evidence-supports","Drug-Drug Interaction Studies Fluvoxamine ","A pharmacokinetic study was conducted in 16 schizophrenic patients who received clozapine under steady-state conditions. After coadministration of fluvoxamine for 14 days, mean trough concentrations of clozapine and its metabolites, N-desmethylclozapine and clozapine N-oxide, were elevated about 3-fold compared to baseline steady-state concentrations.","","ncit:positive","ncit:quantitative",,"fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","N-desmethylclozapine","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","UNK","UNK","UNK","UNK","UNK","Oral","14","16","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/fdbfe194-b845-42c5-bb87-a48118bc72e7.html","2016-03-31 11:53:44 -0700","DDI-clinical-trial","evidence-supports","is not an inhibitor of CYP3A4, and, therefore, is not expected to affect the plasma levels of other drugs metabolized by CYP3A4. ","Coadministration of simvastatin (40 mg QD for 10 days) resulted in an increase in the maximum mean levels of cardioactive digoxin (given as a single 0.4 mg dose on day 10) by approximately 0.3 ng/mL.","","ncit:positive","ncit:quantitative",,"simvastatin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","digoxin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction",".4","SD","Oral","1","QD","Oral","10","UNK","UNK","UNK","UNK","UNK","UNK","UNK",".3ng//mL","UNK","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/036db1f2-52b3-42a0-acf9-817b7ba8c724.html","2015-12-08 18:55:35 -0700","DDI-clinical-trial","evidence-challenges","in a maintenance trial of bipolar patients did not affect mean therapeutic lithium levels. ","In vivo studies have revealed no effect of ziprasidone on the pharmacokinetics of estrogen or progesterone components. Ziprasidone at a dose of 20 mg twice daily did not affect the pharmacokinetics of concomitantly administered oral contraceptives, ethinyl estradiol (0.03 mg) and levonorgestrel (0.15 mg).","","ncit:negative","ncit:quantitative",,"ethinyl estradiol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction",".03","ziprasidone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","UNK","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:45:30 -0700","DDI-clinical-trial","evidence-challenges","","A single-dose interaction study with zolpidem tartrate 10 mg and fluoxetine 20 mg at steady-state levels in male volunteers did not demonstrate any clinically significant pharmacokinetic or pharmacodynamic interactions. ","When multiple doses of","ncit:negative","ncit:quantitative","id not demonstrate any clinically significant pharmacokinetic or pharmacodynamic interactions","zolpidem","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","10","fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 15:56:19 -0700","drug-drug-interaction","evidence-challenges","WARNINGS, Myopathy/Rhabdomyolysis . ","Propranolol: In normal volunteers, there was no clinically significant pharmacokinetic or pharmacodynamic interaction with concomitant administration of single doses of lovastatin and propranolol.","","ncit:negative","ncit:Qualitative","No clinically significant PK interaction with concomitant lovastatin and propranolol","propranolol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","lovastatin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 16:07:41 -0700","drug-drug-interaction","evidence-challenges","Impact of Dabigatran on Other Drugs ","In clinical studies exploring CYP3A4, CYP2C9, P-gp and other pathways, dabigatran did not meaningfully alter the pharmacokinetics of amiodarone, atorvastatin, clarithromycin, diclofenac, clopidogrel, digoxin, pantoprazole, or ranitidine.","","ncit:negative","ncit:Qualitative","dabigatran did not meaningfully alter the pharmacokinetics of digoxin","dabigatran","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"digoxin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 15:45:57 -0700","DDI-clinical-trial","evidence-supports","","Ticagrelor: Administration of ticagrelor modestly increases plasma concentrations of dabigatran with the magnitude of increase dependent on the dose and timing of ticagrelor administration. When dabigatran etexilate 110 mg twice daily was coadministered with 90 mg oral ticagrelor twice daily, the AUCτ,ss and Cmax,ss of dabigatran increased by 26% and 29%, respectively."," When coadministered with a loading dose of 180 mg","ncit:positive","ncit:quantitative",,"ticagrelor","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","90","dabigatran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","110","BID","Oral","UNK","BID","Oral","UNK","UNK","26","Percent","Increase","UNK","UNK","UNK","29","Percent","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a0da0dba-a56d-486b-a45b-e8a7cdfbeac6.html","2016-05-10 10:40:54 -0700","DDI-clinical-trial","evidence-supports"," Oral contraceptives ","Coadministration of oral contraceptives increased maximum plasma concentration by 6%, decreased clearance by 32%, and increased half-life by 16%. Grapefruit juice Coadministration of grapefruit juice increased the maximum plasma concentration of triazolam","","ncit:positive","ncit:quantitative",,"oral contraceptives","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","triazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","UNK","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","32","Percent","Decrease","6","Percent","Increase","16","Percent","Increase" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ee49f3b1-1650-47ff-9fb1-ea53fe0b92b6.html","2016-03-14 13:58:35 -0700","DDI-clinical-trial","evidence-challenges","aripiprazole pharmacokinetics ","The effects of ABILIFY on the exposures of other drugs are summarized in Figure 21. A population PK analysis in patients with major depressive disorder showed no substantial change in plasma concentrations of fluoxetine (20 mg/day or 40 mg/day), paroxetine CR (37.5 mg/day or 50 mg/day), or sertraline (100 mg/day or 150 mg/day) dosed to steady-state. The steady-state plasma concentrations of fluoxetine and norfluoxetine increased by about 18% and 36%, respectively, and concentrations of paroxetine decreased by about 27%. The steady-state plasma concentrations of sertraline and desmethylsertraline were not substantially changed when these antidepressant therapies were coadministered with aripiprazole.","","ncit:negative","ncit:quantitative","The steady-state plasma concentrations of sertraline and desmethylsertraline were not substantially changed when these antidepressant therapies were coadministered with aripiprazole.","ABILIFY","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","sertraline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","100-150","Daily","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 15:37:23 -0700","drug-drug-interaction","evidence-challenges","by 53% and 56%, respectively. ","Clarithromycin: Coadministered clarithromycin had no impact on the exposure to dabigatran.","","ncit:negative","ncit:Qualitative","clarithromycin had no impact on the exposure to dabigatran","dabigatran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","clarithromycin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 16:15:09 -0700","drug-drug-interaction","evidence-supports","is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. ","Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin. (See CONTRAINDICATIONS, WARNINGS, Myopathy/Rhabdomyolysis, and CLINICAL PHARMACOLOGY, Pharmacokinetics.)","","ncit:positive","ncit:Qualitative","Boceprevir is a strong inhibitor of CYP3A4 and reduces the elimination of lovastatin","lovastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","boceprevir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 10:46:00 -0800","DDI-clinical-trial","evidence-supports","or its metabolite, 2-hydroxy desipramine . ","There were also no changes in the pharmacokinetics of nefazodone or its triazole-dione metabolite, but the AUC and Cmax of mCPP increased by 44% and 48%, respectively, while the AUC of HO-NEF decreased by 19%. No changes in doses of either nefazodone or desipramine are necessary when the two drugs are given concomitantly. Subsequent dose adjustments should be made on the basis of clinical response.","","ncit:positive","ncit:quantitative",,"desipramine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","75","mCPP","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","150","BID","Oral","UNK","QD","Oral","UNK","UNK","44","Percent","Increase","UNK","UNK","UNK","48","Percent","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 12:46:01 -0700","drug-drug-interaction","evidence-supports","Inducers of CYP1A2 or Glucuronyl Transferase — "," Omeprazole and rifampin may cause an increase in olanzapine clearance. ","","ncit:positive","ncit:Qualitative","may cause an increase in olanzapine clearance","olanzapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","rifampin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-31 12:55:20 -0700","drug-drug-interaction","evidence-challenges","Pharmacokinetic data in the pediatric population are not available. Drug-Drug Interactions: ","Data from drug-drug interactions studies involving coadministration of gemfibrozil, niacin, itraconazole, erythromycin, tolbutamide or clopidogrel indicate that the PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with any of these drugs.","","ncit:negative","ncit:Qualitative","PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with niacin","fluvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","niacin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 18:16:48 -0700","DDI-clinical-trial","evidence-challenges","digoxin (0.375 mg q24h for 8 days). ","Warfarin: Multiple oral doses of Zaleplon (20 mg q24h for 13 days) did not affect the pharmacokinetics of warfarin (R+)- or (S-)-enantiomers or the pharmacodynamics (prothrombin time) following a single 25-mg oral dose of warfarin.","","ncit:negative","ncit:quantitative","did not affect the pharmacokinetics of warfarin","Zaleplon","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","warfarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","25","SD","Oral","1","QD","UNK","13","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/9c4bedb4-2d59-4fcd-aad7-fce988cd96d8.html","2016-02-29 14:22:02 -0700","drug-drug-interaction","evidence-supports","Thioridazine hydrochloride tablet use should be avoided in combination with other drugs that are known to prolong the QTc interval and in patients with congenital long QT syndrome or a history of cardiac arrhythmias. ","Reduced cytochrome P450 2D6 isozyme activity drugs that inhibit this isozyme (e.g., fluoxetine and paroxetine) and certain other drugs (e.g., fluvoxamine, propranolol, and pindolol) appear to appreciably inhibit the metabolism of thioridazine. The resulting elevated levels of thioridazine would be expected to augment the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as Torsades de pointes type arrhythmias.","","ncit:positive","ncit:Qualitative","appear to appreciably inhibit the metabolism of thioridazine and result in elevated levels of thioridazine","propranolol","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"thioridazine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5429f134-839f-4ffc-9944-55f51238def8.html","2015-12-18 13:50:52 -0700","DDI-clinical-trial","evidence-supports","Strong CYP1A2 Inhibitors (e.g., Fluvoxamine ) ","SAPHRIS is metabolized by CYP1A2. Marginal increase of asenapine exposure was observed when SAPHRIS is used with fluvoxamine at 25 mg administered twice daily [see Clinical Pharmacology (12.3)","","ncit:positive","ncit:quantitative","Marginal increase of asenapine exposure","SAPHRIS","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","25","UNK","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c6e131fe-e7df-4876-83f7-9156fc4e8228.html","2016-03-14 15:02:19 -0700","DDI-clinical-trial","evidence-supports"," 7.8 Digoxin ","When multiple doses of LIPITOR and digoxin were co-administered, steady state plasma digoxin concentrations increased by approximately 20%. Patients taking digoxin should be monitored appropriately","","ncit:positive","ncit:quantitative",,"digoxin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","LIPITOR","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","20","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 17:46:48 -0700","DDI-clinical-trial","evidence-challenges","50 mg produced additive effects on decreased alertness and impaired psychomotor performance for 2 to 4 hours after administration. The interaction was pharmacodynamic with no alteration of the pharmacokinetics of either drug. ","Venlafaxine: Coadministration of a single dose of zaleplon 10 mg and multiple doses of venlafaxine ER (extended release) 150 mg did not result in any significant changes in the pharmacokinetics of either zaleplon or venlafaxine. In addition, there was no pharmacodynamic interaction as a result of coadministration of zaleplon and venlafaxine ER.","","ncit:negative","ncit:quantitative","did not result in any significant changes in the pharmacokinetics of either zaleplon or venlafaxine","venlafaxine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","150","zaleplon","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","10","SD","Oral","1","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:09:54 -0800","DDI-clinical-trial","evidence-challenges"," Theophylline ","When nefazodone (200 mg BID) was given to patients being treated with theophylline (600 to 1200 mg/day) for chronic obstructive pulmonary disease, there was no change in the steady-state pharmacokinetics of either nefazodone or theophylline. FEV1 measurements taken when theophylline and nefazodone were coadministered did not differ from baseline dosage (i.e., when theophylline was administered alone). Therefore, dosage adjustment is not necessary for either drug when coadministered.","","ncit:negative","ncit:quantitative",,"theophylline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","600 to 1200","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","Daily","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 13:18:12 -0700","DDI-clinical-trial","evidence-challenges"," — ","Multiple doses of olanzapine (10 mg for 8 days) did not influence the kinetics of lithium. ","","ncit:negative","ncit:quantitative",,"lithium.","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","olanzapine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","10","UNK","Oral","UNK","UNK","Oral","8","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:23:33 -0800","DDI-clinical-trial","evidence-supports"," Cardiovascular-Active Drugs ","Digoxin – When nefazodone (200 mg BID) and digoxin (0.2 mg QD) were coadministered for 9 days to healthy male volunteers (n = 18) who were phenotyped as CYP2D6 extensive metabolizers, Cmax, Cmin, and AUC of digoxin were increased by 29%, 27%, and 15%, respectively.","","ncit:positive","ncit:quantitative",,"nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","digoxin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction",".2","QD","Oral","9","BID","Oral","9","18","15","Percent","Increase","UNK","UNK","UNK","29","Percent","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c6e131fe-e7df-4876-83f7-9156fc4e8228.html","2016-03-14 14:49:42 -0700","drug-drug-interaction","evidence-supports","","Atorvastatin AUC was significantly increased with concomitant administration of LIPITOR with several combinations of HIV protease inhibitors, as well as with the hepatitis C protease inhibitor telaprevir, compared to that of LIPITOR alone [","see ","ncit:positive","ncit:Qualitative","Atorvastatin AUC was significantly increased with concomitant administration","Atorvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","telaprevir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/9c4bedb4-2d59-4fcd-aad7-fce988cd96d8.html","2016-02-29 14:22:02 -0700","drug-drug-interaction","evidence-supports","Thioridazine hydrochloride tablet use should be avoided in combination with other drugs that are known to prolong the QTc interval and in patients with congenital long QT syndrome or a history of cardiac arrhythmias. ","Reduced cytochrome P450 2D6 isozyme activity drugs that inhibit this isozyme (e.g., fluoxetine and paroxetine) and certain other drugs (e.g., fluvoxamine, propranolol, and pindolol) appear to appreciably inhibit the metabolism of thioridazine. The resulting elevated levels of thioridazine would be expected to augment the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as Torsades de pointes type arrhythmias.","","ncit:positive","ncit:Qualitative","appear to appreciably inhibit the metabolism of thioridazine and result in elevated levels of thioridazine","pindolol","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"thioridazine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 21:24:45 -0400","DDI-clinical-trial","evidence-challenges","Drugs That Alter Renal Excretion ","Ibuprofen: Ibuprofen is known to affect renal function and, consequently, alter the renal excretion of other drugs. There was no apparent pharmacokinetic interaction between zaleplon and ibuprofen following single dose administration (10 mg and 600 mg, respectively) of each drug. This was expected because zaleplon is primarily metabolized and renal excretion of unchanged zaleplon accounts for less than 1% of the administered dose. ","","ncit:negative","ncit:quantitative","no apparent pharmacokinetic interaction","zaleplon","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","10","ibuprofen","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","600","SD","Oral","1","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 18:01:31 -0700","DDI-clinical-trial","evidence-supports","","Rifampin: CYP3A4 is ordinarily a minor metabolizing enzyme of zaleplon. Multiple-dose administration of the potent CYP3A4 inducer rifampin (600 mg every 24 hours, q24h, for 14 days), however, reduced zaleplon Cmax and AUC by approximately 80%."," The coadministration of a potent CYP3A4 enzyme inducer, although not posing a safety concern, thus could lead to ineffectiveness of","ncit:positive","ncit:quantitative",,"zaleplon","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","rifampin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","UNK","Oral","UNK","QD","Oral","14","UNK","80","Percent","Decrease","UNK","UNK","UNK","80","Percent","Decrease","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c6e131fe-e7df-4876-83f7-9156fc4e8228.html","2016-03-14 14:46:09 -0700","DDI-clinical-trial","evidence-supports","","Clarithromycin: Atorvastatin AUC was significantly increased with concomitant administration of LIPITOR 80 mg with clarithromycin (500 mg twice daily) compared to that of LIPITOR alone [see Clinical Pharmacology (12.3)]. Therefore, in patients taking clarithromycin, caution should be used when the LIPITOR dose exceeds 20 mg [see Warnings and Precautions, Skeletal Muscle (5.1) and Dosage and Administration (2.6)]. ","","ncit:positive","ncit:quantitative","Atorvastatin AUC was significantly increased with concomitant administration of LIPITOR 80 mg with clarithromycin (500 mg twice daily)","Atorvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","80","clarithromycin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","500","UNK","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 18:26:57 -0500","DDI-clinical-trial","evidence-challenges"," — ","Multiple doses of olanzapine did not affect the pharmacokinetics of theophylline or its metabolites. ","","ncit:negative","ncit:quantitative",,"theophylline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","olanzapine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c6e131fe-e7df-4876-83f7-9156fc4e8228.html","2016-03-14 14:54:30 -0700","DDI-clinical-trial","evidence-supports","","Itraconazole: Atorvastatin AUC was significantly increased with concomitant administration of LIPITOR 40 mg and itraconazole 200 mg [see Clinical Pharmacology (12.3)]. Therefore, in patients taking itraconazole, caution should be used when the LIPITOR dose exceeds 20 mg [see Warnings and Precautions, Skeletal Muscle (5.1) and Dosage and Administration (2.6)]. ","","ncit:positive","ncit:quantitative","Atorvastatin AUC was significantly increased with concomitant administration of LIPITOR 40 mg and itraconazole 200 mg","itraconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","Atorvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","40","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 11:02:59 -0700","drug-drug-interaction","evidence-challenges","did not meaningfully alter the pharmacokinetics of apixaban . ","In studies conducted in healthy subjects, apixaban did not meaningfully alter the pharmacokinetics of digoxin, naproxen, atenolol, prasugrel, or acetylsalicylic acid.","","ncit:negative","ncit:Qualitative","pixaban did not meaningfully alter the pharmacokinetics of naproxen","apixaban","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"naproxen","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 14:04:43 -0400","drug-drug-interaction","evidence-challenges","did not meaningfully alter the pharmacokinetics of apixaban . ","In studies conducted in healthy subjects, apixaban did not meaningfully alter the pharmacokinetics of digoxin, naproxen, atenolol, prasugrel, or acetylsalicylic acid.","","ncit:negative","ncit:Qualitative","pixaban did not meaningfully alter the pharmacokinetics of atenolol","atenolol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","apixaban","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:47:05 -0800","DDI-clinical-trial","evidence-challenges","are coadministered; plasma level monitoring for digoxin is recommended. ","Propranolol – The coadministration of nefazodone (200 mg BID) and propranolol (40 mg BID) for 5.5 days to healthy male volunteers (n = 18), including 3 poor and 15 extensive CYP2D6 metabolizers, resulted in 30% and 14% reductions in Cmax and AUC of propranolol, respectively, and a 14% reduction in Cmax for the metabolite, 4-hydroxypropranolol. The kinetics of nefazodone, hydroxynefazodone, and triazole-dione were not affected by coadministration of propranolol. However, Cmax, Cmin, and AUC of m-chlorophenylpiperazine were increased by 23%, 54%, and 28%, respectively. No change in initial dose of either drug is necessary and dose adjustments should be made on the basis of clinical response.","","ncit:negative","ncit:quantitative",,"propranolol","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","nefazodone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","200","BID","Oral","5.5","BID","Oral","5.5","18","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 12:08:12 -0800","DDI-clinical-trial","evidence-challenges","were increased by 23%, 54%, and 28%, respectively. No change in initial dose of either drug is necessary and dose adjustments should be made on the basis of clinical response. ","HMG-CoA Reductase Inhibitors – When single 40 mg doses of simvastatin or atorvastatin, both substrates of CYP3A4, were given to healthy adult volunteers who had received nefazodone hydrochloride, 200 mg BID for 6 days, approximately 20 fold increases in plasma concentrations of simvastatin and simvastatin acid and 3 to 4 fold increases in plasma concentrations of atorvastatin and atorvastatin lactone were seen. These effects appear to be due to the inhibition of CYP3A4 by nefazodone because, in the same study, nefazodone had no significant effect on the plasma concentrations of pravastatin, which is not metabolized by CYP3A4 to a clinically significant extent","","ncit:negative","ncit:quantitative",,"pravastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","UNK","Oral","UNK","BID","Oral","6","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/7b8e5b26-b9e4-4704-921b-3c3c0d159916.html","2015-11-29 16:15:29 -0700","drug-drug-interaction","evidence-challenges",". ","In a clinical study, subjects on stable doses of valproate had comparable valproate average plasma concentrations when INVEGA® 3–15 mg/day was added to their existing valproate treatment.","","ncit:negative","ncit:Qualitative","omparable valproate average plasma concentrations","INVEGA","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"valproate","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:53:19 -0700","drug-drug-interaction","evidence-challenges","Other Drugs with No Interactions with Zolpidem ","A study involving cimetidine/zolpidem tartrate and ranitidine/zolpidem tartrate combinations revealed no effect of either drug on the pharmacokinetics or pharmacodynamics of zolpidem.","","ncit:negative","ncit:Qualitative","no effect of either drug on the pharmacokinetics or pharmacodynamics of zolpidem.","zolpidem","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a971ea18-40cf-4a01-b696-180ccc3fddb5.html","2016-02-29 16:08:19 -0500","drug-drug-interaction","evidence-supports","Antihypertensive effects of guanethidine and related compounds may be counteracted when phenothiazines are used concomitantly. ","Concomitant administration of propranolol with phenothiazines results in increased plasma levels of both drugs","","ncit:positive","ncit:Qualitative","results in increased plasma levels of both drugs","phenothiazines","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"propranolol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ee49f3b1-1650-47ff-9fb1-ea53fe0b92b6.html","2016-03-14 13:55:11 -0700","DDI-clinical-trial","evidence-supports","aripiprazole pharmacokinetics ","The effects of ABILIFY on the exposures of other drugs are summarized in Figure 21. A population PK analysis in patients with major depressive disorder showed no substantial change in plasma concentrations of fluoxetine (20 mg/day or 40 mg/day), paroxetine CR (37.5 mg/day or 50 mg/day), or sertraline (100 mg/day or 150 mg/day) dosed to steady-state. The steady-state plasma concentrations of fluoxetine and norfluoxetine increased by about 18% and 36%, respectively, and concentrations of paroxetine decreased by about 27%. The steady-state plasma concentrations of sertraline and desmethylsertraline were not substantially changed when these antidepressant therapies were coadministered with aripiprazole.","","ncit:positive","ncit:quantitative","this was a pop pk study","paroxetine CR","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","37.5-50","ABILIFY","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","Daily","Oral","UNK","UNK","Oral","UNK","UNK","27","Percent","Decrease","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:45:30 -0700","DDI-clinical-trial","evidence-supports","20 mg at steady-state levels in male volunteers did not demonstrate any clinically significant pharmacokinetic or pharmacodynamic interactions. ","When multiple doses of zolpidem and fluoxetine were given at steady state and the concentrations evaluated in healthy females, an increase in the zolpidem half-life (17%) was observed. There was no evidence of an additive effect in psychomotor performance.","","ncit:positive","ncit:quantitative","in healthy females","fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","zolpidem","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","UNK","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","17","Percent","Increase" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:53:39 -0700","drug-drug-interaction","evidence-challenges","Other Drugs with No Interactions with Zolpidem ","A study involving cimetidine/zolpidem tartrate and ranitidine/zolpidem tartrate combinations revealed no effect of either drug on the pharmacokinetics or pharmacodynamics of zolpidem.","","ncit:negative","ncit:Qualitative","no effect of either drug on the pharmacokinetics or pharmacodynamics of zolpidem.","zolpidem","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","ranitidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/fdbfe194-b845-42c5-bb87-a48118bc72e7.html","2016-03-31 12:23:25 -0700","drug-drug-interaction","evidence-supports","is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. ","Elevated plasma levels of HMG-CoA reductase inhibitory activity increases the risk of myopathy and rhabdomyolysis, particularly with higher doses of simvastatin. [See Warnings and Precautions (5.1) and Clinical Pharmacology (12.3).] Concomitant use of drugs labeled as having a strong inhibitory effect on CYP3A4 is contraindicated [see Contraindications (4)]. If treatment with itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with simvastatin must be suspended during the course of treatment.","","ncit:positive","ncit:Qualitative","strong inhibitor of CYP3A4 may elevate simvastatin plasma level","simvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","erythromycin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/fdbfe194-b845-42c5-bb87-a48118bc72e7.html","2016-03-31 12:38:39 -0700","drug-drug-interaction","evidence-supports","is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. ","Elevated plasma levels of HMG-CoA reductase inhibitory activity increases the risk of myopathy and rhabdomyolysis, particularly with higher doses of simvastatin. [See Warnings and Precautions (5.1) and Clinical Pharmacology (12.3).] Concomitant use of drugs labeled as having a strong inhibitory effect on CYP3A4 is contraindicated [see Contraindications (4)]. If treatment with itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with simvastatin must be suspended during the course of treatment.","","ncit:positive","ncit:Qualitative","strong inhibitor of CYP3A4 may elevate simvastatin plasma level","telithromycin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"simvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/44dcbf97-99ec-427c-ba50-207e0069d6d2.html","2016-03-31 13:20:20 -0400","drug-drug-interaction","evidence-challenges"," 7.8 Warfarin ","LIVALO had no significant pharmacokinetic interaction with R- and S- warfarin. LIVALO had no significant effect on prothrombin time (PT) and international normalized ratio (INR) when administered to patients receiving chronic warfarin treatment [see Clinical Pharmacology (12.3)]. However, patients receiving warfarin should have their PT and INR monitored when pitavastatin is added to their therapy. ","","ncit:negative","ncit:Qualitative","Pitavastatin had no significant pharmacokinetic interaction with R- and S- warfarin. and no significant effect on prothrombin time (PT) and international normalized ratio (INR) when administered to patients receiving chronic warfarin.Study details in section 12 Table 3","pitavastatin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"warfarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 17:37:17 -0700","DDI-clinical-trial","evidence-challenges",", reflecting the absence of a role of CYP2D6 in zaleplon 's metabolism. ","Thioridazine: Coadministration of single doses of Zaleplon 20 mg and thioridazine 50 mg produced additive effects on decreased alertness and impaired psychomotor performance for 2 to 4 hours after administration. The interaction was pharmacodynamic with no alteration of the pharmacokinetics of either drug.","","ncit:negative","ncit:quantitative","no alteration of the pharmacokinetics of either drug.","Zaleplon","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","thioridazine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","50","SD","UNK","1","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:37:36 -0800","DDI-clinical-trial","evidence-challenges"," Cardiovascular-Active Drugs ","Digoxin – When nefazodone (200 mg BID) and digoxin (0.2 mg QD) were coadministered for 9 days to healthy male volunteers (n = 18) who were phenotyped as CYP2D6 extensive metabolizers, Cmax, Cmin, and AUC of digoxin were increased by 29%, 27%, and 15%, respectively. Digoxin had no effects on the pharmacokinetics of nefazodone and its active metabolites. Because of the narrow therapeutic index of digoxin, caution should be exercised when nefazodone and digoxin are coadministered; plasma level monitoring for digoxin is recommended.","","ncit:negative","ncit:quantitative",,"digoxin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",".2","nefazodone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","200","BID","Oral","9","QD","Oral","9","18","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/39a5dae2-49f7-4662-9eac-aa7b4c7807a4.html","2016-05-09 16:27:24 -0700","drug-drug-interaction","evidence-challenges","."," When eszopiclone was coadministered with olanzapine, no pharmacokinetic interaction was detected in levels of eszopiclone or olanzapine, but a pharmacodynamic interaction was seen on a measure of psychomotor function.","","ncit:negative","ncit:Qualitative","eszopiclone was coadministered with olanzapine, no pharmacokinetic interaction was detected in levels of eszopiclone or olanzapine","olanzapine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"eszopiclone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 10:50:04 -0700","drug-drug-interaction","evidence-supports","7.2 Strong Dual Inducers of CYP3A4 and P-gp ","Avoid concomitant use of ELIQUIS with strong dual inducers of CYP3A4 and P-gp (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort) because such drugs will decrease exposure to apixaban [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative","phenytoin will decrease exposure to apixaban","phenytoin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"apixaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/fdbfe194-b845-42c5-bb87-a48118bc72e7.html","2016-03-31 12:22:09 -0700","drug-drug-interaction","evidence-supports","is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. ","Elevated plasma levels of HMG-CoA reductase inhibitory activity increases the risk of myopathy and rhabdomyolysis, particularly with higher doses of simvastatin. [See Warnings and Precautions (5.1) and Clinical Pharmacology (12.3).] Concomitant use of drugs labeled as having a strong inhibitory effect on CYP3A4 is contraindicated [see Contraindications (4)]. If treatment with itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with simvastatin must be suspended during the course of treatment.","","ncit:positive","ncit:Qualitative","strong inhibitor of CYP3A4 may elevate simvastatin plasma level","simvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","itraconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/7b8e5b26-b9e4-4704-921b-3c3c0d159916.html","2015-11-29 18:21:18 -0500","DDI-clinical-trial","evidence-supports","have not been studied. The clinical relevance is unknown. ","Co-administration of a single dose of INVEGA® 12 mg with divalproex sodium extended-release tablets (two 500 mg tablets once daily) resulted in an increase of approximately 50% in the Cmax and AUC of paliperidone. Dosage reduction for INVEGA® should be considered when INVEGA® is co-administered with valproate after clinical assessment.","","ncit:positive","ncit:quantitative",,"INVEGA","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","12","divalproex sodium","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","1000","SD","Oral","1","QD","Oral","UNK","UNK","50","Percent","Increase","UNK","UNK","UNK","50","Percent","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:26:31 -0700","drug-drug-interaction","evidence-supports","7.1 Drugs that Inhibit Cytochrome P450 3A4 Enzymes and Drug Transport Systems ","In drug interaction studies evaluating the concomitant use with drugs that are combined P-gp and CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin, erythromycin and fluconazole), increases in rivaroxaban exposure and pharmacodynamic effects (i.e., factor Xa inhibition and PT prolongation) were observed. The increases in exposure ranged from 30% to 160%. Significant increases in rivaroxaban exposure may increase bleeding risk [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative","increases in rivaroxaban exposure","erythromycin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"rivaroxaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c6e131fe-e7df-4876-83f7-9156fc4e8228.html","2016-03-14 15:04:06 -0700","drug-drug-interaction","evidence-supports"," 7.9 Oral Contraceptives ","Co-administration of LIPITOR and an oral contraceptive increased AUC values for norethindrone and ethinyl estradiol [see Clinical Pharmacology (12.3)]. These increases should be considered when selecting an oral contraceptive for a woman taking LIPITOR.","","ncit:positive","ncit:Qualitative","Co-administration of LIPITOR and an oral contraceptive increased AUC values for norethindrone and ethinyl estradiol","norethindrone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","LIPITOR","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/afad3051-9df2-4c54-9684-e8262a133af8.html","2015-12-08 19:34:38 -0700","DDI-clinical-trial","evidence-challenges","","Valproate: It is not necessary to adjust the LATUDA dose when used concomitantly with valproate. A dedicated drug-drug interaction study has not been conducted with valproate and LATUDA. Based on pharmacokinetic data from the bipolar depression studies valproate levels were not affected by lurasidone, and lurasidone concentrations were not affected by valproate. ","","ncit:negative","ncit:quantitative",,"lurasidone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","valproate","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 18:04:06 -0700","DDI-clinical-trial","evidence-supports"," dose. ","Coadministration of single, oral doses of zaleplon with erythromycin (10 mg and 800 mg, respectively), a strong, selective CYP3A4 inhibitor, produced a 34% increase in zaleplon's maximal plasma concentrations and a 20% increase in the area under the plasma concentration-time curve. ","The magnitude of interaction with multiple doses of","ncit:positive","ncit:quantitative",,"zaleplon","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","10","erythromycin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","80","SD","Oral","1","SD","Oral","1","UNK","20","Percent","Increase","UNK","UNK","UNK","34","Percent","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:39:55 -0700","drug-drug-interaction","evidence-supports","CYP2D6 and CYP3A4 Inhibitors ","Concomitant treatment with CLOZARIL and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology (12.3)]. Use caution and monitor patients closely when using such inhibitors. Consider reducing the CLOZARIL dose [see Dosage and Administration (2.6)].","","ncit:positive","ncit:Qualitative","escitalopram can increase clozapine levels","escitalopram","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"clozapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:41:56 -0700","drug-drug-interaction","evidence-supports","CYP2D6 and CYP3A4 Inhibitors ","Concomitant treatment with CLOZARIL and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology (12.3)]. Use caution and monitor patients closely when using such inhibitors. Consider reducing the CLOZARIL dose [see Dosage and Administration (2.6)]","","ncit:positive","ncit:Qualitative","Quinidine can increase clozapine levels","quinidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"clozapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:07:13 -0800","DDI-clinical-trial","evidence-challenges"," Cimetidine ","When nefazodone (200 mg BID) and cimetidine (300 mg QID) were coadministered for one week, no change in the steady-state pharmacokinetics of either nefazodone or cimetidine was observed compared to each dosed alone. Therefore, dosage adjustment is not necessary for either drug when coadministered.","","ncit:negative","ncit:quantitative",,"nefazodone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","200","cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","300","BID","Oral","7","QID","Oral","7","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d78e9639-6fab-4a78-8b29-6991a18ae6c6.html","2016-02-19 17:46:51 -0500","drug-drug-interaction","evidence-supports","ity of this enzyme, so-called “poor” metabolizers. Among other populations the prevalence is not known. Poor metabolizers demonstrate higher plasma concentrations of antipsychotic drugs at usual doses, which may correlate with emergence of side effects. ","In one study of 45 elderly patients suffering from dementia treated with perphenazine, the 5 patients who were prospectively identified as poor P450 2D6 metabolizers had reported significantly greater side effects during the first 10 days of treatment than the 40 extensive metabolizers, following which the groups tended to converge. Prospective phenotyping of elderly patients prior to antipsychotic treatment may identify those at risk for adverse events. The concomitant administration of other drugs that inhibit the activity of P450 2D6 may acutely increase plasma concentrations of antipsychotics. Among these are tricyclic antidepressants and selective serotonin reuptake inhibitors, e.g., fluoxetine, sertraline and paroxetine. When prescribing these drugs to patients already receiving antipsychotic therapy, close monitoring is essential and dose reduction may become necessary to avoid toxicity. Lower doses than usually prescribed for either the antipsychotic or the other drug may be required.","","ncit:positive","ncit:Qualitative","may acutely increase plasma concentrations of antipsychotics.","fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"perphenazine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/9c4bedb4-2d59-4fcd-aad7-fce988cd96d8.html","2016-02-29 14:37:32 -0700","DDI-clinical-trial","evidence-supports"," Fluvoxamine ","The effect of fluvoxamine (25 mg b.i.d. for one week) on thioridazine steady-state concentration was evaluated in ten male inpatients with schizophrenia. Concentrations of thioridazine and its two active metabolites, mesoridazine and sulforidazine, increased 3-fold following coadministration of fluvoxamine. Fluvoxamine and thioridazine should not be coadministered.","","ncit:positive","ncit:quantitative",,"mesoridazine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","25","Fluvoxamine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","BID","Oral","7","10","3","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 17:50:18 -0700","DDI-clinical-trial","evidence-challenges","50 mg produced additive effects on decreased alertness and impaired psychomotor performance for 2 to 4 hours after administration. The interaction was pharmacodynamic with no alteration of the pharmacokinetics of either drug. ","Venlafaxine: Coadministration of a single dose of zaleplon 10 mg and multiple doses of venlafaxine ER (extended release) 150 mg did not result in any significant changes in the pharmacokinetics of either zaleplon or venlafaxine. In addition, there was no pharmacodynamic interaction as a result of coadministration of zaleplon and venlafaxine ER.","","ncit:negative","ncit:quantitative","did not result in any significant changes in the pharmacokinetics of either zaleplon or venlafaxine","zaleplon","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","10","venlafaxine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","150","UNK","Oral","UNK","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c6e131fe-e7df-4876-83f7-9156fc4e8228.html","2016-03-14 15:25:58 -0700","DDI-clinical-trial","evidence-supports","TABLE 3. Effect of Co-administered Drugs on the Pharmacokinetics of Atorvastatin ","Co-administered drug and dosing regimen Atorvastatin Dose (mg) Change in AUC* Change in Cmax* * Data given as x-fold change represent a simple ratio between co-administration and atorvastatin alone (i.e., 1-fold = no change). Data given as % change represent % difference relative to atorvastatin alone (i.e., 0% = no change). † See Sections 5.1 and 7 for clinical significance. ‡ The dose of saquinavir plus ritonavir in this study is not the clinically used dose. The increase in atorvastatin exposure when used clinically is likely to be higher than what was observed in this study. Therefore, caution should be applied and the lowest dose necessary should be used. § Greater increases in AUC (up to 2.5 fold) and/or Cmax (up to 71%) have been reported with excessive grapefruit consumption (≥ 750 mL – 1.2 liters per day). ¶ Single sample taken 8–16 h post dose. # Due to the dual interaction mechanism of rifampin, simultaneous co-administration of atorvastatin with rifampin is recommended, as delayed administration of atorvastatin after administration of rifampin has been associated with a significant reduction in atorvastatin plasma concentrations. †Cyclosporine 5.2 mg/kg/day, stable dose 10 mg QD for 28 days ↑ 8.7 fold ↑ 10.7 fold","","ncit:positive","ncit:quantitative","Table 3","atorvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","10","Cyclosporine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","5.2mg/kg/day","QD","Oral","28","Daily","Oral","UNK","UNK","8.7","Fold","Increase","UNK","UNK","UNK","10.7","Fold","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 15:52:59 -0700","DDI-clinical-trial","evidence-supports","","When coadministered with a loading dose of 180 mg ticagrelor, the AUCτ,ss and Cmax,ss of dabigatran increased by 49% and 65%, respectively","; but when","ncit:positive","ncit:quantitative",,"ticagrelor","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","180","dabigatran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","SD","Oral","1","UNK","49","Percent","Increase","UNK","UNK","UNK","65","UNK","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 17:48:17 -0700","DDI-clinical-trial","evidence-challenges","","In addition, there were no significant pharmacokinetic interactions observed in studies comparing concomitant rivaroxaban 20 mg and 7.5 mg single dose of midazolam ","(substrate of CYP3A4), 0.375 mg once-daily dose of","ncit:negative","ncit:quantitative","no significant pharmacokinetic interactions observed","midazolam","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","7.5","rivaroxaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","20","UNK","Oral","UNK","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c6e131fe-e7df-4876-83f7-9156fc4e8228.html","2016-03-30 18:03:19 -0400","drug-drug-interaction","evidence-challenges"," 7.10 Warfarin ","LIPITOR had no clinically significant effect on prothrombin time when administered to patients receiving chronic warfarin treatment.","","ncit:negative","ncit:Qualitative","Concomitant Lipitor and warfarin had no clinically significant effect on prothrombin time","warfarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","LIPITOR","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2015-11-29 15:19:40 -0700","DDI-clinical-trial","evidence-challenges","F","luoxetine: A single 3 mg dose of iloperidone had no effect on the pharmacokinetics of fluoxetine (20 mg twice daily). ","","ncit:negative","ncit:quantitative",,"fluoxetine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","20","iloperidone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","3","BID","Oral","UNK","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:51:51 -0700","DDI-clinical-trial","evidence-supports",", a CYP3A4 inducer, significantly reduced the exposure to and the pharmacodynamic effects of zolpidem . ","A single-dose interaction study with zolpidem tartrate 5 mg and ketoconazole, a potent CYP3A4 inhibitor, given as 200 mg twice daily for 2 days increased Cmax of zolpidem (30%) and the total AUC of zolpidem (70%) compared to zolpidem alone and prolonged the elimination half-life (30 %) along with an increase in the pharmacodynamic effects of zolpidem. Consideration should be given to using a lower dose of zolpidem when ketoconazole and zolpidem are given together.","","ncit:positive","ncit:quantitative",,"ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","zolpidem","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","5","SD","Oral","1","BID","Oral","2","UNK","70","UNK","Increase","UNK","UNK","UNK","30","Percent","Increase","30","Percent","Increase" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 13:12:47 -0800","DDI-clinical-trial","evidence-challenges","","Nefazodone plasma concentrations were unaffected by alprazolam. ","If","ncit:negative","ncit:quantitative",,"Nefazodone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","200","alprazolam","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","1","BID","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:39:52 -0700","DDI-clinical-trial","evidence-supports","increased by 160% and 70%, respectively. Similar increases in pharmacodynamic effects were also observed. ","Ritonavir (combined P-gp and strong CYP3A4 inhibitor): Single-dose rivaroxaban AUC and Cmax increased by 150% and 60%, respectively. Similar increases in pharmacodynamic effects were also observed.","","ncit:positive","ncit:quantitative",,"rivaroxaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","Ritonavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","150","Percent","Increase","UNK","UNK","UNK","60","UNK","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/39a5dae2-49f7-4662-9eac-aa7b4c7807a4.html","2016-05-09 16:27:24 -0700","drug-drug-interaction","evidence-supports","","CYP3A4 is a major metabolic pathway for elimination of eszopiclone. The exposure of eszopiclone was increased by coadministration of ketoconazole, a potent inhibitor of CYP3A4. ","Other strong inhibitors of CYP3A4 (e.g.,","ncit:positive","ncit:Qualitative","exposure of eszopiclone was increased by coadministration of ketoconazole","eszopiclone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 14:24:30 -0800","DDI-clinical-trial","evidence-challenges"," –"," When fluoxetine (20 mg QD) and nefazodone (200 mg BID) were administered at steady state there were no changes in the pharmacokinetic parameters for fluoxetine or its metabolite, norfluoxetine.","","ncit:negative","ncit:quantitative",,"nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","norfluoxetine","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","20","QD","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 10:40:46 -0800","DDI-clinical-trial","evidence-challenges","dosage should be guided by usual clinical practices. ","Desipramine – When nefazodone (150 mg BID) and desipramine (75 mg QD) were administered together there were no changes in the pharmacokinetics of desipramine or its metabolite, 2-hydroxy desipramine. ","","ncit:negative","ncit:quantitative",,"2-hydroxy desipramine.","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","75","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","150","QD","Oral","UNK","BID","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 16:15:52 -0700","drug-drug-interaction","evidence-supports","is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. ","Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin. (See CONTRAINDICATIONS, WARNINGS, Myopathy/Rhabdomyolysis, and CLINICAL PHARMACOLOGY, Pharmacokinetics.)","","ncit:positive","ncit:Qualitative","Teleprevir is a strong inhibitor of CYP3A4 and reduces the elimination of lovastatin","lovastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","telaprevir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/9c4bedb4-2d59-4fcd-aad7-fce988cd96d8.html","2016-02-29 16:44:38 -0500","drug-drug-interaction","evidence-supports"," Pindolol ","Concurrent administration of pindolol and thioridazine have resulted in moderate, dose related increases in the serum levels of thioridazine and two of its metabolites, as well as higher than expected serum pindolol levels. Pindolol and thioridazine should not be coadministered.","","ncit:positive","ncit:Qualitative","dose related increases in the serum levels of thioridazine and two of its metabolites,","pindolol","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"thioridazine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a4ee3907-45d4-41b9-af8a-39a9966cd533.html","2016-05-10 13:18:17 -0400","drug-drug-interaction","evidence-challenges"," Drug Interactions ","The pharmacokinetic profile of temazepam does not appear to be altered by orally administered cimetidine dosed according to labeling.","","ncit:negative","ncit:Qualitative","harmacokinetic profile of temazepam does not appear to be altered by orally administered cimetidine","cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"temazepam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-12 10:33:55 -0700","DDI-clinical-trial","evidence-challenges",": "," Enoxaparin 40 mg given subcutaneously for 3 days with the last dose given 24 hours before a single dose of PRADAXA had no impact on the exposure to dabigatran or the coagulation measures aPTT, ECT, or TT","","ncit:negative","ncit:quantitative","enoxaparin had no impact on the exposure to dabigatran","dabigatran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","Enoxaparin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","SD","Oral","1","UNK","UNK","3","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 14:07:38 -0800","DDI-clinical-trial","evidence-supports","metabolite 1-pyrimidinylpiperazine. ","With 5 mg BID doses of buspirone, slight increases in AUC were observed for nefazodone (23%) and its metabolites hydroxynefazodone (17%) and mCPP (9%)","","ncit:positive","ncit:quantitative",,"hydroxynefazodone","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","250","buspirone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","5","BID","Oral","UNK","BID","Oral","UNK","UNK","17","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 12:46:01 -0700","drug-drug-interaction","evidence-supports"," —"," Omeprazole and rifampin may cause an increase in olanzapine clearance. ","","ncit:positive","ncit:Qualitative","may cause an increase in olanzapine clearance.","olanzapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Omeprazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 12:00:53 -0800","DDI-clinical-trial","evidence-supports","were increased by 23%, 54%, and 28%, respectively. No change in initial dose of either drug is necessary and dose adjustments should be made on the basis of clinical response. ","HMG-CoA Reductase Inhibitors – When single 40 mg doses of simvastatin or atorvastatin, both substrates of CYP3A4, were given to healthy adult volunteers who had received nefazodone hydrochloride, 200 mg BID for 6 days, approximately 20 fold increases in plasma concentrations of simvastatin and simvastatin acid and 3 to 4 fold increases in plasma concentrations of atorvastatin and atorvastatin lactone were seen. These effects appear to be due to the inhibition of CYP3A4 by nefazodone because, in the same study, nefazodone had no significant effect on the plasma concentrations of pravastatin, which is not metabolized by CYP3A4 to a clinically significant extent.","","ncit:positive","ncit:quantitative","entered plasma concentration increase as AUC","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","simvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","40","QD","Oral","1","BID","Oral","6","UNK","20","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-27 14:35:40 -0800","DDI-clinical-trial","evidence-supports","in ‘Poor Metabolizers’ and Potential Interaction With Drugs That Inhibit and/or Are Metabolized by Cytochrome P450 Isozymes. Fluoxetine – ","When fluoxetine (20 mg QD) and nefazodone (200 mg BID) were administered at steady state there were no changes in the pharmacokinetic parameters for fluoxetine or its metabolite, norfluoxetine. Similarly, there were no changes in the pharmacokinetic parameters of nefazodone or HO-NEF; however, the mean AUC levels of the nefazodone metabolites mCPP and triazole-dione increased by 3 to 6 fold and 1.3 fold, respectively","","ncit:positive","ncit:quantitative",,"triazole-dione","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","200","fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","BID","Oral","UNK","QD","Oral","UNK","UNK","1.3","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e1e5249-1cb7-4cc2-ad5a-cdeeee2f494f.html","2016-02-16 16:33:50 -0700","drug-drug-interaction","evidence-supports","","Quetiapine exposure is increased by the prototype CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.)",". and decreased by the prototype CYP3A4 inducers (e..g,","ncit:positive","ncit:Qualitative","quetiapine exposure is increased by CYP3A4 inhibitors","Quetiapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:41:53 -0800","DDI-clinical-trial","evidence-supports","are coadministered; plasma level monitoring for digoxin is recommended. ","Propranolol – The coadministration of nefazodone (200 mg BID) and propranolol (40 mg BID) for 5.5 days to healthy male volunteers (n = 18), including 3 poor and 15 extensive CYP2D6 metabolizers, resulted in 30% and 14% reductions in Cmax and AUC of propranolol, respectively, and a 14% reduction in Cmax for the metabolite, 4-hydroxypropranolol.","","ncit:positive","ncit:quantitative",,"4-hydroxypropranolol","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","40","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","BID","Oral","5.5","BID","Oral","5.5","18","UNK","UNK","UNK","UNK","UNK","UNK","14","Percent","Decrease","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-31 12:59:55 -0700","drug-drug-interaction","evidence-challenges","fluvastatin sodium extended-release tablets, 80 mg QD for 19 days ↓2% ↑27% ","Data from drug-drug interaction studies involving fluvastatin and coadministration of either gemfibrozil, tolbutamide or losartan indicate that the PK disposition of either gemfibrozil, tolbutamide or losartan is not significantly altered when coadministered with fluvastatin","","ncit:negative","ncit:Qualitative","PK disposition of tolbutamide is not significantly altered when coadministered with fluvastatin.","fluvastatin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"tolbutamide","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ee49f3b1-1650-47ff-9fb1-ea53fe0b92b6.html","2016-03-14 13:48:36 -0700","DDI-clinical-trial","evidence-supports","aripiprazole pharmacokinetics ","The effects of ABILIFY on the exposures of other drugs are summarized in Figure 21. A population PK analysis in patients with major depressive disorder showed no substantial change in plasma concentrations of fluoxetine (20 mg/day or 40 mg/day), paroxetine CR (37.5 mg/day or 50 mg/day), or sertraline (100 mg/day or 150 mg/day) dosed to steady-state. The steady-state plasma concentrations of fluoxetine and norfluoxetine increased by about 18% and 36%, respectively, and concentrations of paroxetine decreased by about 27%. The steady-state plasma concentrations of sertraline and desmethylsertraline were not substantially changed when these antidepressant therapies were coadministered with aripiprazole.","","ncit:positive","ncit:quantitative","this was a pop pk study","ABILIFY","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","fluoxetine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","20-40","Daily","Oral","UNK","UNK","Oral","UNK","UNK","18","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:49:24 -0700","DDI-clinical-trial","evidence-supports","detected on subjective drowsiness, postural sway, or psychomotor performance. ","A single-dose interaction study with zolpidem tartrate 10 mg and rifampin 600 mg at steady-state levels in female subjects showed significant reductions of the AUC (-73%), Cmax (-58%), and T1/2 (-36 %) of zolpidem together with significant reductions in the pharmacodynamic effects of zolpidem tartrate. Rifampin, a CYP3A4 inducer, significantly reduced the exposure to and the pharmacodynamic effects of zolpidem.","","ncit:positive","ncit:quantitative",,"rifampin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","zolpidem","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","10","SD","Oral","1","UNK","Oral","UNK","UNK","73","Percent","Decrease","UNK","UNK","UNK","58","Percent","Decrease","36","Percent","Increase" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 10:47:19 -0800","DDI-clinical-trial","evidence-supports","or its metabolite, 2-hydroxy desipramine . ","There were also no changes in the pharmacokinetics of nefazodone or its triazole-dione metabolite, but the AUC and Cmax of mCPP increased by 44% and 48%, respectively, while the AUC of HO-NEF decreased by 19%. No changes in doses of either nefazodone or desipramine are necessary when the two drugs are given concomitantly. Subsequent dose adjustments should be made on the basis of clinical response.","","ncit:positive","ncit:quantitative",,"HO-NEF","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","150","desipramine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","75","BID","Oral","UNK","QD","Oral","UNK","UNK","19","Percent","Decrease","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/49c4105b-e518-481c-a248-6684135f5bc1.html","2015-11-29 16:36:20 -0700","DDI-clinical-trial","evidence-supports","is not recommended. Valproate ","Repeated oral doses of risperidone (4 mg once daily) did not affect the pre-dose or average plasma concentrations and exposure (AUC) of valproate (1000 mg/day in three divided doses) compared to placebo (n=21). However, there was a 20% increase in valproate peak plasma concentration (Cmax) after concomitant administration of risperidone. Dose adjustment for valproate is not recommended.","","ncit:positive","ncit:quantitative",,"risperidone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","4","valproate","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","1000","Daily","Oral","UNK","QD","Oral","UNK","21","UNK","UNK","UNK","UNK","UNK","UNK","20","Percent","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/fdbfe194-b845-42c5-bb87-a48118bc72e7.html","2016-03-31 12:22:09 -0700","drug-drug-interaction","evidence-supports","is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. ","Elevated plasma levels of HMG-CoA reductase inhibitory activity increases the risk of myopathy and rhabdomyolysis, particularly with higher doses of simvastatin. [See Warnings and Precautions (5.1) and Clinical Pharmacology (12.3).] Concomitant use of drugs labeled as having a strong inhibitory effect on CYP3A4 is contraindicated [see Contraindications (4)]. If treatment with itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with simvastatin must be suspended during the course of treatment.","","ncit:positive","ncit:Qualitative","strong inhibitor of CYP3A4 may elevate simvastatin plasma level","ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"simvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 16:25:17 -0700","DDI-clinical-trial","evidence-challenges"," — ","Multiple doses of olanzapine did not influence the kinetics of biperiden. ","","ncit:negative","ncit:quantitative",,"olanzapine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","biperiden","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/9c4bedb4-2d59-4fcd-aad7-fce988cd96d8.html","2016-02-29 14:34:13 -0700","DDI-clinical-trial","evidence-supports"," Fluvoxamine ","The effect of fluvoxamine (25 mg b.i.d. for one week) on thioridazine steady-state concentration was evaluated in ten male inpatients with schizophrenia. Concentrations of thioridazine and its two active metabolites, mesoridazine and sulforidazine, increased 3-fold following coadministration of fluvoxamine. Fluvoxamine and thioridazine should not be coadministered.","","ncit:positive","ncit:quantitative",,"thioridazine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","Fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","25","UNK","Oral","UNK","BID","Oral","7","10","3","Fold","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c6e131fe-e7df-4876-83f7-9156fc4e8228.html","2016-03-14 14:57:35 -0700","DDI-clinical-trial","evidence-supports","","Atorvastatin and atorvastatin-metabolites are substrates of the OATP1B1 transporter. Inhibitors of the OATP1B1 (e.g., cyclosporine) can increase the bioavailability of atorvastatin. Atorvastatin AUC was significantly increased with concomitant administration of LIPITOR 10 mg and cyclosporine 5.2 mg/kg/day compared to that of LIPITOR alone [see Clinical Pharmacology (12.3)]. The co-administration of LIPITOR with cyclosporine should be avoided ","[see","ncit:positive","ncit:quantitative","Atorvastatin AUC was significantly increased with concomitant administration of LIPITOR 10 mg and cyclosporine 5.2 mg/kg/day compared to that of LIPITOR alone","atorvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","10","cyclosporine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","5.2 mg/kg/day","UNK","Oral","UNK","Daily","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:26:31 -0700","drug-drug-interaction","evidence-supports","7.1 Drugs that Inhibit Cytochrome P450 3A4 Enzymes and Drug Transport Systems ","In drug interaction studies evaluating the concomitant use with drugs that are combined P-gp and CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin, erythromycin and fluconazole), increases in rivaroxaban exposure and pharmacodynamic effects (i.e., factor Xa inhibition and PT prolongation) were observed. The increases in exposure ranged from 30% to 160%. Significant increases in rivaroxaban exposure may increase bleeding risk [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative","increases in rivaroxaban exposure","rivaroxaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","clarithromycin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 17:35:54 -0700","drug-drug-interaction","evidence-challenges","."," In a single-dose drug interaction study there were no pharmacokinetic or pharmacodynamic interactions observed after concomitant administration of naproxen or aspirin (acetylsalicylic acid) with XARELTO.","","ncit:negative","ncit:Qualitative","no pharmacokinetic or pharmacodynamic interactions observed after concomitant administration of naproxen or aspirin (acetylsalicylic acid) with XARELTO.","XARELTO","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","naproxen","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/036db1f2-52b3-42a0-acf9-817b7ba8c724.html","2015-12-08 19:04:34 -0700","DDI-clinical-trial","evidence-challenges","in a maintenance trial of bipolar patients did not affect mean therapeutic valproate levels. ","Population pharmacokinetic analysis of schizophrenic patients enrolled in controlled clinical trials has not revealed evidence of any clinically significant pharmacokinetic interactions with benztropine, propranolol, or lorazepam. The absolute bioavailability of a 20 mg dose under fed conditions is approximately 60%. The absorption of ziprasidone is increased up to two-fold in the presence of food","","ncit:negative","ncit:quantitative",,"propranolol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","ziprasidone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a0da0dba-a56d-486b-a45b-e8a7cdfbeac6.html","2016-05-10 10:30:28 -0700","DDI-clinical-trial","evidence-supports"," Macrolide Antibiotics ","Coadministration of erythromycin increased the maximum plasma concentration of triazolam by 46%, decreased clearance by 53%, and increased half-life by 35%; caution and consideration of appropriate triazolam dose reduction are recommended. Similar caution should be observed during coadministration with clarithromycin and other macrolide antibiotics.","","ncit:positive","ncit:quantitative",,"triazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","erythromycin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","53","Percent","Decrease","46","Percent","Increase","35","Percent","Increase" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/39a5dae2-49f7-4662-9eac-aa7b4c7807a4.html","2016-05-09 16:39:00 -0700","DDI-clinical-trial","evidence-supports","decreased each other's C max by 22%. ","Coadministration of eszopiclone 3 mg to subjects receiving ketoconazole, a potent inhibitor of CYP3A4, 400 mg daily for 5 days, resulted in a 2.2-fold increase in exposure to eszopiclone. Cmax and t1/2 were increased 1.4-fold and 1.3-fold, respectively. LUNESTA would not be expected to alter the clearance of drugs metabolized by common CYP450 enzymes [see Warnings and Precautions (5.7), Dosage and Administration (2.3)]. ","","ncit:positive","ncit:quantitative",,"eszopiclone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","3","ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","400","UNK","Oral","5","Daily","Oral","5","UNK","2.2","Percent","Increase","UNK","UNK","UNK","1.4","Fold","Increase","1.3","Fold","Increase" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f0c6f5f-b906-4c8f-8580-3939a476a1c1.html","2016-01-11 10:40:30 -0700","drug-drug-interaction","evidence-supports","CYP2D6 and CYP3A4 Inhibitors ","Concomitant treatment with CLOZARIL and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology (12.3)]. Use caution and monitor patients closely when using such inhibitors. Consider reducing the CLOZARIL dose [see Dosage and Administration (2.6)","","ncit:positive","ncit:Qualitative","paroxetine can increase clozapine levels","paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"clozapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 17:32:29 -0700","DDI-clinical-trial","evidence-challenges","75 mg produced additive effects on decreased alertness and impaired psychomotor performance for 2 to 4 hours after administration. The interaction was pharmacodynamic with no alteration of the pharmacokinetics of either drug. ","Paroxetine: Coadministration of a single dose of Zaleplon 20 mg and paroxetine 20 mg daily for 7 days did not produce any interaction on psychomotor performance. Additionally, paroxetine did not alter the pharmacokinetics of Zaleplon, reflecting the absence of a role of CYP2D6 in zaleplon's metabolism.","","ncit:negative","ncit:quantitative","paroxetine did not alter the pharmacokinetics of Zaleplon, reflecting the absence of a role of CYP2D6 in zaleplon's metabolism.","zaleplon","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","20","paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","SD","Oral","1","Daily","Oral","7","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 12:14:12 -0800","drug-drug-interaction","evidence-supports","are necessary when the two drugs are given concomitantly. Subsequent dose adjustments should be made on the basis of clinical response. ","Lithium – In 13 healthy subjects the coadministration of nefazodone (200 mg BID) with lithium (500 mg BID) for 5 days (steady-state conditions) was found to be well tolerated. When the two drugs were coadministered, there were no changes in the steady-state pharmacokinetics of either lithium, nefazodone, or its metabolite HO-NEF; however, there were small decreases in the steady-state plasma concentrations of two nefazodone metabolites, mCPP and triazole-dione, which are considered not to be of clinical significance. Therefore, no dosage adjustment of either lithium or nefazodone is required when they are coadministered.","","ncit:positive","ncit:Qualitative","small decreases in the steady-state plasma concentrations","Lithium","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"triazole-dione","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/036db1f2-52b3-42a0-acf9-817b7ba8c724.html","2015-12-08 19:00:54 -0700","DDI-clinical-trial","evidence-challenges","dextromethorphan / dextrorphan ratio. ","A pharmacokinetic interaction of ziprasidone with valproate is unlikely due to the lack of common metabolic pathways for the two drugs. Ziprasidone dosed adjunctively to valproate in a maintenance trial of bipolar patients did not affect mean therapeutic valproate levels.","","ncit:negative","ncit:quantitative",,"ziprasidone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","valproate","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 11:01:28 -0700","drug-drug-interaction","evidence-challenges","and Drug Interactions (7) ] . ","In dedicated studies conducted in healthy subjects, famotidine, atenolol, prasugrel, and enoxaparin did not meaningfully alter the pharmacokinetics of apixaban.","","ncit:negative","ncit:Qualitative","atenolol did not meaningfully alter the pharmacokinetics of apixaban","apixaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","atenolol","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/520428f1-2cd5-447f-8782-c8505ce65b72.html","2016-03-30 16:14:20 -0700","drug-drug-interaction","evidence-supports","is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. ","Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin. (See CONTRAINDICATIONS, WARNINGS, Myopathy/Rhabdomyolysis, and CLINICAL PHARMACOLOGY, Pharmacokinetics.)","","ncit:positive","ncit:Qualitative","Telithromycin is a strong inhibitor of CYP3A4 and reduces the elimination of lovastatin","telithromycin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"lovastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ba74e3cd-b06f-4145-b284-5fd6b84ff3c9.html","2016-04-11 16:05:23 -0700","drug-drug-interaction","evidence-challenges","I","n clinical studies exploring CYP3A4, CYP2C9, P-gp and other pathways, dabigatran did not meaningfully alter the pharmacokinetics of amiodarone, atorvastatin, clarithromycin, diclofenac, clopidogrel, digoxin, pantoprazole, or ranitidine.","","ncit:negative","ncit:Qualitative","dabigatran did not meaningfully alter the pharmacokinetics of atorvastatin","atorvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","dabigatran","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 13:21:48 -0700","DDI-clinical-trial","evidence-challenges"," — ","Olanzapine (10 mg daily for 2 weeks) did not affect the steady state plasma concentrations of valproate",". Therefore, concomitant","ncit:negative","ncit:quantitative",,"valproate","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","Olanzapine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","10","UNK","Oral","UNK","QD","Oral","14","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 18:09:38 -0700","DDI-clinical-trial","evidence-challenges","is reported to be a weak inhibitor of aldehyde oxidase in rat liver, but its inhibitory effects in human liver are not known. "," There is no pharmacokinetic interaction between zaleplon and diphenhydramine following the administration of a single dose (10 mg and 50 mg, respectively) of each drug. However, because both of these compounds have CNS effects, an additive pharmacodynamic effect is possible.","","ncit:negative","ncit:quantitative","no pharmacokinetic interaction between zaleplon and diphenhydramine","zaleplon","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","10","diphenhydramine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","50","SD","Oral","1","SD","Oral","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 12:44:17 -0700","drug-drug-interaction","evidence-challenges"," — ","Warfarin (20 mg single dose) did not affect olanzapine pharmacokinetics ","","ncit:negative","ncit:Qualitative","Single dose warfarin did not affect olanzapine pharmacokinetics","olanzapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Warfarin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 16:42:40 -0700","DDI-clinical-trial","evidence-supports","increased by 150% and 60%, respectively. Similar increases in pharmacodynamic effects were also observed. ","Clarithromycin (combined P-gp and strong CYP3A4 inhibitor): Single-dose rivaroxaban AUC and Cmax increased by 50% and 40%, respectively. The smaller increases in exposure observed for clarithromycin compared to ketoconazole or ritonavir may be due to the relative difference in P-gp inhibition.","","ncit:positive","ncit:quantitative",,"clarithromycin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","rivaroxaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","50","UNK","Increase","UNK","UNK","UNK","40","UNK","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:32:16 -0700","drug-drug-interaction","evidence-supports"," is not known."," Rifampin Rifampin, a CYP3A4 inducer, significantly reduced the exposure to and the pharmacodynamic effects of zolpidem. Use of Rifampin in combination with zolpidem may decrease the efficacy of zolpidem.","","ncit:positive","ncit:Qualitative","significantly reduced the exposure to","Rifampin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"zolpidem","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2015-11-29 14:49:58 -0700","DDI-clinical-trial","evidence-supports","","Paroxetine: Co-administration of paroxetine (20 mg/day for 5 to 8 days), a potent inhibitor of CYP2D6, with multiple doses of iloperidone (8 or 12 mg twice daily) to patients with schizophrenia ages 18 to 65 years resulted in increased mean steady-state peak concentrations of iloperidone and its metabolite P88, by about 1.6-fold, and decreased mean steady-state peak concentrations of its metabolite P95 by one-half. Iloperidone doses should be reduced by one-half when administered with paroxetine. ","When","ncit:positive","ncit:quantitative",,"iloperidone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","8 or 12","paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","BID","Oral","UNK","Daily","Oral","5 to 8","UNK","UNK","UNK","UNK","UNK","UNK","UNK","1.6","Fold","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e1e5249-1cb7-4cc2-ad5a-cdeeee2f494f.html","2016-02-16 16:45:41 -0700","drug-drug-interaction","evidence-supports","potentiated the cognitive and motor effects of alcohol in a clinical trial in subjects with selected psychotic disorders, and alcoholic beverages should be limited while taking quetiapine . ","Quetiapine exposure is increased by the prototype CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.)","","ncit:positive","ncit:Qualitative","quetiapine exposure is increased by CYP3A4 inhibitors","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"Quetiapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d76d5540-7bae-4719-8166-f2a9106338df.html","2016-05-09 19:47:38 -0700","DDI-clinical-trial","evidence-supports",". The effect of inhibitors of other P450 enzymes on the pharmacokinetics of zolpidem is unknown. ","A single-dose interaction study with zolpidem tartrate 10 mg and itraconazole 200 mg at steady-state levels in male volunteers resulted in a 34% increase in AUC0–∞ of zolpidem tartrate. There were no pharmacodynamic effects of zolpidem detected on subjective drowsiness, postural sway, or psychomotor performance.","","ncit:positive","ncit:quantitative",,"itraconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","zolpidem","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","10","SD","Oral","1","UNK","Oral","UNK","UNK","34","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a0da0dba-a56d-486b-a45b-e8a7cdfbeac6.html","2016-05-10 13:45:18 -0400","DDI-clinical-trial","evidence-supports"," Ranitidine ","Coadministration of ranitidine increased the maximum plasma concentration of triazolam by 30%, increased the area under the concentration curve by 27%, and increased half-life by 3.3%. Caution is recommended during coadministration with triazolam.","","ncit:positive","ncit:quantitative",,"triazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","ranitidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","UNK","Oral","UNK","UNK","Oral","UNK","UNK","27","Percent","Increase","UNK","UNK","UNK","30","Percent","Increase","3.3","Percent","Increase" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2015-11-29 14:35:23 -0700","DDI-clinical-trial","evidence-supports","elimination and cause increased blood levels. ","Ketoconazole: Co-administration of ketoconazole (200 mg twice daily for 4 days), a potent inhibitor of CYP3A4, with a 3 mg single dose of iloperidone to 19 healthy volunteers, ages 18 to 45 years, increased the area under the curve (AUC) of iloperidone and its metabolites P88 and P95 by 57%, 55% and 35%, respectively. Iloperidone doses should be reduced by about one-half when administered with ketoconazole or other strong inhibitors of CYP3A4 (e.g., itraconazole). Weaker inhibitors (e.g., erythromycin, grapefruit juice) have not been studied. When the CYP3A4 inhibitor is withdrawn from the combination therapy, the iloperidone dose should be returned to the previous level.","","ncit:positive","ncit:quantitative",,"ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","P88","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","3","SD","Oral","1","BID","Oral","4","19","55","Percent","Increase","UNKUNUNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/44dcbf97-99ec-427c-ba50-207e0069d6d2.html","2016-03-31 10:15:25 -0700","drug-drug-interaction","evidence-supports"," 7.3 Rifampin ","Rifampin significantly increased pitavastatin exposure. In patients taking rifampin, a dose of LIVALO 2 mg once daily should not be exceeded [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative","Rifampin significantly increased pitavastatin exposure. Study details in section 12 Table 3","Rifampin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"pitavastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/10db92f9-2300-4a80-836b-673e1ae91610.html","2016-05-01 17:53:05 -0700","DDI-clinical-trial","evidence-challenges","I","n addition, there were no significant pharmacokinetic interactions observed in studies comparing concomitant rivaroxaban 20 mg and 7.5 mg single dose of midazolam (substrate of CYP3A4), 0.375 mg once-daily dose of digoxin (substrate of P-gp), ","or 20 mg once daily dose of","ncit:negative","ncit:quantitative","no significant pharmacokinetic interactions observed","digoxin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",".375","rivaroxaban","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","20","UNK","Oral","UNK","QD","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/9c4bedb4-2d59-4fcd-aad7-fce988cd96d8.html","2016-02-29 14:20:16 -0700","drug-drug-interaction","evidence-supports","Thioridazine hydrochloride tablet use should be avoided in combination with other drugs that are known to prolong the QTc interval and in patients with congenital long QT syndrome or a history of cardiac arrhythmias. ","Reduced cytochrome P450 2D6 isozyme activity drugs that inhibit this isozyme (e.g., fluoxetine and paroxetine) and certain other drugs (e.g., fluvoxamine, propranolol, and pindolol) appear to appreciably inhibit the metabolism of thioridazine. The resulting elevated levels of thioridazine would be expected to augment the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as Torsades de pointes type arrhythmias.","","ncit:positive","ncit:Qualitative","appears to appreciably inhibit the metabolism of thioridazine and result in elevated levels of thioridazine","thioridazine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 10:50:15 -0800","DDI-clinical-trial","evidence-challenges","are necessary when the two drugs are given concomitantly. Subsequent dose adjustments should be made on the basis of clinical response. ","Lithium – In 13 healthy subjects the coadministration of nefazodone (200 mg BID) with lithium (500 mg BID) for 5 days (steady-state conditions) was found to be well tolerated. When the two drugs were coadministered, there were no changes in the steady-state pharmacokinetics of either lithium, nefazodone, or its metabolite HO-NEF; however, there were small decreases in the steady-state plasma concentrations of two nefazodone metabolites, mCPP and triazole-dione, which are considered not to be of clinical significance. Therefore, no dosage adjustment of either lithium or nefazodone is required when they are coadministered.","","ncit:negative","ncit:quantitative",,"nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","Lithium","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","500","BID","Oral","5","BID","Oral","5","13","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2015-12-17 18:44:54 -0700","DDI-clinical-trial","evidence-supports","fluoxetine (20 mg twice daily). ","Midazolam (a sensitive CYP 3A4 substrate): A study in patients with schizophrenia showed a less than 50% increase in midazolam total exposure at iloperidone steady state (14 days of oral dosing at up to 10 mg iloperidone twice daily) and no effect on midazolam Cmax. Thus, an interaction between iloperidone and other CYP3A4 substrates is unlikely.","","ncit:positive","ncit:quantitative","less than 50% increase in midazolam total exposure","iloperidone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","up to 10","midazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","UNK","UNK","Oral","UNK","BID","Oral","14","UNK","UNK","UNK","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e1e5249-1cb7-4cc2-ad5a-cdeeee2f494f.html","2016-02-16 16:45:41 -0700","drug-drug-interaction","evidence-supports","potentiated the cognitive and motor effects of alcohol in a clinical trial in subjects with selected psychotic disorders, and alcoholic beverages should be limited while taking quetiapine . ","Quetiapine exposure is increased by the prototype CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.)","","ncit:positive","ncit:Qualitative","quetiapine exposure is increased by CYP3A4 inhibitors","Quetiapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","ritonavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-30 15:06:21 -0700","drug-drug-interaction","evidence-supports"," 7.1 Cyclosporine ","Cyclosporine coadministration increases fluvastatin exposure. Therefore, in patients taking cyclosporine, therapy should be limited to fluvastatin 20 mg twice daily [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative","Concomitant cyclosporin increases fluvastatin exposure. Details in Section 12 Table 3","Cyclosporine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"fluvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e1e5249-1cb7-4cc2-ad5a-cdeeee2f494f.html","2016-02-16 16:45:41 -0700","drug-drug-interaction","evidence-supports","","Quetiapine exposure is increased by the prototype CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.). and decreased by the prototype CYP3A4 inducers (e..g, phenytoin, carbamazepine, rifampin, avasimibe, St. John’s wort etc.)."," Dose adjustment of","ncit:positive","ncit:Qualitative","quetiapine exposure is decreased by CYP3A4 inducers","rifampin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"Quetiapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c6e131fe-e7df-4876-83f7-9156fc4e8228.html","2016-03-14 14:59:55 -0700","drug-drug-interaction","evidence-supports","7.7 Rifampin or other Inducers of Cytochrome P450 3A4 ","Concomitant administration of LIPITOR with inducers of cytochrome P450 3A4 (e.g., efavirenz, rifampin) can lead to variable reductions in plasma concentrations of atorvastatin. Due to the dual interaction mechanism of rifampin, simultaneous co-administration of LIPITOR with rifampin is recommended, as delayed administration of LIPITOR after administration of rifampin has been associated with a significant reduction in atorvastatin plasma concentrations. ","","ncit:positive","ncit:Qualitative","administration of rifampin has been associated with a significant reduction in atorvastatin plasma concentrations.\n\tadministration of rifampin has been associated with a significant reduction in atorvastatin plasma concentrations.\n\tadministration of rifampin has been associated with a significant reduction in atorvastatin plasma concentrations.","rifampin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"atorvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-31 16:00:41 -0400","drug-drug-interaction","evidence-challenges","fluvastatin sodium extended-release tablets, 80 mg QD for 19 days ↓2% ↑27% ","Data from drug-drug interaction studies involving fluvastatin and coadministration of either gemfibrozil, tolbutamide or losartan indicate that the PK disposition of either gemfibrozil, tolbutamide or losartan is not significantly altered when coadministered with fluvastatin","","ncit:negative","ncit:Qualitative","PK disposition of losartan is not significantly altered when coadministered with fluvastatin.","losartan","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluvastatin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1fd0ba23-962e-427f-8b9d-2cf8f64d0f95.html","2016-03-31 14:25:54 -0400","drug-drug-interaction","evidence-challenges"," 7.6 Fenofibrate ","When CRESTOR was coadministered with fenofibrate, no clinically significant increase in the AUC of rosuvastatin or fenofibrate was observed. Because it is known that the risk of myopathy during treatment with HMG-CoA reductase inhibitors is increased with concomitant use of fenofibrates, caution should be used when prescribing fenofibrates with CRESTOR [seeWarnings and Precautions (5.1) andClinical Pharmacology (12.3)].","","ncit:negative","ncit:Qualitative","When CRESTOR was coadministered with fenofibrate, no clinically significant increase in the AUC of rosuvastatin or fenofibrate was observed. Study details in Section 12 Table 4","rosuvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fenofibrate","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/aad8b373-0aec-4efb-8e61-3d8114b31127.html","2016-03-31 12:59:13 -0700","drug-drug-interaction","evidence-challenges","fluvastatin sodium extended-release tablets, 80 mg QD for 19 days ↓2% ↑27% ","Data from drug-drug interaction studies involving fluvastatin and coadministration of either gemfibrozil, tolbutamide or losartan indicate that the PK disposition of either gemfibrozil, tolbutamide or losartan is not significantly altered when coadministered with fluvastatin.","","ncit:negative","ncit:Qualitative","PK disposition of gemfibrozil is not significantly altered when coadministered with fluvastatin.","gemfibrozil","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluvastatin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2015-11-29 14:46:00 -0700","DDI-clinical-trial","evidence-supports","dose should be returned to the previous level. ","Fluoxetine: Co-administration of fluoxetine (20 mg twice daily for 21 days), a potent inhibitor of CYP2D6, with a single 3 mg dose of iloperidone to 23 healthy volunteers, ages 29 to 44 years, who were classified as CYP2D6 extensive metabolizers, increased the AUC of iloperidone and its metabolite P88, by about 2- to 3-fold, and decreased the AUC of its metabolite P95 by one-half. Iloperidone doses should be reduced by one-half when administered with fluoxetine. ","","ncit:positive","ncit:quantitative",,"fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","P95","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","3","SD","Oral","1","BID","Oral","21","23","50","Percent","Decrease","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/2f44db39-e1d9-451e-ba31-e4b10366a430.html","2016-05-09 18:12:14 -0700","DDI-clinical-trial","evidence-supports"," metabolism. ","Concomitant administration of Zaleplon (10 mg) and cimetidine (800 mg) produced an 85% increase in the mean Cmax and AUC of zaleplon. An initial dose of 5 mg should be given to patients who are concomitantly being treated with cimetidine (see DOSAGE AND ADMINISTRATION).","","ncit:positive","ncit:quantitative",,"zaleplon","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","10","cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","800","UNK","UNK","UNK","UNK","Oral","UNK","UNK","85","Percent","Increase","UNK","UNK","UNK","85","Percent","Increase","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ee49f3b1-1650-47ff-9fb1-ea53fe0b92b6.html","2016-03-14 17:06:08 -0400","DDI-clinical-trial","evidence-challenges","aripiprazole pharmacokinetics ","The effects of ABILIFY on the exposures of other drugs are summarized in Figure 21. A population PK analysis in patients with major depressive disorder showed no substantial change in plasma concentrations of fluoxetine (20 mg/day or 40 mg/day), paroxetine CR (37.5 mg/day or 50 mg/day), or sertraline (100 mg/day or 150 mg/day) dosed to steady-state. The steady-state plasma concentrations of fluoxetine and norfluoxetine increased by about 18% and 36%, respectively, and concentrations of paroxetine decreased by about 27%. The steady-state plasma concentrations of sertraline and desmethylsertraline were not substantially changed when these antidepressant therapies were coadministered with aripiprazole.","","ncit:negative","ncit:quantitative","The steady-state plasma concentrations of sertraline and desmethylsertraline were not substantially changed when these antidepressant therapies were coadministered with aripiprazole.","desmethylsertraline","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","100-150","ABILIFY","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","UNK","Daily","Oral","UNK","UNK","Oral","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-29 11:47:05 -0800","DDI-clinical-trial","evidence-challenges","are coadministered; plasma level monitoring for digoxin is recommended. ","Propranolol – The coadministration of nefazodone (200 mg BID) and propranolol (40 mg BID) for 5.5 days to healthy male volunteers (n = 18), including 3 poor and 15 extensive CYP2D6 metabolizers, resulted in 30% and 14% reductions in Cmax and AUC of propranolol, respectively, and a 14% reduction in Cmax for the metabolite, 4-hydroxypropranolol. The kinetics of nefazodone, hydroxynefazodone, and triazole-dione were not affected by coadministration of propranolol. However, Cmax, Cmin, and AUC of m-chlorophenylpiperazine were increased by 23%, 54%, and 28%, respectively. No change in initial dose of either drug is necessary and dose adjustments should be made on the basis of clinical response.","","ncit:negative","ncit:quantitative",,"triazole-dione","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","200","propranolol","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","BID","Oral","5.5","BID","Oral","5.5","18","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/d5051fbc-846b-4946-82df-341fb1216341.html","2016-02-16 13:14:56 -0700","DDI-clinical-trial","evidence-challenges"," — ","Administration of intramuscular lorazepam (2 mg) 1 hour after intramuscular olanzapine for injection (5 mg) did not significantly affect the pharmacokinetics of olanzapine, unconjugated lorazepam, or total lorazepam."," However, this co-administration of intramuscular","ncit:negative","ncit:quantitative","Formulation entered as IV but actually IM","lorazepam","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","2","olanzapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","5","SD","IV","1","SD","IV","1","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/43452bf8-76e7-47a9-a5d8-41fe84d061f0.html","2015-11-29 14:38:11 -0700","DDI-clinical-trial","evidence-supports","elimination and cause increased blood levels. ","Ketoconazole: Co-administration of ketoconazole (200 mg twice daily for 4 days), a potent inhibitor of CYP3A4, with a 3 mg single dose of iloperidone to 19 healthy volunteers, ages 18 to 45 years, increased the area under the curve (AUC) of iloperidone and its metabolites P88 and P95 by 57%, 55% and 35%, respectively. Iloperidone doses should be reduced by about one-half when administered with ketoconazole or other strong inhibitors of CYP3A4 (e.g., itraconazole). Weaker inhibitors (e.g., erythromycin, grapefruit juice) have not been studied. When the CYP3A4 inhibitor is withdrawn from the combination therapy, the iloperidone dose should be returned to the previous level.","","ncit:positive","ncit:quantitative",,"P95","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","3","ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","SD","Oral","1","BID","Oral","4","19","35","Percent","Increase","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e9481622-7cc6-418a-acb6-c5450daae9b0.html","2016-04-12 11:02:59 -0700","drug-drug-interaction","evidence-challenges","did not meaningfully alter the pharmacokinetics of apixaban . ","In studies conducted in healthy subjects, apixaban did not meaningfully alter the pharmacokinetics of digoxin, naproxen, atenolol, prasugrel, or acetylsalicylic acid.","","ncit:negative","ncit:Qualitative","pixaban did not meaningfully alter the pharmacokinetics of digoxin","digoxin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","apixaban","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, diff --git a/translation/RDB_ETL/pkddi-katrina-latest-08142016.csv b/translation/RDB_ETL/pkddi-katrina-latest-08142016.csv deleted file mode 100644 index d14aa45..0000000 --- a/translation/RDB_ETL/pkddi-katrina-latest-08142016.csv +++ /dev/null @@ -1,449 +0,0 @@ -"source","date","assertionType","evidenceType","exactText","modality","statementType","comment","drug1Lab","drug1Type","drug1Role","dose1","drug2Lab","drug2Type","drug2Role","dose2","objectRegimens","objectFormulation","objectDuration","preciptRegimens","preciptFormulation","preciptDuration","numOfParticipants","auc","aucType","aucDirection","cl","clType","clDirection","cmax","cmaxType","cmaxDirection","t12","t12Type","t12Direction" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:48:50 -0400","drug-drug-interaction","evidence-supports","Teriflunomide inhibits the activity of OAT3 in vivo. In patients taking AUBAGIO, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) which are OAT3 substrates as required [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"furosemide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ea35caf8-c8c8-481a-97a2-25f68cbc240b.html","2015-10-29 11:09:04 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction",,"quinidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:42:22 -0400","drug-drug-interaction","evidence-supports","No dose adjustment of alprazolam, ibuprofen, levothyroxine, olanzapine, risperdione, warfarin, or strong CYP3A4 inhibitors (e.g., ketoconazole) is necessary when these drugs are used in combination with EMSAM. EMSAM had no clinically relevant effect on pharmacokinetics of these drugs.","ncit:negative","ncit:Qualitative",,"olanzapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:17:34 -0400","DDI-clinical-trial","evidence-supports","Risperidone In subjects who had received EMSAM 6 mg per 24 hours for 10 days, co-administration with risperidone (2 mg per day for 7 days), a substrate for CYP2D6, did not affect the pharmacokinetics of selegiline or risperidone [see Drug Interactions (7.4) and (7.5)]. Warfarin","ncit:negative","ncit:quantitative",,"EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","6","risperidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","2","Daily","Oral","7","Daily","transdermal","10","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e338e89-3cf2-48eb-b6e2-a06c608c6513.html","2015-08-20 11:17:13 -0400","DDI-clinical-trial","evidence-supports","In an in vivo drug-drug interaction trial, the Cmax and AUC of dextromethorphan (CYP2D6 substrate) were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily (plus prednisone 5 mg twice daily). The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold [see Drug Interactions (7.2)].","ncit:positive","ncit:quantitative",,"dextromethorphan","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","1000","abiraterone acetate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","30","UNK","UNK","Unk","Daily","UNK","Unk","Unk","2.9","Fold","Increase","Unk","UNK","UNK","2.8","Fold","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f356c1b-96bd-4ef1-960c-91cf4905e6b1.html","2015-11-02 16:13:06 -0500","DDI-clinical-trial","evidence-supports","Olanzapine — Fluoxetine (60 mg single dose or 60 mg daily dose for 8 days) causes a small (mean 16%) increase in the maximum concentration of olanzapine and a small (mean 16%) decrease in olanzapine clearance. The magnitude of the impact of this factor is small in comparison to the overall variability between individuals, and therefore dose modification is not routinely recommended. ","ncit:positive","ncit:quantitative",,"olanzapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","Fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","60","UNK","UNK","Unk","Daily","Oral","8","Unk","Unk","UNK","UNK","16","Percent","Decrease","16","Percent","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-09-14 11:21:10 -0400","drug-drug-interaction","evidence-supports","An in vivo interaction study involving the coadministration under steady-state conditions of paroxetine and terfenadine, a substrate for cytochrome CYP3A4, revealed no effect of paroxetine on terfenadine pharmacokinetics.","ncit:negative","ncit:Qualitative",,"paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","terfenadine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/cc9e1c8c-0e2b-44e2-878b-27057f786be9.html","2015-08-20 13:57:35 -0400","drug-drug-interaction","evidence-supports","Experience with GILENYA in patients receiving concurrent therapy with drugs that slow the heart rate or atrioventricular conduction (e.g., beta blockers, digoxin, or heart rate-slowing calcium channel blockers such as diltiazem or verapamil) is limited. Because initiation of GILENYA treatment may result in an additional decrease in heart rate, concomitant use of these drugs during GILENYA initiation may be associated with severe bradycardia or heart block. Seek advice from the prescribing physician regarding the possibility to switch to drugs that do not slow the heart rate or atrioventricular conduction before initiating GILENYA. Patients who cannot switch, should have overnight continuous ECG monitoring after the first dose [see Dosage and Administration (2) and Warnings and Precautions (5.1)]","ncit:positive","ncit:Qualitative",,"beta blockers","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","GILENYA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:46:43 -0400","DDI-clinical-trial","evidence-supports","Digoxin–In a placebo-controlled trial in normal volunteers, administration of sertraline for 17 days (including 200 mg/day for the last 10 days) did not change serum digoxin levels or digoxin renal clearance.","ncit:negative","ncit:quantitative",,"digoxin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","UNK","UNK","Unk","Daily","Oral","17","10","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:32:33 -0500","DDI-clinical-trial","evidence-supports","Digoxin - In subjects who had received 21 days of 40 mg/day Celexa, combined administration of Celexa and digoxin (single dose of 1 mg) did not significantly affect the pharmacokinetics of either citalopram or digoxin.","ncit:negative","ncit:quantitative",,"citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","40","digoxin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","1","Daily","Oral","21","SD","Oral","1","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1809bcb4-5fcc-45ca-986a-4fa5edcd4b5e.html","2015-09-29 09:58:27 -0400","drug-drug-interaction","evidence-supports","The plasma concentration of CMI has been reported to be increased by the concomitant administration of haloperidol; plasma levels of several closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of methylphenidate or hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by the concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin), and such an effect may be anticipated with CMI as well. Administration of CMI has been reported to increase the plasma levels of phenobarbital, if given concomitantly (see CLINICAL PHARMACOLOGY, Interactions).","ncit:positive","ncit:Qualitative",,"tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","hepatic enzyme inducers","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:36:27 -0400","DDI-clinical-trial","evidence-supports","In a placebo-controlled trial in normal volunteers, the administration of two doses of sertraline did not significantly alter steady-state lithium levels or the renal clearance of lithium.","ncit:negative","ncit:quantitative",,"sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","lithium","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","Lorazepam-There was no pharmacokinetic interaction between a single dose of Savella (50 mg) and lorazepam (1.5 mg). ","ncit:negative","ncit:quantitative",,"lorazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","50","Savella","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:object-drug-of-interaction","1.5","SD","tablet","1","SD","tablet","1","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-10-28 14:38:28 -0400","DDI-clinical-trial","evidence-supports","In vitro drug interaction studies reveal that paroxetine inhibits CYP2D6. Clinical drug interaction studies have been performed with substrates of CYP2D6 and show that paroxetine can inhibit the metabolism of drugs metabolized by CYP2D6 including desipramine, risperidone, and atomoxetine (see PRECAUTIONS: Drug Interactions)","ncit:positive","ncit:quantitative",,"paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","atomoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary","ncit:positive","ncit:Qualitative",,"flecainide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-10-28 15:23:31 -0400","DDI-clinical-trial","evidence-supports","In a controlled study of healthy volunteers, after paroxetine was titrated to 60 mg daily, coadministration of a single dose of 2 mg pimozide was associated with mean increases in pimozide AUC of 151% and Cmax of 62%, compared to pimozide administered alone. The increase in pimozide AUC and Cmax is due to the CYP2D6 inhibitory properties of paroxetine. Due to the narrow therapeutic index of pimozide and its known ability to prolong the QT interval, concomitant use of pimozide and paroxetine is contraindicated (see CONTRAINDICATIONS).","ncit:positive","ncit:quantitative",,"pimozide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","2","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","60","SD","Oral","1","Daily","Oral","Unk","Unk","151","Percent","Increase","Unk","UNK","UNK","62","Percent","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:56:21 -0500","DDI-clinical-trial","evidence-supports","Carbamazepine - Combined administration of Celexa (40 mg/day for 14 days) and carbamazepine (titrated to 400 mg/day for 35 days) did not significantly affect the pharmacokinetics of carbamazepine, a CYP3A4 substrate. Although trough citalopram plasma levels were unaffected, given the enzyme-inducing properties of carbamazepine, the possibility that carbamazepine might increase the clearance of citalopram should be considered if the two drugs are coadministered.","ncit:negative","ncit:quantitative",,"Celexa","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","40","carbamazepine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","400","Daily","Oral","35","Daily","Oral","14","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/55816042-946d-4bec-9461-bd998628ff45.html","2015-10-14 11:57:06 -0400","drug-drug-interaction","evidence-supports","Rifampin has been reported to substantially decrease the plasma concentrations of the following antiviral drugs: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir. These antiviral drugs must not be co-administered with rifampin. (See CONTRAINDICATIONS.) ","ncit:positive","ncit:Qualitative",,"Rifampin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","tipranavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:13:01 -0400","DDI-clinical-trial","evidence-supports","Ketoconazole Seven-day treatment with ketoconazole (200 mg per day), a potent inhibitor of CYP3A4, did not affect the steady-state pharmacokinetics of selegiline in subjects who received EMSAM 6 mg per 24 hours for 7 days and no differences in the pharmacokinetics of ketoconazole were observed [see Drug Interactions (7.4) and (7.5)]. ","ncit:negative","ncit:quantitative",,"selegiline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","6","ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","200","Daily","Oral","7","Daily","transdermal","7","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-09-14 11:32:07 -0400","drug-drug-interaction","evidence-supports","Coadministration of fosamprenavir/ritonavir with paroxetine significantly decreased plasma levels of paroxetine. Any dose adjustment should be guided by clinical effect (tolerability and efficacy)","ncit:positive","ncit:Qualitative",,"paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fosamprenavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:22:34 -0500","DDI-clinical-trial","evidence-supports","In subjects who had received 21 days of 40 mg/day racemic citalopram, combined administration of citalopram and digoxin (single dose of 1 mg) did not significantly affect the pharmacokinetics of either citalopram or digoxin. ","ncit:negative","ncit:quantitative",,"digoxin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","1","citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","SD","Oral","1","Daily","Oral","21","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f356c1b-96bd-4ef1-960c-91cf4905e6b1.html","2015-09-10 14:36:47 -0400","drug-drug-interaction","evidence-supports","Antipsychotics — Some clinical data suggests a possible pharmacodynamic and/or pharmacokinetic interaction between SSRIs and antipsychotics. Elevation of blood levels of haloperidol and clozapine has been observed in patients receiving concomitant fluoxetine. ","ncit:positive","ncit:Qualitative",,"fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","haloperidol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a16297df-3158-48db-85e5-5cd506885556.html","2015-09-29 09:27:10 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine, cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"quinidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-09-10 15:01:13 -0400","drug-drug-interaction","evidence-supports","Significantly increased plasma TCA levels have been reported with the coadministration of fluvoxamine maleate and amitriptyline, clomipramine or imipramine. Caution is indicated with the coadministration of fluvoxamine maleate tablets and TCAs; plasma TCA concentrations may need to be monitored, and the dose of TCA may need to be reduced.","ncit:positive","ncit:Qualitative",,"fluvoxamine maleate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","imipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ea35caf8-c8c8-481a-97a2-25f68cbc240b.html","2015-09-29 09:04:36 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/829a4f51-c882-4b64-81f3-abfb03a52ebe.html","2015-10-29 09:10:04 -0400","DDI-clinical-trial","evidence-supports","Duloxetine is a moderate inhibitor of CYP2D6. When duloxetine was administered (at a dose of 60 mg twice daily) in conjunction with a single 50 mg dose of desipramine, a CYP2D6 substrate, the AUC of desipramine increased 3-fold [see WARNINGS AND PRECAUTIONS (5.12)]. ","ncit:positive","ncit:quantitative",,"desipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","50","duloxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","60","SD","Oral","1","BID","Oral","Unk","Unk","3","Fold","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:33:12 -0400","DDI-clinical-trial","evidence-supports","In healthy male patients (n=18), phenytoin (200 mg daily) increased mirtazapine (30 mg daily) clearance about 2-fold, resulting in a decrease in average plasma mirtazapine concentrations of 45%. Mirtazapine did not significantly affect the pharmacokinetics of phenytoin.","ncit:positive","ncit:quantitative",,"phenytoin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","mirtazapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","30","Daily",,"Unk","Daily","Oral","Unk","18","Unk","UNK","UNK","2","Fold","Increase","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","Pregabalin-There were no clinically significant changes in the steady-state pharmacokinetics of milnacipran or pregabalin following twice a day co-administration of 50 mg milnacipran and 150 mg pregabalin. ","ncit:negative","ncit:quantitative",,"pregabalin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","50","milnacipran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","150","BID","tablet","Unk","BID","tablet","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 13:28:11 -0400","DDI-clinical-trial","evidence-supports","Ibuprofen In subjects who had received EMSAM 6 mg per 24 hours for 11 days, combined administration with the CYP2C9 substrate ibuprofen (800 mg single dose) did not affect the pharmacokinetics of either selegiline or ibuprofen [see Drug Interactions (7.4) and (7.5)]. ","ncit:negative","ncit:quantitative",,"ibuprofen","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","800","EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:object-drug-of-interaction","6","Daily","transdermal","11","SD","Oral","1","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a16297df-3158-48db-85e5-5cd506885556.html","2015-09-29 09:27:10 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine, cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","selective serotonin reuptake inhibitors","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/cc9e1c8c-0e2b-44e2-878b-27057f786be9.html","2015-08-20 13:57:35 -0400","drug-drug-interaction","evidence-supports","Experience with GILENYA in patients receiving concurrent therapy with drugs that slow the heart rate or atrioventricular conduction (e.g., beta blockers, digoxin, or heart rate-slowing calcium channel blockers such as diltiazem or verapamil) is limited. Because initiation of GILENYA treatment may result in an additional decrease in heart rate, concomitant use of these drugs during GILENYA initiation may be associated with severe bradycardia or heart block. Seek advice from the prescribing physician regarding the possibility to switch to drugs that do not slow the heart rate or atrioventricular conduction before initiating GILENYA. Patients who cannot switch, should have overnight continuous ECG monitoring after the first dose [see Dosage and Administration (2) and Warnings and Precautions (5.1)].","ncit:positive","ncit:Qualitative",,"digoxin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","GILENYA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1809bcb4-5fcc-45ca-986a-4fa5edcd4b5e.html","2015-09-29 11:41:50 -0400","drug-drug-interaction","evidence-supports"," Administration of CMI has been reported to increase the plasma levels of phenobarbital, if given concomitantly","ncit:positive","ncit:Qualitative",,"phenobarbital","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","CMI","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:48:50 -0400","drug-drug-interaction","evidence-supports","Teriflunomide inhibits the activity of OAT3 in vivo. In patients taking AUBAGIO, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) which are OAT3 substrates as required [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","methotrexate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:43:15 -0400","drug-drug-interaction","evidence-supports","Carbamazepine is contraindicated with MAOIs, including selegiline [see Contraindications (4), Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)]. ","ncit:positive","ncit:Qualitative",,"selegiline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Carbamazepine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports","The plasma concentration of imipramine may increase when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decrease by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), and adjustment of the dosage of imipramine may therefore be necessary.","ncit:positive","ncit:Qualitative",,"imipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:43:15 -0400","drug-drug-interaction","evidence-supports","No dose adjustment for EMSAM is needed when EMSAM is used concomitantly with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and CYP3A4 inhibitors (e.g., ketoconazole). No clinically meaningful change in selegiline exposure was seen when EMSAM was co-administered with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and ketoconazole [see Clinical Pharmacology (12.3)]. ","ncit:negative","ncit:Qualitative",,"ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:48:13 -0400","DDI-clinical-trial","evidence-supports","In healthy, CYP2D6 extensive metabolizer patients (n=32), amitriptyline (75 mg daily), at steady state, did not cause relevant changes in the pharmacokinetics of steady state mirtazapine (30 mg daily); mirtazapine also did not cause relevant changes to the pharmacokinetics of amitriptyline.","ncit:negative","ncit:quantitative",,"amitriptyline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","75","mirtazapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","30","Daily","Oral","Unk","Daily","Oral","Unk","32","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:39:59 -0400","DDI-clinical-trial","evidence-supports","Coadministration of fluvoxamine maleate 100 mg per day and propranolol 160 mg per day in normal volunteers resulted in a mean 5-fold increase (range 2 to 17) in minimum propranolol plasma concentrations. In this study, there was a slight potentiation of the propranolol-induced reduction in heart rate and reduction in the exercise diastolic pressure. ","ncit:positive","ncit:quantitative",,"propranolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","160","fluvoxamine maleate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","Daily","Oral","Unk","Daily","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","5","Fold","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ea35caf8-c8c8-481a-97a2-25f68cbc240b.html","2015-09-29 09:04:36 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","selective serotonin reuptake inhibitors","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:48:50 -0400","drug-drug-interaction","evidence-supports","Teriflunomide inhibits the activity of OAT3 in vivo. In patients taking AUBAGIO, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) which are OAT3 substrates as required [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"penicillin G","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e338e89-3cf2-48eb-b6e2-a06c608c6513.html","2015-08-20 11:10:08 -0400","DDI-clinical-trial","evidence-supports","Based on in vitro data, ZYTIGA is a substrate of CYP3A4. In a dedicated drug interaction trial, co-administration of rifampin, a strong CYP3A4 inducer, decreased exposure of abiraterone by 55%. Avoid concomitant strong CYP3A4 inducers during ZYTIGA treatment. If a strong CYP3A4 inducer must be co-administered, increase the ZYTIGA dosing frequency [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].","ncit:positive","ncit:quantitative",,"abiraterone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","rifampin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","55","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:17:34 -0400","DDI-clinical-trial","evidence-supports","Warfarin Warfarin is a substrate for CYP2C9 and CYP3A4 metabolism pathways. In healthy volunteers titrated with Coumadin®# (warfarin sodium) to clinical levels of anticoagulation (INR of 1.5 to 2), co-administration with EMSAM 6 mg per 24 hours for 7 days did not affect the pharmacokinetics of the individual warfarin enantiomers. EMSAM did not alter the clinical pharmacodynamic effects of warfarin as measured by INR, Factor VII or Factor X levels [see Drug Interactions (7.4) and (7.5)].","ncit:negative","ncit:quantitative",,"EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","6","warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","Daily","transdermal","7","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-09-29 11:28:40 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type IC antiarrhythmics propafenone and flecainide). While all the SSRIs, e.g., fluoxetine, sertraline, paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","quinidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f356c1b-96bd-4ef1-960c-91cf4905e6b1.html","2015-11-03 12:56:19 -0500","DDI-clinical-trial","evidence-supports","Tricyclic Antidepressants (TCAs) — In 2 studies, previously stable plasma levels of imipramine and desipramine have increased greater than 2- to 10-fold when fluoxetine has been administered in combination. This influence may persist for 3 weeks or longer after fluoxetine is discontinued. Thus, the dose of TCAs may need to be reduced and plasma TCA concentrations may need to be monitored temporarily when fluoxetine is coadministered or has been recently discontinued [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)]. ","ncit:positive","ncit:quantitative",,"imipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","2 to 10","Fold","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e338e89-3cf2-48eb-b6e2-a06c608c6513.html","2015-08-20 11:30:25 -0400","DDI-clinical-trial","evidence-supports","In a clinical study to determine the effects of abiraterone acetate 1,000 mg daily (plus prednisone 5 mg twice daily) on a single 100 mg dose of the CYP1A2 substrate theophylline, no increase in systemic exposure of theophylline was observed.","ncit:negative","ncit:quantitative",,"abiraterone acetate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","theophylline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","1000","SD","UNK","1","Daily","UNK","Unk","Unk","0","Percent","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","Warfarin-Steady-state milnacipran (200 mg/day) did not affect the pharmacokinetics of R-warfarin and S-warfarin or the pharmacodynamics (as assessed by measurement of prothrombin INR) of a single dose of 25 mg warfarin. The pharmacokinetics of Savella were not altered by warfarin. ","ncit:negative","ncit:quantitative",,"milnacipran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","25","warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","200","SD","tablet","1","Daily","tablet","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/7c295b64-ec39-42ec-9f02-da5b42e775e1.html","2015-08-20 10:29:59 -0400","DDI-clinical-trial","evidence-supports","In vitro studies have shown that R-bicalutamide is an inhibitor of CYP 3A4 with lesser inhibitory effects on CYP 2C9, 2C19 and 2D6 activity. Clinical studies have shown that with co-administration of bicalutamide, mean midazolam (a CYP 3A4 substrate) levels may be increased 1.5 fold (for Cmax) and 1.9 fold (for AUC). Hence, caution should be exercised when bicalutamide is co-administered with CYP 3A4 substrates.","ncit:positive","ncit:quantitative",,"bicalutamide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","midazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","1.9","Fold","Increase","Unk","UNK","UNK","1.5","Fold","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:36:27 -0400","DDI-clinical-trial","evidence-supports","Drugs Metabolized by P450 3A4–In three separate in vivo interaction studies, sertraline was co-administered with cytochrome P450 3A4 substrates, terfenadine, carbamazepine, or cisapride under steady-state conditions. The results of these studies indicated that sertraline did not increase plasma concentrations of terfenadine, carbamazepine, or cisapride. These data indicate that sertraline’s extent of inhibition of P450 3A4 activity is not likely to be of clinical significance. Results of the interaction study with cisapride indicate that sertraline 200 mg (q.d.) induces the metabolism of cisapride (cisapride AUC and Cmax were reduced by about 35%).","ncit:negative","ncit:quantitative",,"carbamazepine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:48:50 -0400","drug-drug-interaction","evidence-supports","Teriflunomide inhibits the activity of OAT3 in vivo. In patients taking AUBAGIO, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) which are OAT3 substrates as required [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:32:33 -0500","DDI-clinical-trial","evidence-supports","Cimetidine - In subjects who had received 21 days of 40 mg/day Celexa, combined administration of 400 mg twice a day cimetidine for 8 days resulted in an increase in citalopram AUC and Cmax of 43% and 39%, respectively. ","ncit:positive","ncit:quantitative",,"cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","400","citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","40","Daily","Oral","21","BID","Oral","8","Unk","43","Percent","Increase","Unk","UNK","UNK","39","Percent","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:35:22 -0500","DDI-clinical-trial","evidence-supports","Combined administration of a single dose of ritonavir (600 mg), both a CYP3A4 substrate and a potent inhibitor of CYP3A4, and escitalopram (20 mg) did not affect the pharmacokinetics of either ritonavir or escitalopram. ","ncit:negative","ncit:quantitative",,"ritonavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","escitalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","20","UNK","Oral","Unk","UNK","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 12:50:04 -0400","drug-drug-interaction","evidence-supports","Teriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo. For a patient taking AUBAGIO, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking AUBAGIO [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","rifampin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:27:26 -0500","DDI-clinical-trial","evidence-supports","Coadministration of racemic citalopram (40 mg/day for 10 days) and lithium (30 mmol/day for 5 days) had no significant effect on the pharmacokinetics of citalopram or lithium. Nevertheless, plasma lithium levels should be monitored with appropriate adjustment to the lithium dose in accordance with standard clinical practice. Because lithium may enhance the serotonergic effects of escitalopram, caution should be exercised when Lexapro and lithium are coadministered","ncit:negative","ncit:quantitative",,"citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","40","lithium","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","30 mmol","Daily","Oral","10","Daily","IV","5","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 12:50:04 -0400","drug-drug-interaction","evidence-supports","Teriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo. For a patient taking AUBAGIO, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking AUBAGIO [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","simvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","drug-drug-interaction","evidence-supports","Teriflunomide did not affect the pharmacokinetics of bupropion (a CYP2B6 substrate), midazolam (a CYP3A4 substrate), S-warfarin (a CYP2C9 substrate), omeprazole (a CYP2C19 substrate), and metoprolol (a CYP2D6 substrate).","ncit:negative","ncit:Qualitative",,"metoprolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-09-14 11:31:14 -0400","DDI-clinical-trial","evidence-supports","In a study where propranolol (80 mg twice daily) was dosed orally for 18 days, the established steady-state plasma concentrations of propranolol were unaltered during coadministration with paroxetine (30 mg once daily) for the final 10 days. The effects of propranolol on paroxetine have not been evaluated (see ADVERSE REACTIONS: Postmarketing Reports).","ncit:negative","ncit:quantitative",,"propranolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","80","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","30","BID","Oral","18","Daily","Oral","10","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a9ff32c4-3bcf-4e51-ae8c-81ff0191ec35.html","2015-10-28 17:22:11 -0400","DDI-clinical-trial","evidence-supports","In vitro studies showed minimal inhibitory effect of desvenlafaxine on CYP2D6. Clinical studies have shown that desvenlafaxine does not have a clinically relevant effect on CYP2D6 metabolism at the dose of 100 mg daily. When desvenlafaxine succinate was administered at a dose of 100 mg daily in conjunction with a single 50 mg dose of desipramine, a CYP2D6 substrate, the Cmax and AUC of desipramine increased approximately 25% and 17%, respectively. When 400 mg (8 times the recommended 50 mg dose) was administered, the Cmax and AUC of desipramine increased approximately 50% and 90%, respectively. Concomitant use of desvenlafaxine with a drug metabolized by CYP2D6 can result in higher concentrations of that drug [see Drug Interactions (7.5)].","ncit:positive","ncit:quantitative",,"desipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","400","desvenlafaxine succinate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","SD","Oral","1","Daily","Oral","Unk","Unk","90","Percent","Increase","Unk","UNK","UNK","50","Percent","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1809bcb4-5fcc-45ca-986a-4fa5edcd4b5e.html","2015-10-29 11:26:06 -0400","drug-drug-interaction","evidence-supports","Co-administration of haloperidol with CMI increases plasma concentrations of CMI. ","ncit:positive","ncit:Qualitative",,"CMI","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction",,"haloperidol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-10-29 11:30:54 -0400","drug-drug-interaction","evidence-supports","Concurrent administration of cimetidine and tricyclic antidepressants can produce clinically significant increases in the plasma concentrations of the tricyclic antidepressants.","ncit:positive","ncit:Qualitative",,"tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1809bcb4-5fcc-45ca-986a-4fa5edcd4b5e.html","2015-09-29 09:58:27 -0400","drug-drug-interaction","evidence-supports","The plasma concentration of CMI has been reported to be increased by the concomitant administration of haloperidol; plasma levels of several closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of methylphenidate or hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by the concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin), and such an effect may be anticipated with CMI as well. Administration of CMI has been reported to increase the plasma levels of phenobarbital, if given concomitantly (see CLINICAL PHARMACOLOGY, Interactions).","ncit:positive","ncit:Qualitative",,"fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:13:55 -0400","DDI-clinical-trial","evidence-supports","Olanzapine In subjects who had received EMSAM 6 mg per 24 hours for 10 days, co-administration with olanzapine, a substrate for CYP1A2, CYP2D6, and possibly CYP2A6, did not affect the pharmacokinetics of selegiline or olanzapine [see Drug Interactions (7.4) and (7.5)].","ncit:negative","ncit:quantitative",,"olanzapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","6","UNK","UNK","Unk","Daily","transdermal","10","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","Carbamazepine-There were no clinically significant changes in the pharmacokinetics of milnacipran following co-administration of Savella (100 mg/day) and carbamazepine (200 mg twice a day). No changes were observed in the pharmacokinetics of carbamazepine or its epoxide metabolite due to co-administration with Savella. ","ncit:negative","ncit:quantitative",,"carbamazepine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","milnacipran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","200","Daily","tablet","Unk","BID","tablet","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:43:54 -0400","drug-drug-interaction","evidence-supports","Teriflunomide may be a weak inducer of CYP1A2 in vivo. In patients taking AUBAGIO, exposure of drugs metabolized by CYP1A2 (e.g., alosetron, duloxetine, theophylline, tizanidine) may be reduced. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP1A2 as required [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","theophylline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","Digoxin-There was no pharmacokinetic interaction between Savella (200 mg/day) and digoxin (0.2 mg/day Lanoxicaps) following multiple-dose administration to healthy subjects. ","ncit:negative","ncit:quantitative",,"digoxin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","0.2","Savella","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","200","Daily","tablet","Unk","Daily","tablet","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:38:35 -0500","DDI-clinical-trial","evidence-supports","Pimozide - In a controlled study, a single dose of pimozide 2 mg co-administered with citalopram 40 mg given once daily for 11 days was associated with a mean increase in QTc values of approximately 10 msec compared to pimozide given alone. Citalopram did not alter the mean AUC or Cmax of pimozide. The mechanism of this pharmacodynamic interaction is not known.","ncit:negative","ncit:quantitative",,"citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","pimozide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","2","SD","Oral","1","Daily","Oral","11","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:48:50 -0400","drug-drug-interaction","evidence-supports","Teriflunomide inhibits the activity of OAT3 in vivo. In patients taking AUBAGIO, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) which are OAT3 substrates as required [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"ciprofloxacin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c66a11c1-3093-45ef-b348-3b196c05ba0c.html","2015-10-01 10:31:02 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dosage regimen of a TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:32:33 -0500","drug-drug-interaction","evidence-supports","CYP3A4 and CYP 2C19 inhibitors: Since CYP3A4 and CYP 2C19 are the primary enzymes involved in the metabolism of citalopram, it is expected that potent inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, and macrolide antibiotics) and potent inhibitors of CYP2C19 (e.g., omeprazole) might decrease the clearance of citalopram. However, coadministration of citalopram and the potent CYP3A4 inhibitor ketoconazole did not significantly affect the pharmacokinetics of citalopram. Celexa 20 mg/day is the maximum recommended dose in patients taking concomitant cimetidine or another CYP2C19 inhibitor, because of the risk of QT prolongation (see WARNINGS and DOSAGE AND ADMINISTRATION).","ncit:negative","ncit:Qualitative",,"ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1809bcb4-5fcc-45ca-986a-4fa5edcd4b5e.html","2015-09-29 09:58:27 -0400","drug-drug-interaction","evidence-supports","The plasma concentration of CMI has been reported to be increased by the concomitant administration of haloperidol; plasma levels of several closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of methylphenidate or hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by the concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin), and such an effect may be anticipated with CMI as well. Administration of CMI has been reported to increase the plasma levels of phenobarbital, if given concomitantly (see CLINICAL PHARMACOLOGY, Interactions).","ncit:positive","ncit:Qualitative",,"barbiturates","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction","","tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-10-28 15:26:32 -0400","DDI-clinical-trial","evidence-supports","The effect of paroxetine on the pharmacokinetics of atomoxetine has been evaluated when both drugs were at steady state. In healthy volunteers who were extensive metabolizers of CYP2D6, paroxetine 20 mg daily was given in combination with 20 mg atomoxetine every 12 hours. This resulted in increases in steady state atomoxetine AUC values that were 6- to 8-fold greater and in atomoxetine Cmax values that were 3- to 4-fold greater than when atomoxetine was given alone. Dosage adjustment of atomoxetine may be necessary and it is recommended that atomoxetine be initiated at a reduced dose when it is given with paroxetine.","ncit:positive","ncit:quantitative",,"paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","atomoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","20","Q12","Oral","Unk","Daily","Oral","Unk","Unk","6-8","Fold","Increase","Unk","UNK","UNK","3-4","Fold","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:43:54 -0400","drug-drug-interaction","evidence-supports","Teriflunomide may be a weak inducer of CYP1A2 in vivo. In patients taking AUBAGIO, exposure of drugs metabolized by CYP1A2 (e.g., alosetron, duloxetine, theophylline, tizanidine) may be reduced. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP1A2 as required [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","duloxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:36:27 -0400","DDI-clinical-trial","evidence-supports","Drugs Metabolized by P450 3A4–In three separate in vivo interaction studies, sertraline was co-administered with cytochrome P450 3A4 substrates, terfenadine, carbamazepine, or cisapride under steady-state conditions. The results of these studies indicated that sertraline did not increase plasma concentrations of terfenadine, carbamazepine, or cisapride. These data indicate that sertraline’s extent of inhibition of P450 3A4 activity is not likely to be of clinical significance. Results of the interaction study with cisapride indicate that sertraline 200 mg (q.d.) induces the metabolism of cisapride (cisapride AUC and Cmax were reduced by about 35%).","ncit:negative","ncit:quantitative",,"sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","terfenadine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ea35caf8-c8c8-481a-97a2-25f68cbc240b.html","2015-09-29 09:04:36 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"propafenone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c3ca69e6-1ea0-4c2c-abcb-7264b2e79a87.html","2015-10-29 10:29:25 -0400","drug-drug-interaction","evidence-supports","Because of the pharmacologic similarity of maprotiline hydrochloride to the tricyclic antidepressants, the plasma concentration of maprotiline may be increased when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), as has occurred with tricyclic antidepressants. Adjustment of the dosage of maprotiline hydrochloride may therefore be necessary in such cases.","ncit:positive","ncit:Qualitative",,"fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"maprotiline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-10-29 11:30:54 -0400","drug-drug-interaction","evidence-supports","Certain drugs, particularly the psychostimulants and the phenothiazines, increase plasma levels of concomitantly administered tricyclic antidepressants through competition for the same metabolic enzyme systems. ","ncit:positive","ncit:Qualitative",,"psychostimulants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction",,"tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/55816042-946d-4bec-9461-bd998628ff45.html","2015-10-14 11:57:06 -0400","drug-drug-interaction","evidence-supports","Rifampin has been reported to substantially decrease the plasma concentrations of the following antiviral drugs: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir. These antiviral drugs must not be co-administered with rifampin. (See CONTRAINDICATIONS.) ","ncit:positive","ncit:Qualitative",,"darunavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Rifampin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a9ff32c4-3bcf-4e51-ae8c-81ff0191ec35.html","2015-10-28 17:22:13 -0400","DDI-clinical-trial","evidence-supports","In vitro, desvenlafaxine does not inhibit or induce the CYP3A4 isozyme. In a clinical study, desvenlafaxine 400 mg daily (8 times the recommended 50 mg dose) was co-administered with a single 4 mg dose of midazolam (a CYP3A4 substrate). The AUC and Cmax of midazolam decreased by approximately 31% and 16%, respectively. Concomitant use of desvenlafaxine with a drug metabolized by CYP3A4 can result in lower exposures to that drug. ","ncit:positive","ncit:quantitative",,"midazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","4","desvenlafaxine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","400","SD","Oral","1","Daily","Oral","Unk","Unk","31","Percent","Decrease","Unk","UNK","UNK","16","Percent","Decrease","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:48:13 -0400","DDI-clinical-trial","evidence-supports","No relevant clinical effects or significant changes in pharmacokinetics have been observed in healthy male subjects on concurrent treatment with subtherapeutic levels of lithium (600 mg/day for 10 days) at steady state and a single 30-mg dose of mirtazapine. The effects of higher doses of lithium on the pharmacokinetics of mirtazapine are unknown.","ncit:negative","ncit:quantitative",,"mirtazapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","30","lithium","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","SD","Oral","1","Daily","Oral","10","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","Fluoxetine-Switching from fluoxetine (20 mg once a day), a strong inhibitor of CYP2D6 and a moderate inhibitor of CYP2C19, to milnacipran (100 mg/day) without a washout period did not affect the pharmacokinetics of milnacipran. ","ncit:negative","ncit:quantitative",,"fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","milnacipran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","20","Daily","tablet","Unk","Daily","tablet","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-09-29 11:28:40 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type IC antiarrhythmics propafenone and flecainide). While all the SSRIs, e.g., fluoxetine, sertraline, paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","flecainide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"quinidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 14:01:28 -0500","DDI-clinical-trial","evidence-supports","Imipramine and Other Tricyclic Antidepressants (TCAs) - In vitro studies suggest that citalopram is a relatively weak inhibitor of CYP2D6. Coadministration of Celexa (40 mg/day for 10 days) with the TCA imipramine (single dose of 100 mg), a substrate for CYP2D6, did not significantly affect the plasma concentrations of imipramine or citalopram. However, the concentration of the imipramine metabolite desipramine was increased by approximately 50%. The clinical significance of the desipramine change is unknown. Nevertheless, caution is indicated in the coadministration of TCAs with Celexa.","ncit:negative","ncit:quantitative",,"Imipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","40","Daily","Oral","10","SD","Oral","1","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f356c1b-96bd-4ef1-960c-91cf4905e6b1.html","2015-09-10 14:36:47 -0400","drug-drug-interaction","evidence-supports","Anticonvulsants — Patients on stable doses of phenytoin and carbamazepine have developed elevated plasma anticonvulsant concentrations and clinical anticonvulsant toxicity following initiation of concomitant fluoxetine treatment.","ncit:positive","ncit:Qualitative",,"carbamazepine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","DDI-clinical-trial","evidence-supports","There was an increase in mean rosuvastatin Cmax and AUC (2.65- and 2.51-fold, respectively), following repeated doses of teriflunomide , suggesting that teriflunomide is an inhibitor of BCRP transporter and organic anion transporting polypeptide 1B1 and 1B3 (OATP1B1/1B3) [see Drug Interactions (7)].","ncit:positive","ncit:quantitative",,"rosuvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","2.51","Fold","Increase","Unk","UNK","UNK","2.65","Fold","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:38:24 -0400","drug-drug-interaction","evidence-supports","Teriflunomide is an inhibitor of CYP2C8 in vivo. In patients taking AUBAGIO, exposure of drugs metabolized by CYP2C8 (e.g., paclitaxel, pioglitazone, repaglinide, rosiglitazone) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP2C8 as required [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"rosiglitazone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 12:53:42 -0400","drug-drug-interaction","evidence-supports","Teriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo. For a patient taking AUBAGIO, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking AUBAGIO [see Clinical Pharmacology (12.3)]","ncit:positive","ncit:Qualitative",,"Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","rosuvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/829a4f51-c882-4b64-81f3-abfb03a52ebe.html","2015-10-29 09:30:25 -0400","DDI-clinical-trial","evidence-supports","Concomitant use of duloxetine (40 mg once daily) with paroxetine (20 mg once daily) increased the concentration of duloxetine AUC by about 60%, and greater degrees of inhibition are expected with higher doses of paroxetine. Similar effects would be expected with other potent CYP2D6 inhibitors (e.g., fluoxetine, quinidine) [see WARNINGS AND PRECAUTIONS (5.12)]. ","ncit:positive","ncit:quantitative",,"paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","duloxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","40","Daily","Oral","Unk","Daily","Oral","Unk","Unk","50","Percent","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a9ff32c4-3bcf-4e51-ae8c-81ff0191ec35.html","2015-10-28 17:17:45 -0400","DDI-clinical-trial","evidence-supports","Clinical studies have shown that desvenlafaxine (100 mg daily) does not have a clinically relevant effect on tamoxifen and aripiprazole, compounds that are metabolized by a combination of both CYP2D6 and CYP3A4 enzymes (Figure 2).","ncit:negative","ncit:quantitative",,"desvenlafaxine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","tamoxifen","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","Daily","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:43:54 -0400","drug-drug-interaction","evidence-supports","Teriflunomide may be a weak inducer of CYP1A2 in vivo. In patients taking AUBAGIO, exposure of drugs metabolized by CYP1A2 (e.g., alosetron, duloxetine, theophylline, tizanidine) may be reduced. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP1A2 as required [see Clinical Pharmacology (12.3)]","ncit:positive","ncit:Qualitative",,"Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","tizanidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:43:54 -0400","drug-drug-interaction","evidence-supports","AUBAGIO may increase the systemic exposures of ethinylestradiol and levonorgestrel. Consideration should be given to the type or dose of contraceptives used in combination with AUBAGIO [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"AUBAGIO","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","ethinylestradiol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","Pregabalin-There were no clinically significant changes in the steady-state pharmacokinetics of milnacipran or pregabalin following twice a day co-administration of 50 mg milnacipran and 150 mg pregabalin. ","ncit:negative","ncit:quantitative",,"milnacipran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","50","pregabalin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","150","BID","tablet","Unk","BID","tablet","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c66a11c1-3093-45ef-b348-3b196c05ba0c.html","2015-10-01 10:31:02 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dosage regimen of a TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","flecainide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:33:30 -0500","DDI-clinical-trial","evidence-supports","Combined administration of racemic citalopram (40 mg) and ketoconazole (200 mg), a potent CYP3A4 inhibitor, decreased the Cmax and AUC of ketoconazole by 21% and 10%, respectively, and did not significantly affect the pharmacokinetics of citalopram. ","ncit:negative","ncit:quantitative",,"citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","40","ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","UNK","Oral","Unk","UNK","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 14:00:45 -0500","DDI-clinical-trial","evidence-supports","Ketoconazole - Combined administration of Celexa (40 mg) and ketoconazole (200 mg) decreased the Cmax and AUC of ketoconazole by 21% and 10%, respectively, and did not significantly affect the pharmacokinetics of citalopram.","ncit:negative","ncit:quantitative",,"citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","40","ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","UNK","Oral","Unk","UNK","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ea35caf8-c8c8-481a-97a2-25f68cbc240b.html","2015-09-29 09:04:36 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 12:50:04 -0400","drug-drug-interaction","evidence-supports","Teriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo. For a patient taking AUBAGIO, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking AUBAGIO [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","mitoxantrone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a9ff32c4-3bcf-4e51-ae8c-81ff0191ec35.html","2015-10-28 17:17:46 -0400","DDI-clinical-trial","evidence-supports","Clinical studies have shown that desvenlafaxine (100 mg daily) does not have a clinically relevant effect on tamoxifen and aripiprazole, compounds that are metabolized by a combination of both CYP2D6 and CYP3A4 enzymes (Figure 2).","ncit:negative","ncit:quantitative",,"desvenlafaxine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","aripiprazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","Daily","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:35:24 -0400","DDI-clinical-trial","evidence-supports","In healthy male patients (n=24), carbamazepine (400 mg b.i.d.) increased mirtazapine (15 mg b.i.d.) clearance about 2-fold, resulting in a decrease in average plasma mirtazapine concentrations of 60%. When phenytoin, carbamazepine, or another inducer of hepatic metabolism (such as rifampicin) is added to mirtazapine therapy, the mirtazapine dose may have to be increased. If treatment with such a medicinal product is discontinued, it may be necessary to reduce the mirtazapine dose.","ncit:positive","ncit:quantitative",,"mirtazapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","15","carbamazepine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","400","BID","Oral","Unk","BID","Oral","Unk","24","Unk","UNK","UNK","2","Fold","Increase","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/cc9e1c8c-0e2b-44e2-878b-27057f786be9.html","2015-08-20 13:53:28 -0400","DDI-clinical-trial","evidence-supports","The blood levels of fingolimod and fingolimod-phosphate are increased by 1.7-fold when used concomitantly with ketoconazole. Patients who use GILENYA and systemic ketoconazole concomitantly should be closely monitored, as the risk of adverse reactions is greater.","ncit:positive","ncit:quantitative",,"fingolimod","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","1.7","Fold","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/7c295b64-ec39-42ec-9f02-da5b42e775e1.html","2015-08-20 10:29:59 -0400","drug-drug-interaction","evidence-supports","Clinical studies have not shown any drug interactions between bicalutamide and LHRH analogs (goserelin or leuprolide). There is no evidence that bicalutamide induces hepatic enzymes","ncit:negative","ncit:Qualitative",,"leuprolide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","bicalutamide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:35:22 -0500","DDI-clinical-trial","evidence-supports","Combined administration of a single dose of ritonavir (600 mg), both a CYP3A4 substrate and a potent inhibitor of CYP3A4, and escitalopram (20 mg) did not affect the pharmacokinetics of either ritonavir or escitalopram. ","ncit:negative","ncit:quantitative",,"escitalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","ritonavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","600","UNK","Oral","Unk","UNK","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:22:34 -0500","DDI-clinical-trial","evidence-supports","In subjects who had received 21 days of 40 mg/day racemic citalopram, combined administration of 400 mg twice a day cimetidine for 8 days resulted in an increase in citalopram AUC and Cmax of 43% and 39%, respectively. The clinical significance of these findings is unknown. ","ncit:positive","ncit:quantitative",,"cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","400","citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","40","Daily","Oral","21","BID","Oral","8","Unk","43","Percent","Increase","Unk","UNK","UNK","39","Percent","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","DDI-clinical-trial","evidence-supports","There was an increase in mean ethinylestradiol Cmax and AUC0–24 (1.58- and 1.54-fold, respectively) and levonorgestrel Cmax and AUC0–24 (1.33- and 1.41-fold, respectively) following repeated doses of teriflunomide [see Drug Interactions (7)].","ncit:positive","ncit:quantitative",,"teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","ethinylestradiol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","1.54","Fold","Increase","Unk","UNK","UNK","1.58","Fold","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-09-29 11:28:40 -0400","drug-drug-interaction","evidence-supports","Other substances, particularly barbiturates and alcohol, induce liver enzyme activity and thereby reduce tricyclic antidepressant plasma levels. Similar effects have been reported with tobacco smoke.","ncit:positive","ncit:Qualitative",,"barbiturates","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction","","tricyclic antidepressant","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a16297df-3158-48db-85e5-5cd506885556.html","2015-09-29 09:27:10 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine, cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c66a11c1-3093-45ef-b348-3b196c05ba0c.html","2015-10-29 11:36:34 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dosage regimen of a TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction",,"SSRIs","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ea35caf8-c8c8-481a-97a2-25f68cbc240b.html","2015-09-29 09:04:36 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:41:13 -0400","drug-drug-interaction","evidence-supports","In healthy, male, Caucasian patients (n=24), coadministration of the potent CYP3A4 inhibitor ketoconazole (200 mg b.i.d. for 6.5 days) increased the peak plasma levels and the AUC of a single 30-mg dose of mirtazapine by approximately 40% and 50%, respectively. Caution should be exercised when coadministering mirtazapine with potent CYP3A4 inhibitors, HIV protease inhibitors, azole antifungals, erythromycin, or nefazodone.","ncit:positive","ncit:Qualitative",,"mirtazapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"azole antifungals","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:02:39 -0500","DDI-clinical-trial","evidence-supports","In a healthy volunteer study, ritonavir 100 mg twice daily reduced the AUC and Cmax of bupropion by 22% and 21%, respectively. The exposure of the hydroxybupropion metabolite was decreased by 23%, the threohydrobupropion decreased by 38%, and the erythrohydrobupropion decreased by 48%. ","ncit:positive","ncit:quantitative",,"bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","ritonavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","UNK","UNK","Unk","BID","Oral","Unk","Unk","22","Percent","Decrease","Unk","UNK","UNK","21","Percent","Decrease","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e17dc299-f52d-414d-ab6e-e809bd6f8acb.html","2015-11-04 14:14:49 -0500","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","flecainide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","ncit:positive","ncit:Qualitative",,"Bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"metoprolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e17dc299-f52d-414d-ab6e-e809bd6f8acb.html","2015-11-04 14:14:49 -0500","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:13:14 -0500","DDI-clinical-trial","evidence-supports","In another healthy volunteer study, lopinavir 400 mg/ritonavir 100 mg twice daily decreased bupropion AUC and Cmax by 57%. The AUC and Cmax of hydroxybupropion metabolite were decreased by 50% and 31%, respectively.","ncit:positive","ncit:quantitative",,"ritonavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","hydroxybupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","BID","Oral","Unk","Unk","50","Percent","Decrease","Unk","UNK","UNK","31","Percent","Decrease","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:20:54 -0400","DDI-clinical-trial","evidence-supports","The coadministration of fluvoxamine maleate tablets and diazepam is generally not advisable. Because fluvoxamine reduces the clearance of both diazepam and its active metabolite, N-desmethyldiazepam, there is a strong likelihood of substantial accumulation of both species during chronic coadministration. Evidence supporting the conclusion that it is inadvisable to coadminister fluvoxamine and diazepam is derived from a study in which healthy volunteers taking 150 mg/day of fluvoxamine were administered a single oral dose of 10 mg of diazepam. In these subjects (N = 8), the clearance of diazepam was reduced by 65% and that of N-desmethyldiazepam to a level that was too low to measure over the course of the 2 week long study. It is likely that this experience significantly underestimates the degree of accumulation that might occur with repeated diazepam administration. Moreover, as noted with alprazolam, the effect of fluvoxamine may even be more pronounced when it is administered at higher doses. Accordingly, diazepam and fluvoxamine should not ordinarily be coadministered. ","ncit:positive","ncit:quantitative",,"N-desmethyldiazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","Unk","fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","150","UNK","UNK","Unk","Daily","Oral","Unk","8","Unk","UNK","UNK","unmeasurable","UNK","Decrease","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e17dc299-f52d-414d-ab6e-e809bd6f8acb.html","2015-11-04 14:10:24 -0500","drug-drug-interaction","evidence-challenges","Concurrent administration of cimetidine and tricyclic antidepressants can produce clinically significant increases in the plasma concentrations of the tricyclic antidepressant.","ncit:positive","ncit:Qualitative",,"cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:41:13 -0400","drug-drug-interaction","evidence-supports","In healthy, male, Caucasian patients (n=24), coadministration of the potent CYP3A4 inhibitor ketoconazole (200 mg b.i.d. for 6.5 days) increased the peak plasma levels and the AUC of a single 30-mg dose of mirtazapine by approximately 40% and 50%, respectively. Caution should be exercised when coadministering mirtazapine with potent CYP3A4 inhibitors, HIV protease inhibitors, azole antifungals, erythromycin, or nefazodone.","ncit:positive","ncit:Qualitative",,"mirtazapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"HIV protease inhibitors","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","A clinically significant fluvoxamine interaction is possible with drugs having a narrow therapeutic ratio such as pimozide, warfarin, theophylline, certain benzodiazepines, omeprazole and phenytoin. If fluvoxamine maleate tablets are to be administered together with a drug that is eliminated via oxidative metabolism and has a narrow therapeutic window, plasma levels and/or pharmacodynamic effects of the latter drug should be monitored closely, at least until steady-state conditions are reached [see Contraindications (4) and Warnings and Precautions (5)]. ","ncit:positive","ncit:Qualitative",,"fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"phenytoin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:37:50 -0500","DDI-clinical-trial","evidence-supports","When alprazolam (1 mg BID) and nefazodone (200 mg BID) were coadministered, steady-state peak concentrations, AUC and half-life values for alprazolam increased by approximately 2 fold. Nefazodone plasma concentrations were unaffected by alprazolam. If alprazolam is coadministered with nefazodone, a 50% reduction in the initial alprazolam dosage is recommended. No dosage adjustment is required for nefazodone.","ncit:positive","ncit:quantitative",,"nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","alprazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","1","SD","Oral","1","BID","Oral","Unk","Unk","2","Fold","Increase","Unk","UNK","UNK","Unk","UNK","UNK","2","Fold","Increase" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:27:20 -0500","drug-drug-interaction","evidence-supports","Ritonavir, Lopinavir, and Efavirenz: Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure. Dosage increase of WELLBUTRIN XL may be necessary when coadministered with ritonavir, lopinavir, or efavirenz but should not exceed the maximum recommended dose [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"Lopinavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"hydroxybupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 14:25:13 -0400","DDI-clinical-trial","evidence-supports","Because alosetron is metabolized by a variety of hepatic CYP drug metabolizing enzymes, inducers or inhibitors of these enzymes may change the clearance of alosetron. Fluvoxamine is a known potent inhibitor of CYP1A2 and also inhibits CYP3A4, CYP2C9, and CYP2C19. In a pharmacokinetic study, 40 healthy female subjects received fluvoxamine in escalating doses from 50 mg to 200 mg a day for 16 days, with coadministration of alosetron 1 mg on the last day. Fluvoxamine increased mean alosetron plasma concentration (AUC) approximately 6-fold and prolonged the half-life by approximately 3-fold [see Contraindications (4.1)] and Lotronex™† (alosetron) package insert. ","ncit:positive","ncit:quantitative",,"Fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","50 to 200","alosetron","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","1","SD","Oral","1","Daily","Oral","16","40","6","Fold","Increase","Unk","UNK","UNK","Unk","UNK","UNK","3","Fold","Increase" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:43:14 -0500","DDI-clinical-trial","evidence-supports","When alprazolam (1 mg BID) and nefazodone (200 mg BID) were coadministered, steady-state peak concentrations, AUC and half-life values for alprazolam increased by approximately 2 fold. Nefazodone plasma concentrations were unaffected by alprazolam. If alprazolam is coadministered with nefazodone, a 50% reduction in the initial alprazolam dosage is recommended. No dosage adjustment is required for nefazodone.","ncit:negative","ncit:quantitative",,"nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","200","alprazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","1","BID","Oral","Unk","SD","Oral","1","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:36:55 -0500","DDI-clinical-trial","evidence-supports","When a single oral 0.25 mg dose of triazolam was coadministered with nefazodone (200 mg BID) at steady state, triazolam half-life and AUC increased 4 fold and peak concentrations increased 1.7 fold. Nefazodone plasma concentrations were unaffected by triazolam. Coadministration of nefazodone potentiated the effects of triazolam on psychomotor performance tests. If triazolam is coadministered with nefazodone, a 75% reduction in the initial triazolam dosage is recommended. Because not all commercially available dosage forms of triazolam permit sufficient dosage reduction, coadministration of triazolam with nefazodone should be avoided for most patients, including the elderly. In the exceptional case where coadministration of triazolam with nefazodone may be considered appropriate, only the lowest possible dose of triazolam should be used (see CONTRAINDICATIONS and PRECAUTIONS).","ncit:positive","ncit:quantitative",,"triazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","0.25","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","SD","Oral","1","BID","Oral","Unk","Unk","4","Fold","Increase","Unk","UNK","UNK","1.7","Fold","Increase","4","Fold","Increase" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:42:05 -0500","DDI-clinical-trial","evidence-supports","In vitro studies indicate that bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists for drug interactions between WELLBUTRIN XL and drugs that are inhibitors or inducers of CYP2B6. In addition, in vitro studies suggest that paroxetine, sertraline, norfluoxetine, fluvoxamine, and nelfinavir, inhibit the hydroxylation of bupropion.","ncit:positive","ncit:quantitative",,"norfluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b8881a81-75d7-43e8-825f-37c352c146dc.html","2015-11-04 14:19:06 -0500","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics, propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction",,"cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:13:14 -0500","DDI-clinical-trial","evidence-supports","In another healthy volunteer study, lopinavir 400 mg/ritonavir 100 mg twice daily decreased bupropion AUC and Cmax by 57%. The AUC and Cmax of hydroxybupropion metabolite were decreased by 50% and 31%, respectively.","ncit:positive","ncit:quantitative","Combined lopinavir/ritonavir dose","lopinavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","400","bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","BID","Oral","Unk","Unk","57","Percent","Decrease","Unk","UNK","UNK","57","Percent","Decrease","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e17dc299-f52d-414d-ab6e-e809bd6f8acb.html","2015-11-04 14:14:49 -0500","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/0177d783-773c-41bf-9db9-eb7e5c64474a.html","2015-11-05 10:40:12 -0500","drug-drug-interaction","evidence-supports","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7-10% of caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of the isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.","ncit:positive","ncit:Qualitative",,"fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/0177d783-773c-41bf-9db9-eb7e5c64474a.html","2015-11-05 10:40:12 -0500","drug-drug-interaction","evidence-supports","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7-10% of caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of the isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.","ncit:positive","ncit:Qualitative",,"SSRIs","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction",,"tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","ncit:positive","ncit:Qualitative",,"paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","ncit:positive","ncit:Qualitative",,"Bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"flecainide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:46:57 -0500","DDI-clinical-trial","evidence-supports","Ticlopidine, Clopidogrel: In a study in healthy male volunteers, clopidogrel 75 mg once daily or ticlopidine 250 mg twice daily increased exposures (Cmax and AUC) of bupropion by 40% and 60% for clopidogrel, by 38% and 85% for ticlopidine, respectively. The exposures of hydroxybupropion were decreased. ","ncit:positive","ncit:quantitative",,"bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","clopidogrel","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","75","UNK","UNK","Unk","Daily","Oral","Unk","Unk","60","Percent","Increase","Unk","UNK","UNK","40","Percent","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:53:54 -0500","DDI-clinical-trial","evidence-supports","Cimetidine: Following oral administration of bupropion 300 mg with and without cimetidine 800 mg in 24 healthy young male volunteers, the pharmacokinetics of bupropion and hydroxybupropion were unaffected. However, there were 16% and 32% increases in the AUC and Cmax, respectively, of the combined moieties of threohydrobupropion and erythrohydrobupropion.","ncit:positive","ncit:quantitative","Combined moieties of threohydrobupropion and erythrohydrobupropion","threohydrobupropion and erythrohydrobupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","Unk","bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","800","UNK","UNK","Unk","UNK","Oral","Unk","24","16","Percent","Increase","Unk","UNK","UNK","32","Percent","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/0177d783-773c-41bf-9db9-eb7e5c64474a.html","2015-11-05 10:40:12 -0500","drug-drug-interaction","evidence-supports","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7-10% of caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of the isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.","ncit:positive","ncit:Qualitative",,"antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction",,"tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:43:14 -0500","drug-drug-interaction","evidence-supports","Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. Increased plasma concentrations of terfenadine, astemizole, cisapride, and pimozide are associated with QT prolongation and with rare cases of serious cardiovascular adverse events, including death, due principally to ventricular tachycardia of the torsade de pointes type. Nefazodone has been shown in vitro to be an inhibitor of CYP3A4. Consequently, it is recommended that nefazodone not be used in combination with either terfenadine, astemizole, cisapride, or pimozide (see CONTRAINDICATIONS and PRECAUTIONS).","ncit:positive","ncit:Qualitative",,"nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"terfenadine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:46:57 -0500","DDI-clinical-trial","evidence-supports","Ticlopidine, Clopidogrel: In a study in healthy male volunteers, clopidogrel 75 mg once daily or ticlopidine 250 mg twice daily increased exposures (Cmax and AUC) of bupropion by 40% and 60% for clopidogrel, by 38% and 85% for ticlopidine, respectively. The exposures of hydroxybupropion were decreased. ","ncit:positive","ncit:quantitative",,"ticlopidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","250","bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","BID","Oral","Unk","Unk","85","Percent","Increase","Unk","UNK","UNK","38","Percent","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","ncit:positive","ncit:Qualitative",,"Bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:29:30 -0400","DDI-clinical-trial","evidence-supports","When fluvoxamine 100 mg twice daily was administered for 3 days prior to single-dose coadministration of ramelteon 16 mg and fluvoxamine, the AUC for ramelteon increased approximately 190-fold and the Cmax increased approximately 70-fold compared to ramelteon administered alone. Ramelteon should not be used in combination with fluvoxamine. ","ncit:positive","ncit:quantitative",,"fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","ramelteon","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","16","SD","Oral","1","BID","Oral","3","Unk","190","Fold","Increase","Unk","UNK","UNK","70","Fold","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","ncit:positive","ncit:Qualitative",,"Bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"antipsychotics","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/0177d783-773c-41bf-9db9-eb7e5c64474a.html","2015-11-05 10:40:12 -0500","drug-drug-interaction","evidence-supports","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7-10% of caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of the isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.","ncit:positive","ncit:Qualitative",,"tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","propafenone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:56:02 -0500","DDI-clinical-trial","evidence-supports","Lorazepam – When lorazepam (2 mg BID) and nefazodone (200 mg BID) were coadministered to steady state, there was no change in any pharmacokinetic parameter for either drug compared to each drug administered alone. Therefore, dosage adjustment is not necessary for either drug when coadministered.","ncit:negative","ncit:quantitative",,"lorazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","2","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","200","BID","Oral","Unk","BID","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:41:13 -0400","drug-drug-interaction","evidence-supports","In healthy, male, Caucasian patients (n=24), coadministration of the potent CYP3A4 inhibitor ketoconazole (200 mg b.i.d. for 6.5 days) increased the peak plasma levels and the AUC of a single 30-mg dose of mirtazapine by approximately 40% and 50%, respectively. Caution should be exercised when coadministering mirtazapine with potent CYP3A4 inhibitors, HIV protease inhibitors, azole antifungals, erythromycin, or nefazodone.","ncit:positive","ncit:Qualitative",,"nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","mirtazapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e17dc299-f52d-414d-ab6e-e809bd6f8acb.html","2015-11-04 14:10:24 -0500","drug-drug-interaction","evidence-supports","Drugs Metabolized by P450 2D6 – The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA).","ncit:positive","ncit:Qualitative","8 fold plasma concentration increase","debrisoquin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e17dc299-f52d-414d-ab6e-e809bd6f8acb.html","2015-11-04 14:14:49 -0500","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b8881a81-75d7-43e8-825f-37c352c146dc.html","2015-11-04 14:21:12 -0500","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics, propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","Multiple hepatic cytochrome P450 isoenzymes are involved in the oxidative biotransformation of a large number of structurally different drugs and endogenous compounds. The available knowledge concerning the relationship of fluvoxamine and the cytochrome P450 isoenzyme system has been obtained mostly from pharmacokinetic interaction studies conducted in healthy volunteers, but some preliminary in vitro data are also available. Based on a finding of substantial interactions of fluvoxamine with certain of these drugs [see later parts of this section and also Warnings and Precautions (5)] and limited in vitro data for CYP3A4, it appears that fluvoxamine inhibits several cytochrome P450 isoenzymes that are known to be involved in the metabolism of other drugs such as: CYP1A2 (e.g., warfarin, theophylline, propranolol, tizanidine), CYP2C9 (e.g., warfarin), CYP3A4 (e.g., alprazolam), and CYP2C19 (e.g., omeprazole). ","ncit:positive","ncit:Qualitative",,"omeprazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:40:32 -0500","drug-drug-interaction","evidence-supports","Drugs that require metabolic activation by CYP2D6 to be effective (e.g., tamoxifen), theoretically could have reduced efficacy when administered concomitantly with inhibitors of CYP2D6 such as bupropion. Patients treated concomitantly with WELLBUTRIN XL and such drugs may require increased doses of the drug [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"tamoxifen","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:30:13 -0500","drug-drug-interaction","evidence-supports","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","ncit:positive","ncit:Qualitative",,"Bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"nortriptyline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:36:27 -0400","DDI-clinical-trial","evidence-supports","Results of a placebo-controlled trial in normal volunteers suggest that chronic administration of sertraline 200 mg/day does not produce clinically important inhibition of phenytoin metabolism. Nonetheless, at this time, it is recommended that plasma phenytoin concentrations be monitored following initiation of sertraline therapy with appropriate adjustments to the phenytoin dose, particularly in patients with multiple underlying medical conditions and/or those receiving multiple concomitant medications.","ncit:negative","ncit:quantitative",,"sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","phenytoin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:42:42 -0500","DDI-clinical-trial","evidence-supports","In vitro studies indicate that bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists for drug interactions between WELLBUTRIN XL and drugs that are inhibitors or inducers of CYP2B6. In addition, in vitro studies suggest that paroxetine, sertraline, norfluoxetine, fluvoxamine, and nelfinavir, inhibit the hydroxylation of bupropion.","ncit:positive","ncit:quantitative",,"bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:45:24 -0500","DDI-clinical-trial","evidence-supports","The coadministration of carbamazepine 200 mg BID with nefazodone 200 mg BID, at steady state for both drugs, resulted in almost 95% reductions in AUCs for nefazodone and hydroxynefazodone, likely resulting in insufficient plasma nefazodone and hydroxynefazodone concentrations for achieving an antidepressant effect for nefazodone. Consequently, it is recommended that nefazodone not be used in combination with carbamazepine (see CONTRAINDICATIONS and PRECAUTIONS).","ncit:positive","ncit:quantitative",,"nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","200","carbamazepine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","BID","Oral","Unk","BID","Oral","Unk","Unk","95","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:55:58 -0500","DDI-clinical-trial","evidence-supports"," Citalopram: Citalopram did not affect the pharmacokinetics of bupropion and its three metabolites.","ncit:negative","ncit:quantitative",,"Citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","ncit:positive","ncit:Qualitative",,"Bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"beta-blockers","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/0177d783-773c-41bf-9db9-eb7e5c64474a.html","2015-11-05 10:40:12 -0500","drug-drug-interaction","evidence-supports","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7-10% of caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of the isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.","ncit:positive","ncit:Qualitative",,"flecainide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:27:20 -0500","drug-drug-interaction","evidence-supports","Ritonavir, Lopinavir, and Efavirenz: Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure. Dosage increase of WELLBUTRIN XL may be necessary when coadministered with ritonavir, lopinavir, or efavirenz but should not exceed the maximum recommended dose [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"hydroxybupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","","ritonavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ea35caf8-c8c8-481a-97a2-25f68cbc240b.html","2015-10-29 11:11:52 -0400","drug-drug-interaction","evidence-supports","Cimetidine is reported to reduce hepatic metabolism of certain tricyclic antidepressants, thereby delaying elimination and increasing steady-state concentrations of these drugs. Clinically significant effects have been reported with the tricyclic antidepressants when used concomitantly with cimetidine. Increases in plasma levels of tricyclic antidepressants, and in the frequency and severity of side effects, particularly anticholinergic, have been reported when cimetidine was added to the drug regimen. Discontinuation of cimetidine in well controlled patients receiving tricyclic antidepressants and cimetidine may decrease the plasma levels and efficacy of the antidepressants.","ncit:positive","ncit:Qualitative",,"cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:32:38 -0400","DDI-clinical-trial","evidence-supports","When fluvoxamine maleate (50 mg t.i.d.) was administered concomitantly with warfarin for 2 weeks, warfarin plasma concentrations increased by 98% and prothrombin times were prolonged. Thus patients receiving oral anticoagulants and fluvoxamine maleate tablets should have their prothrombin time monitored and their anticoagulant dose adjusted accordingly. No dosage adjustment is required for fluvoxamine maleate tablets. ","ncit:positive","ncit:quantitative","Increased plasma concentration of warfarin","fluvoxamine maleate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","50","warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","14","TID","Oral","14","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","A clinically significant fluvoxamine interaction is possible with drugs having a narrow therapeutic ratio such as pimozide, warfarin, theophylline, certain benzodiazepines, omeprazole and phenytoin. If fluvoxamine maleate tablets are to be administered together with a drug that is eliminated via oxidative metabolism and has a narrow therapeutic window, plasma levels and/or pharmacodynamic effects of the latter drug should be monitored closely, at least until steady-state conditions are reached [see Contraindications (4) and Warnings and Precautions (5)]. ","ncit:positive","ncit:Qualitative",,"fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"benzodiazepines","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","Multiple hepatic cytochrome P450 isoenzymes are involved in the oxidative biotransformation of a large number of structurally different drugs and endogenous compounds. The available knowledge concerning the relationship of fluvoxamine and the cytochrome P450 isoenzyme system has been obtained mostly from pharmacokinetic interaction studies conducted in healthy volunteers, but some preliminary in vitro data are also available. Based on a finding of substantial interactions of fluvoxamine with certain of these drugs [see later parts of this section and also Warnings and Precautions (5)] and limited in vitro data for CYP3A4, it appears that fluvoxamine inhibits several cytochrome P450 isoenzymes that are known to be involved in the metabolism of other drugs such as: CYP1A2 (e.g., warfarin, theophylline, propranolol, tizanidine), CYP2C9 (e.g., warfarin), CYP3A4 (e.g., alprazolam), and CYP2C19 (e.g., omeprazole). ","ncit:positive","ncit:Qualitative",,"warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:29:30 -0400","drug-drug-interaction","evidence-supports","Significantly increased methadone (plasma level:dose) ratios have been reported when fluvoxamine maleate was administered to patients receiving maintenance methadone treatment, with symptoms of opioid intoxication in one patient. Opioid withdrawal symptoms were reported following fluvoxamine maleate discontinuation in another patient. ","ncit:positive","ncit:Qualitative","Increased plasma levels","fluvoxamine maleate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"methadone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:30:13 -0500","drug-drug-interaction","evidence-supports","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","ncit:positive","ncit:Qualitative",,"Bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"desipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:30:13 -0500","drug-drug-interaction","evidence-supports","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","ncit:positive","ncit:Qualitative",,"imipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:25:55 -0500","drug-drug-interaction","evidence-supports","Ritonavir, Lopinavir, and Efavirenz: Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure. Dosage increase of WELLBUTRIN XL may be necessary when coadministered with ritonavir, lopinavir, or efavirenz but should not exceed the maximum recommended dose [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Lopinavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:27:20 -0500","drug-drug-interaction","evidence-supports","Ritonavir, Lopinavir, and Efavirenz: Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure. Dosage increase of WELLBUTRIN XL may be necessary when coadministered with ritonavir, lopinavir, or efavirenz but should not exceed the maximum recommended dose [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"hydroxybupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","","Efavirenz","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:52:07 -0500","DDI-clinical-trial","evidence-supports","Cimetidine: Following oral administration of bupropion 300 mg with and without cimetidine 800 mg in 24 healthy young male volunteers, the pharmacokinetics of bupropion and hydroxybupropion were unaffected. However, there were 16% and 32% increases in the AUC and Cmax, respectively, of the combined moieties of threohydrobupropion and erythrohydrobupropion.","ncit:negative","ncit:quantitative",,"bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","300","cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","800","UNK","Oral","Unk","UNK","Oral","Unk","24","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b8881a81-75d7-43e8-825f-37c352c146dc.html","2015-11-04 14:21:12 -0500","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics, propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"propafenone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:08:54 -0500","DDI-clinical-trial","evidence-supports","In a second healthy volunteer study, ritonavir 600 mg twice daily decreased the AUC and Cmax of bupropion by 66% and 62% respectively. The exposure of the hydroxybupropion metabolite was decreased by 78%, the threohydrobupropion decreased by 50%, and the erythrohydrobupropion decreased by 68%. ","ncit:positive","ncit:quantitative","Exposure decreased by 68%","ritonavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","erythrohydrobupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","BID","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","ncit:positive","ncit:Qualitative",,"propafenone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:37:51 -0400","drug-drug-interaction","evidence-supports","Drugs Metabolized by P450 2D6–Many drugs effective in the treatment of major depressive disorder, e.g., the SSRIs, including sertraline, and most tricyclic antidepressant drugs effective in the treatment of major depressive disorder inhibit the biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase), and, thus, may increase the plasma concentrations of co-administered drugs that are metabolized by P450 2D6. The drugs for which this potential interaction is of greatest concern are those metabolized primarily by 2D6 and which have a narrow therapeutic index, e.g., the tricyclic antidepressant drugs effective in the treatment of major depressive disorder and the Type 1C antiarrhythmics propafenone and flecainide. The extent to which this interaction is an important clinical problem depends on the extent of the inhibition of P450 2D6 by the antidepressant and the therapeutic index of the co-administered drug. There is variability among the drugs effective in the treatment of major depressive disorder in the extent of clinically important 2D6 inhibition, and in fact sertraline at lower doses has a less prominent inhibitory effect on 2D6 than some others in the class. Nevertheless, even sertraline has the potential for clinically important 2D6 inhibition. Consequently, concomitant use of a drug metabolized by P450 2D6 with sertraline may require lower doses than usually prescribed for the other drug. Furthermore, whenever sertraline is withdrawn from co-therapy, an increased dose of the co-administered drug may be required (see Tricyclic Antidepressant Drugs Effective in the Treatment of Major Depressive Disorder under PRECAUTIONS).","ncit:positive","ncit:Qualitative",,"sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"flecainide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 14:27:00 -0400","drug-drug-interaction","evidence-supports","Benzodiazepines metabolized by hepatic oxidation (e.g., alprazolam, midazolam, triazolam, etc.) should be used with caution because the clearance of these drugs is likely to be reduced by fluvoxamine. ","ncit:positive","ncit:Qualitative",,"fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"alprazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:43:18 -0500","DDI-clinical-trial","evidence-supports","In vitro studies indicate that bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists for drug interactions between WELLBUTRIN XL and drugs that are inhibitors or inducers of CYP2B6. In addition, in vitro studies suggest that paroxetine, sertraline, norfluoxetine, fluvoxamine, and nelfinavir, inhibit the hydroxylation of bupropion.","ncit:positive","ncit:quantitative",,"nelfinavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 14:23:19 -0400","DDI-clinical-trial","evidence-supports","The effect of fluvoxamine (25 mg b.i.d. for one week) on thioridazine steady-state concentrations was evaluated in ten male inpatients with schizophrenia. Concentrations of thioridazine and its two active metabolites, mesoridazine and sulforidazine, increased 3-fold following coadministration of fluvoxamine. Thioridazine administration produces a dose-related prolongation of the QTc interval, which is associated with serious ventricular arrhythmias, such as torsades de pointes-type arrhythmias, and sudden death. It is likely that this experience underestimates the degree of risk that might occur with higher doses of thioridazine. Moreover, the effect of fluvoxamine may be even more pronounced when it is administered at higher doses. Therefore, fluvoxamine and thioridazine should not be coadministered [see Contraindications (4.1)]. ","ncit:positive","ncit:quantitative","3-fold concentration increase","thioridazine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","25","UNK","UNK","Unk","BID","Oral","7","10","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:08:54 -0500","DDI-clinical-trial","evidence-supports","In a second healthy volunteer study, ritonavir 600 mg twice daily decreased the AUC and Cmax of bupropion by 66% and 62% respectively. The exposure of the hydroxybupropion metabolite was decreased by 78%, the threohydrobupropion decreased by 50%, and the erythrohydrobupropion decreased by 68%. ","ncit:positive","ncit:quantitative","Exposure decreased 50%","ritonavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","threohydrobupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","BID","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/cc9e1c8c-0e2b-44e2-878b-27057f786be9.html","2015-08-20 13:57:35 -0400","drug-drug-interaction","evidence-supports","Antineoplastic, immune-modulating, or immunosuppressive therapies, (including corticosteroids) are expected to increase the risk of immunosuppression, and the risk of additive immune system effects must be considered if these therapies are coadministered with GILENYA. When switching from drugs with prolonged immune effects, such as natalizumab, teriflunomide or mitoxantrone, the duration and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects when initiating GILENYA [see Warnings and Precautions (5.2)].","ncit:positive","ncit:Qualitative",,"GILENYA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","","natalizumab","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/55816042-946d-4bec-9461-bd998628ff45.html","2015-10-14 11:57:06 -0400","drug-drug-interaction","evidence-supports","Rifampin has been reported to substantially decrease the plasma concentrations of the following antiviral drugs: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir. These antiviral drugs must not be co-administered with rifampin. (See CONTRAINDICATIONS.) ","ncit:positive","ncit:Qualitative",,"Rifampin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","atazanavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-10-29 11:30:54 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type IC antiarrhythmics propafenone and flecainide). While all the SSRIs, e.g., fluoxetine, sertraline, paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:40:46 -0400","DDI-clinical-trial","evidence-supports","Coadministration of fluvoxamine maleate 100 mg per day with atenolol 100 mg per day (N = 6) did not affect the plasma concentrations of atenolol. Unlike propranolol and metoprolol which undergo hepatic metabolism, atenolol is eliminated primarily by renal excretion. ","ncit:negative","ncit:quantitative",,"fluvoxamine maleate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","atenolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","100","Daily","Oral","Unk","Daily","Oral","Unk","6","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","Lorazepam-There was no pharmacokinetic interaction between a single dose of Savella (50 mg) and lorazepam (1.5 mg). ","ncit:negative","ncit:quantitative",,"lorazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","50","Savella","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","1.5","SD","tablet","1","SD","tablet","1","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","Digoxin-There was no pharmacokinetic interaction between Savella (200 mg/day) and digoxin (0.2 mg/day Lanoxicaps) following multiple-dose administration to healthy subjects. ","ncit:negative","ncit:quantitative",,"digoxin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","Savella","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:object-drug-of-interaction","0.2","Daily","tablet","Unk","Daily","tablet","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:13:55 -0400","DDI-clinical-trial","evidence-supports","Levothyroxine In healthy subjects who had received EMSAM 6 mg per 24 hours for 10 days, single dose administration with levothyroxine (150 mcg) did not alter the pharmacokinetics of either selegiline or levothyroxine [see Drug Interactions (7.4) and (7.5)].","ncit:negative","ncit:quantitative",,"levothyroxine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","0.15","EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","6","SD","Oral","1","Daily","transdermal","10","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","Clomipramine-Switching from clomipramine (75 mg once a day) to milnacipran (100 mg/day) without a washout period did not lead to clinically significant changes in the pharmacokinetics of milnacipran. Because an increase in adverse events (eg, euphoria and postural hypotension) was observed after switching from clomipramine to milnacipran, monitoring of patients during treatment switch is recommended. ","ncit:negative","ncit:quantitative",,"milnacipran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","75","clomipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","Daily","tablet","Unk","Daily","tablet","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a16297df-3158-48db-85e5-5cd506885556.html","2015-09-29 09:27:10 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine, cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/70b079e2-a1f7-4a93-8685-d60a4d7c1280.html","2015-10-14 12:10:56 -0400","DDI-clinical-trial","evidence-supports","CYP 2D6 inhibitors: In healthy subjects, co-administration of pimozide 2 mg (single dose) and paroxetine 60 mg resulted in a 151% increase in pimozide AUC and a 62% increase in pimozide Cmax compared to pimozide administered alone. The increase in pimozide AUC and Cmax is related to the CYP 2D6 inhibitory properties of paroxetine. Concomitant use of pimozide and paroxetine or other strong CYP 2D6 inhibitors are contraindicated (see CONTRAINDICATIONS).","ncit:positive","ncit:quantitative",,"pimozide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","2","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","60","SD","Oral","1","UNK","Oral","Unk","Unk","151","Percent","Increase","Unk","UNK","UNK","62","Percent","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:38:24 -0400","drug-drug-interaction","evidence-supports","Teriflunomide is an inhibitor of CYP2C8 in vivo. In patients taking AUBAGIO, exposure of drugs metabolized by CYP2C8 (e.g., paclitaxel, pioglitazone, repaglinide, rosiglitazone) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP2C8 as required [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"pioglitazone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c3ca69e6-1ea0-4c2c-abcb-7264b2e79a87.html","2015-10-29 10:29:25 -0400","drug-drug-interaction","evidence-supports","Because of the pharmacologic similarity of maprotiline hydrochloride to the tricyclic antidepressants, the plasma concentration of maprotiline may be increased when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), as has occurred with tricyclic antidepressants. Adjustment of the dosage of maprotiline hydrochloride may therefore be necessary in such cases.","ncit:positive","ncit:Qualitative",,"maprotiline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","maprotiline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","Lithium-Multiple doses of Savella (100 mg/day) did not affect the pharmacokinetics of lithium. ","ncit:negative","ncit:quantitative",,"Savella","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","100","lithium","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","Daily","tablet","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e338e89-3cf2-48eb-b6e2-a06c608c6513.html","2015-08-20 11:10:08 -0400","drug-drug-interaction","evidence-supports","In a dedicated drug interaction trial, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone [see Clinical Pharmacology (12.3)].","ncit:negative","ncit:Qualitative",,"ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","abiraterone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:20:54 -0400","DDI-clinical-trial","evidence-supports","The coadministration of fluvoxamine maleate tablets and diazepam is generally not advisable. Because fluvoxamine reduces the clearance of both diazepam and its active metabolite, N-desmethyldiazepam, there is a strong likelihood of substantial accumulation of both species during chronic coadministration. Evidence supporting the conclusion that it is inadvisable to coadminister fluvoxamine and diazepam is derived from a study in which healthy volunteers taking 150 mg/day of fluvoxamine were administered a single oral dose of 10 mg of diazepam. In these subjects (N = 8), the clearance of diazepam was reduced by 65% and that of N-desmethyldiazepam to a level that was too low to measure over the course of the 2 week long study. It is likely that this experience significantly underestimates the degree of accumulation that might occur with repeated diazepam administration. Moreover, as noted with alprazolam, the effect of fluvoxamine may even be more pronounced when it is administered at higher doses. Accordingly, diazepam and fluvoxamine should not ordinarily be coadministered. ","ncit:positive","ncit:quantitative",,"alprazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","10","fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","150","SD","Oral","1","Daily","Oral","UNK","8","Unk","UNK","UNK","65","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b8881a81-75d7-43e8-825f-37c352c146dc.html","2015-11-04 14:19:06 -0500","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics, propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"quinidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e17dc299-f52d-414d-ab6e-e809bd6f8acb.html","2015-11-04 14:14:49 -0500","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","quinidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:17:38 -0500","DDI-clinical-trial","evidence-supports","In vitro, bupropion and hydroxybupropion are CYP2D6 inhibitors. In a clinical study of 15 male subjects (ages 19 to 35 years) who were extensive metabolizers of CYP2D6, bupropion given as 150 mg twice daily followed by a single dose of 50 mg desipramine increased the Cmax, AUC, and T1/2 of desipramine by an average of approximately 2-, 5-, and 2-fold, respectively. The effect was present for at least 7 days after the last dose of bupropion. Concomitant use of bupropion with other drugs metabolized by CYP2D6 has not been formally studied.","ncit:positive","ncit:quantitative",,"desipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","50","bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","150","SD","Oral","1","BID","Oral","Unk","15","5","Fold","Increase","Unk","UNK","UNK","2","Fold","Increase","2","Fold","Increase" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 14:27:00 -0400","drug-drug-interaction","evidence-supports","The clearance of benzodiazepines metabolized by glucuronidation (e.g., lorazepam, oxazepam, temazepam) is unlikely to be affected by fluvoxamine. ","ncit:negative","ncit:Qualitative",,"temazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","A clinically significant fluvoxamine interaction is possible with drugs having a narrow therapeutic ratio such as pimozide, warfarin, theophylline, certain benzodiazepines, omeprazole and phenytoin. If fluvoxamine maleate tablets are to be administered together with a drug that is eliminated via oxidative metabolism and has a narrow therapeutic window, plasma levels and/or pharmacodynamic effects of the latter drug should be monitored closely, at least until steady-state conditions are reached [see Contraindications (4) and Warnings and Precautions (5)]. ","ncit:positive","ncit:Qualitative",,"pimozide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-10-28 15:25:57 -0400","DDI-clinical-trial","evidence-supports","When a single oral 30 mg dose of paroxetine was administered at phenytoin steady state (300 mg once daily for 14 days), paroxetine AUC and T½ were reduced (by an average of 50% and 35%, respectively) compared to paroxetine administered alone. In a separate study, when a single oral 300 mg dose of phenytoin was administered at paroxetine steady state (30 mg once daily for 14 days), phenytoin AUC was slightly reduced (12% on average) compared to phenytoin administered alone. Since both drugs exhibit nonlinear pharmacokinetics, the above studies may not address the case where the 2 drugs are both being chronically dosed. No initial dosage adjustments are considered necessary when these drugs are coadministered; any subsequent adjustments should be guided by clinical effect (see ADVERSE REACTIONS: Postmarketing Reports).","ncit:positive","ncit:quantitative",,"phenytoin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","300","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","30","SD","Oral","1","Daily","Oral","14","Unk","12","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","Multiple hepatic cytochrome P450 isoenzymes are involved in the oxidative biotransformation of a large number of structurally different drugs and endogenous compounds. The available knowledge concerning the relationship of fluvoxamine and the cytochrome P450 isoenzyme system has been obtained mostly from pharmacokinetic interaction studies conducted in healthy volunteers, but some preliminary in vitro data are also available. Based on a finding of substantial interactions of fluvoxamine with certain of these drugs [see later parts of this section and also Warnings and Precautions (5)] and limited in vitro data for CYP3A4, it appears that fluvoxamine inhibits several cytochrome P450 isoenzymes that are known to be involved in the metabolism of other drugs such as: CYP1A2 (e.g., warfarin, theophylline, propranolol, tizanidine), CYP2C9 (e.g., warfarin), CYP3A4 (e.g., alprazolam), and CYP2C19 (e.g., omeprazole). ","ncit:positive","ncit:Qualitative",,"theophylline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ea35caf8-c8c8-481a-97a2-25f68cbc240b.html","2015-09-29 09:04:36 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"flecainide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/55816042-946d-4bec-9461-bd998628ff45.html","2015-10-14 11:57:06 -0400","drug-drug-interaction","evidence-supports","Rifampin has been reported to substantially decrease the plasma concentrations of the following antiviral drugs: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir. These antiviral drugs must not be co-administered with rifampin. (See CONTRAINDICATIONS.) ","ncit:positive","ncit:Qualitative",,"Rifampin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","antiviral drugs","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:30:38 -0500","DDI-clinical-trial","evidence-supports","Combined administration of racemic citalopram (40 mg/day for 21 days) and the CYP1A2 substrate theophylline (single dose of 300 mg) did not affect the pharmacokinetics of theophylline. The effect of theophylline on the pharmacokinetics of citalopram was not evaluated. ","ncit:negative","ncit:quantitative",,"citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","theophylline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","3000","SD","Oral","1","Daily","Oral","21","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b8881a81-75d7-43e8-825f-37c352c146dc.html","2015-11-04 14:21:12 -0500","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics, propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"flecainide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c66a11c1-3093-45ef-b348-3b196c05ba0c.html","2015-10-01 10:31:02 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dosage regimen of a TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e17dc299-f52d-414d-ab6e-e809bd6f8acb.html","2015-11-04 14:14:49 -0500","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:33:12 -0400","DDI-clinical-trial","evidence-supports","In healthy male patients (n=18), phenytoin (200 mg daily) increased mirtazapine (30 mg daily) clearance about 2-fold, resulting in a decrease in average plasma mirtazapine concentrations of 45%. Mirtazapine did not significantly affect the pharmacokinetics of phenytoin.","ncit:negative","ncit:quantitative",,"Mirtazapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","30","phenytoin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","200","Daily","Oral","Unk","Daily","Oral","Unk","18","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/0177d783-773c-41bf-9db9-eb7e5c64474a.html","2015-11-05 10:40:12 -0500","drug-drug-interaction","evidence-supports","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7-10% of caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of the isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.","ncit:positive","ncit:Qualitative",,"paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-09-10 15:01:13 -0400","drug-drug-interaction","evidence-supports","Significantly increased plasma TCA levels have been reported with the coadministration of fluvoxamine maleate and amitriptyline, clomipramine or imipramine. Caution is indicated with the coadministration of fluvoxamine maleate tablets and TCAs; plasma TCA concentrations may need to be monitored, and the dose of TCA may need to be reduced. ","ncit:positive","ncit:Qualitative",,"amitriptyline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine maleate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 13:28:11 -0400","DDI-clinical-trial","evidence-supports","Carbamazepine Carbamazepine is an enzyme inducer and typically causes decreases in drug exposure; however, approximately 2-fold increased systemic exposure of selegiline and its metabolites, L-amphetamine and L-methamphetamine were seen after single application of EMSAM 6 mg per 24 hours in subjects who had received carbamazepine (400 mg per day) for 14 days. Changes in plasma selegiline concentrations were nearly 2-fold and variable across the subject population. Such increases may increase the risk of a hypertensive crisis when carbamazepine is used with EMSAM at any dose [see Contraindications (4), Warnings and Precautions (5.3) and Drug Interaction (7.4)].","ncit:positive","ncit:quantitative",,"L-amphetamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","Unk","carbamazepine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","6","UNK","UNK","Unk","SD","transdermal","1","Unk","2","Fold","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-10-29 11:30:54 -0400","drug-drug-interaction","evidence-supports","Certain drugs, particularly the psychostimulants and the phenothiazines, increase plasma levels of concomitantly administered tricyclic antidepressants through competition for the same metabolic enzyme systems.","ncit:positive","ncit:Qualitative",,"phenothiazines","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction","","tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:17:34 -0400","DDI-clinical-trial","evidence-supports","Risperidone In subjects who had received EMSAM 6 mg per 24 hours for 10 days, co-administration with risperidone (2 mg per day for 7 days), a substrate for CYP2D6, did not affect the pharmacokinetics of selegiline or risperidone [see Drug Interactions (7.4) and (7.5)].","ncit:negative","ncit:quantitative",,"EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:object-drug-of-interaction","6","risperidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","2","Daily","transdermal","10","Daily","Oral","7","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:39:35 -0400","DDI-clinical-trial","evidence-supports","Administration of fluvoxamine maleate 100 mg daily for 18 days (N = 8) did not significantly affect the pharmacokinetics of a 1.25 mg single intravenous dose of digoxin. ","ncit:negative","ncit:quantitative",,"digoxin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","1.25","fluvoxamine maleate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","SD","IV","1","Daily","Oral","18","8","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-10-29 11:30:54 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type IC antiarrhythmics propafenone and flecainide). While all the SSRIs, e.g., fluoxetine, sertraline, paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:22:34 -0500","DDI-clinical-trial","evidence-supports","In subjects who had received 21 days of 40 mg/day racemic citalopram, combined administration of citalopram and digoxin (single dose of 1 mg) did not significantly affect the pharmacokinetics of either citalopram or digoxin. ","ncit:negative","ncit:quantitative",,"digoxin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","1","citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","40","Daily","Oral","21","SD","Oral","1","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1809bcb4-5fcc-45ca-986a-4fa5edcd4b5e.html","2015-09-29 09:58:27 -0400","drug-drug-interaction","evidence-supports","The plasma concentration of CMI has been reported to be increased by the concomitant administration of haloperidol; plasma levels of several closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of methylphenidate or hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by the concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin), and such an effect may be anticipated with CMI as well. Administration of CMI has been reported to increase the plasma levels of phenobarbital, if given concomitantly (see CLINICAL PHARMACOLOGY, Interactions).","ncit:positive","ncit:Qualitative",,"CMI","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","haloperidol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:42:22 -0400","drug-drug-interaction","evidence-supports","No dose adjustment for EMSAM is needed when EMSAM is used concomitantly with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and CYP3A4 inhibitors (e.g., ketoconazole). No clinically meaningful change in selegiline exposure was seen when EMSAM was co-administered with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and ketoconazole [see Clinical Pharmacology (12.3)]. ","ncit:negative","ncit:Qualitative",,"olanzapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:42:22 -0400","drug-drug-interaction","evidence-supports","No dose adjustment of alprazolam, ibuprofen, levothyroxine, olanzapine, risperdione, warfarin, or strong CYP3A4 inhibitors (e.g., ketoconazole) is necessary when these drugs are used in combination with EMSAM. EMSAM had no clinically relevant effect on pharmacokinetics of these drugs.","ncit:negative","ncit:Qualitative",,"EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","","ibuprofen","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:16:45 -0400","DDI-clinical-trial","evidence-supports","Pseudoephedrine EMSAM 6 mg per 24 hours for 10 days, co-administered with pseudoephedrine (60 mg, 3 times a day) did not affect the pharmacokinetics of pseudoephedrine. There were no clinically significant changes in blood pressure during pseudoephedrine administration alone, or in combination with EMSAM [see Drug Interactions (7.4) and (7.5)]. ","ncit:negative","ncit:quantitative",,"pseudoephedrine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","60","EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","6","TID","Oral","Unk","Daily","transdermal","10","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:38:24 -0400","drug-drug-interaction","evidence-supports","AUBAGIO may increase the systemic exposures of ethinylestradiol and levonorgestrel. Consideration should be given to the type or dose of contraceptives used in combination with AUBAGIO [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"levonorgestrel","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","AUBAGIO","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-10-29 11:30:54 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type IC antiarrhythmics propafenone and flecainide). While all the SSRIs, e.g., fluoxetine, sertraline, paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction",,"cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","Multiple hepatic cytochrome P450 isoenzymes are involved in the oxidative biotransformation of a large number of structurally different drugs and endogenous compounds. The available knowledge concerning the relationship of fluvoxamine and the cytochrome P450 isoenzyme system has been obtained mostly from pharmacokinetic interaction studies conducted in healthy volunteers, but some preliminary in vitro data are also available. Based on a finding of substantial interactions of fluvoxamine with certain of these drugs [see later parts of this section and also Warnings and Precautions (5)] and limited in vitro data for CYP3A4, it appears that fluvoxamine inhibits several cytochrome P450 isoenzymes that are known to be involved in the metabolism of other drugs such as: CYP1A2 (e.g., warfarin, theophylline, propranolol, tizanidine), CYP2C9 (e.g., warfarin), CYP3A4 (e.g., alprazolam), and CYP2C19 (e.g., omeprazole). ","ncit:positive","ncit:Qualitative",,"fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"alprazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:56:02 -0500","DDI-clinical-trial","evidence-supports","Lorazepam – When lorazepam (2 mg BID) and nefazodone (200 mg BID) were coadministered to steady state, there was no change in any pharmacokinetic parameter for either drug compared to each drug administered alone. Therefore, dosage adjustment is not necessary for either drug when coadministered.","ncit:negative","ncit:quantitative",,"nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","lorazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","2","BID","Oral","Unk","BID","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:48:50 -0400","drug-drug-interaction","evidence-supports","Teriflunomide inhibits the activity of OAT3 in vivo. In patients taking AUBAGIO, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) which are OAT3 substrates as required [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"ketoprofen","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:33:30 -0500","DDI-clinical-trial","evidence-supports","Combined administration of racemic citalopram (40 mg) and ketoconazole (200 mg), a potent CYP3A4 inhibitor, decreased the Cmax and AUC of ketoconazole by 21% and 10%, respectively, and did not significantly affect the pharmacokinetics of citalopram. ","ncit:positive","ncit:quantitative",,"citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","200","UNK","Oral","Unk","UNK","Oral","Unk","Unk","21","Percent","Decrease","Unk","UNK","UNK","10","Percent","Decrease","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 12:50:04 -0400","drug-drug-interaction","evidence-supports","Teriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo. For a patient taking AUBAGIO, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking AUBAGIO [see Clinical Pharmacology (12.3)]","ncit:positive","ncit:Qualitative",,"methotrexate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b8881a81-75d7-43e8-825f-37c352c146dc.html","2015-11-04 14:19:06 -0500","drug-drug-interaction","evidence-supports","Cimetidine is reported to reduce hepatic metabolism of certain tricyclic antidepressants, thereby delaying elimination and increasing steady-state concentrations of these drugs. Clinically significant effects have been reported with the tricyclic antidepressants when used concomitantly with cimetidine. Increases in plasma levels of tricyclic antidepressants, and in the frequency and severity of side-effects, particularly anticholinergic, have been reported when cimetidine was added to the drug regimen. Discontinuation of cimetidine in well-controlled patients receiving tricyclic antidepressants and cimetidine may decrease the plasma levels and efficacy of the antidepressants.","ncit:positive","ncit:Qualitative",,"Cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:31:16 -0400","DDI-clinical-trial","evidence-supports","The effect of steady-state fluvoxamine (50 mg bid) on the pharmacokinetics of a single dose of theophylline (375 mg as 442 mg aminophylline) was evaluated in 12 healthy non-smoking, male volunteers. The clearance of theophylline was decreased approximately 3-fold. Therefore, if theophylline is coadministered with fluvoxamine maleate, its dose should be reduced to one-third of the usual daily maintenance dose and plasma concentrations of theophylline should be monitored. No dosage adjustment is required for fluvoxamine maleate tablets.","ncit:positive","ncit:quantitative",,"fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","50","theophylline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","375","SD","Oral","1","BID","Oral","Unk","12","Unk","UNK","UNK","3","Fold","Decrease","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:38:24 -0400","drug-drug-interaction","evidence-supports","Teriflunomide is an inhibitor of CYP2C8 in vivo. In patients taking AUBAGIO, exposure of drugs metabolized by CYP2C8 (e.g., paclitaxel, pioglitazone, repaglinide, rosiglitazone) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP2C8 as required [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","repaglinide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:13:01 -0400","DDI-clinical-trial","evidence-supports","Carbamazepine Carbamazepine is an enzyme inducer and typically causes decreases in drug exposure; however, approximately 2-fold increased systemic exposure of selegiline and its metabolites, L-amphetamine and L-methamphetamine were seen after single application of EMSAM 6 mg per 24 hours in subjects who had received carbamazepine (400 mg per day) for 14 days. Changes in plasma selegiline concentrations were nearly 2-fold and variable across the subject population. Such increases may increase the risk of a hypertensive crisis when carbamazepine is used with EMSAM at any dose [see Contraindications (4), Warnings and Precautions (5.3) and Drug Interaction (7.4)].","ncit:positive","ncit:quantitative",,"carbamazepine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","400","selegiline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","6","SD","transdermal","1","Daily","Oral","14","Unk","2","Fold","Increase","Unk","UNK","UNK","2","Fold","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:24:24 -0500","drug-drug-interaction","evidence-supports","Ticlopidine and Clopidogrel: Concomitant treatment with these drugs can increase bupropion exposures but decrease hydroxybupropion exposure. Based on clinical response, dosage adjustment of WELLBUTRIN XL may be necessary when coadministered with CYP2B6 inhibitors (e.g., ticlopidine or clopidogrel) [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"Ticlopidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"hydroxybupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","A clinically significant fluvoxamine interaction is possible with drugs having a narrow therapeutic ratio such as pimozide, warfarin, theophylline, certain benzodiazepines, omeprazole and phenytoin. If fluvoxamine maleate tablets are to be administered together with a drug that is eliminated via oxidative metabolism and has a narrow therapeutic window, plasma levels and/or pharmacodynamic effects of the latter drug should be monitored closely, at least until steady-state conditions are reached [see Contraindications (4) and Warnings and Precautions (5)]. ","ncit:positive","ncit:Qualitative",,"omeprazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/829a4f51-c882-4b64-81f3-abfb03a52ebe.html","2015-10-29 09:04:44 -0400","DDI-clinical-trial","evidence-supports","Under steady-state conditions for duloxetine (20 mg qhs) and temazepam (30 mg qhs), the pharmacokinetics of duloxetine were not affected by co-administration. ","ncit:negative","ncit:quantitative",,"duloxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","20","temazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","30","UNK","Oral","Unk","UNK","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:56:02 -0500","DDI-clinical-trial","evidence-supports","Haloperidol – When a single oral 5 mg dose of haloperidol was coadministered with nefazodone (200 mg BID) at steady state, haloperidol apparent clearance decreased by 35% with no significant increase in peak haloperidol plasma concentrations or time of peak. This change is of unknown clinical significance. Pharmacodynamic effects of haloperidol were generally not altered significantly. There were no changes in the pharmacokinetic parameters for nefazodone. Dosage adjustment of haloperidol may be necessary when coadministered with nefazodone.","ncit:positive","ncit:quantitative",,"haloperidol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","5","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","SD","Oral","1","BID","Oral","Unk","Unk","Unk","UNK","UNK","35","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-09-10 15:01:13 -0400","drug-drug-interaction","evidence-supports","Significantly increased plasma TCA levels have been reported with the coadministration of fluvoxamine maleate and amitriptyline, clomipramine or imipramine. Caution is indicated with the coadministration of fluvoxamine maleate tablets and TCAs; plasma TCA concentrations may need to be monitored, and the dose of TCA may need to be reduced. ","ncit:positive","ncit:Qualitative",,"fluvoxamine maleate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","clomipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:38:52 -0400","DDI-clinical-trial","evidence-supports","In healthy, male, Caucasian patients (n=24), coadministration of the potent CYP3A4 inhibitor ketoconazole (200 mg b.i.d. for 6.5 days) increased the peak plasma levels and the AUC of a single 30-mg dose of mirtazapine by approximately 40% and 50%, respectively. Caution should be exercised when coadministering mirtazapine with potent CYP3A4 inhibitors, HIV protease inhibitors, azole antifungals, erythromycin, or nefazodone.","ncit:positive","ncit:quantitative",,"mirtazapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","30","ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","SD","Oral","1","BID","Oral","6.5","24","50","Percent","Increase","Unk","UNK","UNK","40","Percent","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/829a4f51-c882-4b64-81f3-abfb03a52ebe.html","2015-10-29 09:00:42 -0400","DDI-clinical-trial","evidence-supports","Concomitant administration of duloxetine 40 mg twice daily with fluvoxamine 100 mg, a potent CYP1A2 inhibitor, to CYP2D6 poor metabolizer subjects (n=14) resulted in a 6-fold increase in duloxetine AUC and Cmax.","ncit:positive","ncit:quantitative",,"duloxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","40","fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","BID","Oral","Unk","UNK","Oral","Unk","Unk","6","Fold","Increase","Unk","UNK","UNK","6","Fold","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 14:01:03 -0500","DDI-clinical-trial","evidence-supports","Imipramine and Other Tricyclic Antidepressants (TCAs) - In vitro studies suggest that citalopram is a relatively weak inhibitor of CYP2D6. Coadministration of Celexa (40 mg/day for 10 days) with the TCA imipramine (single dose of 100 mg), a substrate for CYP2D6, did not significantly affect the plasma concentrations of imipramine or citalopram. However, the concentration of the imipramine metabolite desipramine was increased by approximately 50%. The clinical significance of the desipramine change is unknown. Nevertheless, caution is indicated in the coadministration of TCAs with Celexa.","ncit:negative","ncit:quantitative",,"citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","imipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","100","SD","Oral","1","Daily","Oral","10","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/cc9e1c8c-0e2b-44e2-878b-27057f786be9.html","2015-08-20 13:57:35 -0400","drug-drug-interaction","evidence-supports","Experience with GILENYA in patients receiving concurrent therapy with drugs that slow the heart rate or atrioventricular conduction (e.g., beta blockers, digoxin, or heart rate-slowing calcium channel blockers such as diltiazem or verapamil) is limited. Because initiation of GILENYA treatment may result in an additional decrease in heart rate, concomitant use of these drugs during GILENYA initiation may be associated with severe bradycardia or heart block. Seek advice from the prescribing physician regarding the possibility to switch to drugs that do not slow the heart rate or atrioventricular conduction before initiating GILENYA. Patients who cannot switch, should have overnight continuous ECG monitoring after the first dose [see Dosage and Administration (2) and Warnings and Precautions (5.1)]","ncit:positive","ncit:Qualitative",,"GILENYA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","","calcium channel blockers","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-09-14 11:03:10 -0400","DDI-clinical-trial","evidence-supports","When a single oral 30 mg dose of paroxetine was administered at phenytoin steady state (300 mg once daily for 14 days), paroxetine AUC and T½ were reduced (by an average of 50% and 35%, respectively) compared to paroxetine administered alone. In a separate study, when a single oral 300 mg dose of phenytoin was administered at paroxetine steady state (30 mg once daily for 14 days), phenytoin AUC was slightly reduced (12% on average) compared to phenytoin administered alone. Since both drugs exhibit nonlinear pharmacokinetics, the above studies may not address the case where the 2 drugs are both being chronically dosed. No initial dosage adjustments are considered necessary when these drugs are coadministered; any subsequent adjustments should be guided by clinical effect (see ADVERSE REACTIONS: Postmarketing Reports).","ncit:positive","ncit:quantitative",,"phenytoin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","300","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","30","SD","Oral","1","Daily","Oral","14","Unk","50","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK","35","Percent","Decrease" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","DDI-clinical-trial","evidence-supports","There was an increase in mean cefaclor Cmax and AUC (1.43- and 1.54-fold, respectively), following repeated doses of teriflunomide, suggesting that teriflunomide is an inhibitor of organic anion transporter 3 (OAT3) in vivo [see Drug Interactions (7)].","ncit:positive","ncit:quantitative",,"teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","cefaclor","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","1.54","Fold","Increase","Unk","UNK","UNK","1.43","Fold","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-09-29 11:28:40 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type IC antiarrhythmics propafenone and flecainide). While all the SSRIs, e.g., fluoxetine, sertraline, paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","phenothiazines","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:15:20 -0400","DDI-clinical-trial","evidence-supports","Olanzapine In subjects who had received EMSAM 6 mg per 24 hours for 10 days, co-administration with olanzapine, a substrate for CYP1A2, CYP2D6, and possibly CYP2A6, did not affect the pharmacokinetics of selegiline or olanzapine [see Drug Interactions (7.4) and (7.5)].","ncit:negative","ncit:quantitative",,"olanzapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:object-drug-of-interaction","6","Daily","transdermal","10","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 14:00:45 -0500","DDI-clinical-trial","evidence-supports","Imipramine and Other Tricyclic Antidepressants (TCAs) - In vitro studies suggest that citalopram is a relatively weak inhibitor of CYP2D6. Coadministration of Celexa (40 mg/day for 10 days) with the TCA imipramine (single dose of 100 mg), a substrate for CYP2D6, did not significantly affect the plasma concentrations of imipramine or citalopram. However, the concentration of the imipramine metabolite desipramine was increased by approximately 50%. The clinical significance of the desipramine change is unknown. Nevertheless, caution is indicated in the coadministration of TCAs with Celexa.","ncit:positive","ncit:quantitative",,"desipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","Unk","citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","UNK","UNK","Unk","Daily","Oral","10","Unk","Unk","UNK","UNK","Unk","UNK","UNK","50","Percent","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 13:28:11 -0400","DDI-clinical-trial","evidence-supports","Alprazolam In subjects who had received EMSAM 6 mg per 24 hours for 7 days, co-administration with alprazolam (15 mg per day), a CYP3A4 and CYP3A5 substrate, did not affect the pharmacokinetics of alprazolam or selegiline [see Drug Interactions (7.4) and (7.5)]. ","ncit:negative","ncit:quantitative",,"EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","6","alprazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","15","Daily","Oral","7","Daily","transdermal","7","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a9ff32c4-3bcf-4e51-ae8c-81ff0191ec35.html","2015-10-28 17:20:54 -0400","DDI-clinical-trial","evidence-supports","In vitro studies showed minimal inhibitory effect of desvenlafaxine on CYP2D6. Clinical studies have shown that desvenlafaxine does not have a clinically relevant effect on CYP2D6 metabolism at the dose of 100 mg daily. When desvenlafaxine succinate was administered at a dose of 100 mg daily in conjunction with a single 50 mg dose of desipramine, a CYP2D6 substrate, the Cmax and AUC of desipramine increased approximately 25% and 17%, respectively. When 400 mg (8 times the recommended 50 mg dose) was administered, the Cmax and AUC of desipramine increased approximately 50% and 90%, respectively. Concomitant use of desvenlafaxine with a drug metabolized by CYP2D6 can result in higher concentrations of that drug [see Drug Interactions (7.5)].","ncit:positive","ncit:quantitative",,"desipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","500","desvenlafaxine succinate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","SD","Oral","1","Daily","Oral","Unk","Unk","17","Percent","Increase","Unk","UNK","UNK","25","Percent","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:25:55 -0500","drug-drug-interaction","evidence-supports","Ritonavir, Lopinavir, and Efavirenz: Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure. Dosage increase of WELLBUTRIN XL may be necessary when coadministered with ritonavir, lopinavir, or efavirenz but should not exceed the maximum recommended dose [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Efavirenz","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b8881a81-75d7-43e8-825f-37c352c146dc.html","2015-11-04 14:21:12 -0500","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics, propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","phenothiazines","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/f371258d-91b3-4b6a-ac99-434a1964c3af.html","2015-10-29 09:45:11 -0400","drug-drug-interaction","evidence-supports","Concomitant use of FETZIMA with alprazolam or carbamazepine, substrates of CYP3A4, had no significant effect on alprazolam or carbamazepine plasma concentrations ","ncit:negative","ncit:Qualitative",,"carbamazepine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","FETZIMA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c3ca69e6-1ea0-4c2c-abcb-7264b2e79a87.html","2015-09-30 12:41:52 -0400","drug-drug-interaction","evidence-supports","Because of the pharmacologic similarity of maprotiline hydrochloride to the tricyclic antidepressants, the plasma concentration of maprotiline may be increased when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), as has occurred with tricyclic antidepressants. Adjustment of the dosage of maprotiline hydrochloride may therefore be necessary in such cases.","ncit:positive","ncit:Qualitative",,"maprotiline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:07:34 -0500","DDI-clinical-trial","evidence-supports","In a second healthy volunteer study, ritonavir 600 mg twice daily decreased the AUC and Cmax of bupropion by 66% and 62% respectively. The exposure of the hydroxybupropion metabolite was decreased by 78%, the threohydrobupropion decreased by 50%, and the erythrohydrobupropion decreased by 68%. ","ncit:positive","ncit:quantitative",,"bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","ritonavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","UNK","UNK","Unk","BID","Oral","Unk","Unk","66","Percent","Decrease","Unk","UNK","UNK","62","Percent","Decrease","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:35:24 -0400","DDI-clinical-trial","evidence-supports","In healthy male patients (n=12), when cimetidine, a weak inhibitor of CYP1A2, CYP2D6, and CYP3A4, given at 800 mg b.i.d. at steady state was coadministered with mirtazapine (30 mg daily) at steady state, the Area Under the Curve (AUC) of mirtazapine increased more than 50%. Mirtazapine did not cause relevant changes in the pharmacokinetics of cimetidine. The mirtazapine dose may have to be decreased when concomitant treatment with cimetidine is started, or increased when cimetidine treatment is discontinued.","ncit:negative","ncit:quantitative",,"cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","800","Mirtazapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","30","BID","Oral","Unk","Daily","Oral","Unk","12","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","drug-drug-interaction","evidence-supports","Potent CYP and transporter inducers: Rifampin did not affect the pharmacokinetics of teriflunomide.","ncit:negative","ncit:Qualitative",,"teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Rifampin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f356c1b-96bd-4ef1-960c-91cf4905e6b1.html","2015-09-10 14:36:47 -0400","drug-drug-interaction","evidence-supports","Anticonvulsants — Patients on stable doses of phenytoin and carbamazepine have developed elevated plasma anticonvulsant concentrations and clinical anticonvulsant toxicity following initiation of concomitant fluoxetine treatment. ","ncit:positive","ncit:Qualitative",,"phenytoin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/7c295b64-ec39-42ec-9f02-da5b42e775e1.html","2015-08-20 10:29:59 -0400","drug-drug-interaction","evidence-supports","Clinical studies have not shown any drug interactions between bicalutamide and LHRH analogs (goserelin or leuprolide). There is no evidence that bicalutamide induces hepatic enzymes.","ncit:negative","ncit:Qualitative",,"goserelin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","bicalutamide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1809bcb4-5fcc-45ca-986a-4fa5edcd4b5e.html","2015-10-29 11:26:06 -0400","drug-drug-interaction","evidence-supports","Co-administration of CMI with phenobarbital increases plasma concentrations of phenobarbital ","ncit:positive","ncit:Qualitative",,"CMI","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"phenobarbital","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:43:14 -0500","drug-drug-interaction","evidence-supports","Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. Increased plasma concentrations of terfenadine, astemizole, cisapride, and pimozide are associated with QT prolongation and with rare cases of serious cardiovascular adverse events, including death, due principally to ventricular tachycardia of the torsade de pointes type. Nefazodone has been shown in vitro to be an inhibitor of CYP3A4. Consequently, it is recommended that nefazodone not be used in combination with either terfenadine, astemizole, cisapride, or pimozide (see CONTRAINDICATIONS and PRECAUTIONS).","ncit:positive","ncit:Qualitative",,"nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"astemizole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c00d1607-ac36-457b-a34b-75ad74f9cf0a.html","2015-10-13 11:13:09 -0400","drug-drug-interaction","evidence-supports","The metabolism of saquinavir is mediated primarily by CYP3A. Additionally, saquinavir is a substrate for P-glycoprotein (P-gp). Therefore, drugs that affect CYP3A and/or P-gp may modify the pharmacokinetics of saquinavir. Coadministration with drugs that are potent inducers of CYP3A (e.g., phenobarbital, phenytoin, carbamazepine) may result in decreased plasma concentrations of saquinavir and reduced therapeutic effect.","ncit:positive","ncit:Qualitative",,"saquinavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","carbamazepine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c66a11c1-3093-45ef-b348-3b196c05ba0c.html","2015-10-29 11:36:34 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dosage regimen of a TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"propafenone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 11:47:01 -0400","drug-drug-interaction","evidence-supports","No dose adjustment of alprazolam, ibuprofen, levothyroxine, olanzapine, risperdione, warfarin, or strong CYP3A4 inhibitors (e.g., ketoconazole) is necessary when these drugs are used in combination with EMSAM. EMSAM had no clinically relevant effect on pharmacokinetics of these drugs.","ncit:negative","ncit:Qualitative",,"ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e338e89-3cf2-48eb-b6e2-a06c608c6513.html","2015-08-20 11:30:25 -0400","DDI-clinical-trial","evidence-supports","Abiraterone is a substrate of CYP3A4, in vitro. In a clinical pharmacokinetic interaction study of healthy subjects pretreated with a strong CYP3A4 inducer (rifampin, 600 mg daily for 6 days) followed by a single dose of abiraterone acetate 1,000 mg, the mean plasma AUC∞ of abiraterone was decreased by 55% [see Drug Interactions (7.1)].","ncit:positive","ncit:quantitative",,"abiraterone acetate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","600","rifampin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","1000","SD","UNK","1","Daily","UNK","6","Unk","55","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:56:21 -0500","DDI-clinical-trial","evidence-supports","Triazolam - Combined administration of Celexa (titrated to 40 mg/day for 28 days) and the CYP3A4 substrate triazolam (single dose of 0.25 mg) did not significantly affect the pharmacokinetics of either citalopram or triazolam.","ncit:negative","ncit:quantitative",,"Celexa","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:object-drug-of-interaction","40","triazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","0.25","Daily","Oral","28","SD","Oral","1","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:29:30 -0400","drug-drug-interaction","evidence-supports","Elevated serum levels of clozapine have been reported in patients taking fluvoxamine maleate and clozapine. Since clozapine-related seizures and orthostatic hypotension appear to be dose related, the risk of these adverse events may be higher when fluvoxamine and clozapine are coadministered. Patients should be closely monitored when fluvoxamine maleate and clozapine are used concurrently. ","ncit:positive","ncit:Qualitative",,"clozapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine maleate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 12:50:04 -0400","drug-drug-interaction","evidence-supports","Teriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo. For a patient taking AUBAGIO, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking AUBAGIO [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"nateglinide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/cc9e1c8c-0e2b-44e2-878b-27057f786be9.html","2015-08-20 13:57:35 -0400","drug-drug-interaction","evidence-supports","Antineoplastic, immune-modulating, or immunosuppressive therapies, (including corticosteroids) are expected to increase the risk of immunosuppression, and the risk of additive immune system effects must be considered if these therapies are coadministered with GILENYA. When switching from drugs with prolonged immune effects, such as natalizumab, teriflunomide or mitoxantrone, the duration and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects when initiating GILENYA [see Warnings and Precautions (5.2)].","ncit:positive","ncit:Qualitative",,"GILENYA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","","teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:46:43 -0400","DDI-clinical-trial","evidence-supports","Hypoglycemic Drugs–In a placebo-controlled trial in normal volunteers, administration of sertraline for 22 days (including 200 mg/day for the final 13 days) caused a statistically significant 16% decrease from baseline in the clearance of tolbutamide following an intravenous 1000 mg dose. Sertraline administration did not noticeably change either the plasma protein binding or the apparent volume of distribution of tolbutamide, suggesting that the decreased clearance was due to a change in the metabolism of the drug. The clinical significance of this decrease in tolbutamide clearance is unknown.","ncit:positive","ncit:quantitative",,"tolbutamide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","1000","sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","SD","IV","1","Daily","Oral","22","Unk","Unk","UNK","UNK","16","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a16297df-3158-48db-85e5-5cd506885556.html","2015-09-29 09:27:10 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine, cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"propafenone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ea35caf8-c8c8-481a-97a2-25f68cbc240b.html","2015-09-29 09:04:36 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:48:13 -0500","DDI-clinical-trial","evidence-supports","In vitro studies did not reveal an inhibitory effect of escitalopram on CYP2D6. In addition, steady state levels of racemic citalopram were not significantly different in poor metabolizers and extensive CYP2D6 metabolizers after multiple-dose administration of citalopram, suggesting that coadministration, with escitalopram, of a drug that inhibits CYP2D6, is unlikely to have clinically significant effects on escitalopram metabolism. However, there are limited in vivo data suggesting a modest CYP2D6 inhibitory effect for escitalopram, i.e., coadministration of escitalopram (20 mg/day for 21 days) with the tricyclic antidepressant desipramine (single dose of 50 mg), a substrate for CYP2D6, resulted in a 40% increase in Cmax and a 100% increase in AUC of desipramine. The clinical significance of this finding is unknown. Nevertheless, caution is indicated in the coadministration of escitalopram and drugs metabolized by CYP2D6. ","ncit:positive","ncit:quantitative",,"desipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","50","escitalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","SD","Oral","1","Daily","Oral","21","Unk","100","Percent","Increase","Unk","UNK","UNK","40","Percent","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-09-14 11:21:10 -0400","DDI-clinical-trial","evidence-supports","The steady-state pharmacokinetics of paroxetine was not altered when administered with digoxin at steady state. Mean digoxin AUC at steady state decreased by 15% in the presence of paroxetine. Since there is little clinical experience, the concurrent administration of paroxetine and digoxin should be undertaken with caution.","ncit:positive","ncit:quantitative",,"paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","digoxin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","15","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:13:01 -0400","DDI-clinical-trial","evidence-supports","Ketoconazole Seven-day treatment with ketoconazole (200 mg per day), a potent inhibitor of CYP3A4, did not affect the steady-state pharmacokinetics of selegiline in subjects who received EMSAM 6 mg per 24 hours for 7 days and no differences in the pharmacokinetics of ketoconazole were observed [see Drug Interactions (7.4) and (7.5)]. ","ncit:negative","ncit:quantitative",,"ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","selegiline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","6","Daily","transdermal","7","Daily","Oral","7","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c3ca69e6-1ea0-4c2c-abcb-7264b2e79a87.html","2015-10-29 10:29:25 -0400","drug-drug-interaction","evidence-supports","Because of the pharmacologic similarity of maprotiline hydrochloride to the tricyclic antidepressants, the plasma concentration of maprotiline may be increased when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), as has occurred with tricyclic antidepressants. Adjustment of the dosage of maprotiline hydrochloride may therefore be necessary in such cases.","ncit:positive","ncit:Qualitative",,"phenytoin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","maprotiline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 13:28:11 -0400","DDI-clinical-trial","evidence-supports","Alprazolam In subjects who had received EMSAM 6 mg per 24 hours for 7 days, co-administration with alprazolam (15 mg per day), a CYP3A4 and CYP3A5 substrate, did not affect the pharmacokinetics of alprazolam or selegiline [see Drug Interactions (7.4) and (7.5)]. ","ncit:negative","ncit:quantitative",,"alprazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","15","EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:object-drug-of-interaction","6","Daily","transdermal","7","Daily","Oral","7","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:42:22 -0400","drug-drug-interaction","evidence-supports","No dose adjustment of alprazolam, ibuprofen, levothyroxine, olanzapine, risperdione, warfarin, or strong CYP3A4 inhibitors (e.g., ketoconazole) is necessary when these drugs are used in combination with EMSAM. EMSAM had no clinically relevant effect on pharmacokinetics of these drugs.","ncit:negative","ncit:Qualitative",,"EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","","warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 12:50:04 -0400","drug-drug-interaction","evidence-supports","Teriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo. For a patient taking AUBAGIO, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking AUBAGIO [see Clinical Pharmacology (12.3)]","ncit:positive","ncit:Qualitative",,"repaglinide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:43:14 -0500","drug-drug-interaction","evidence-supports","Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. Increased plasma concentrations of terfenadine, astemizole, cisapride, and pimozide are associated with QT prolongation and with rare cases of serious cardiovascular adverse events, including death, due principally to ventricular tachycardia of the torsade de pointes type. Nefazodone has been shown in vitro to be an inhibitor of CYP3A4. Consequently, it is recommended that nefazodone not be used in combination with either terfenadine, astemizole, cisapride, or pimozide (see CONTRAINDICATIONS and PRECAUTIONS).","ncit:positive","ncit:Qualitative",,"cisapride","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:24:24 -0500","drug-drug-interaction","evidence-supports","Ticlopidine and Clopidogrel: Concomitant treatment with these drugs can increase bupropion exposures but decrease hydroxybupropion exposure. Based on clinical response, dosage adjustment of WELLBUTRIN XL may be necessary when coadministered with CYP2B6 inhibitors (e.g., ticlopidine or clopidogrel) [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Clopidogrel","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c3ca69e6-1ea0-4c2c-abcb-7264b2e79a87.html","2015-10-29 10:29:25 -0400","drug-drug-interaction","evidence-supports","Because of the pharmacologic similarity of maprotiline hydrochloride to the tricyclic antidepressants, the plasma concentration of maprotiline may be increased when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), as has occurred with tricyclic antidepressants. Adjustment of the dosage of maprotiline hydrochloride may therefore be necessary in such cases.","ncit:positive","ncit:Qualitative",,"barbiturates","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","","maprotiline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/0177d783-773c-41bf-9db9-eb7e5c64474a.html","2015-11-05 10:40:12 -0500","drug-drug-interaction","evidence-supports","There is evidence that cimetidine inhibits the elimination of tricyclic antidepressants. Downward adjustment of SURMONTIL dosage may be required if cimetidine therapy is initiated; upward adjustment if cimetidine therapy is discontinued.","ncit:positive","ncit:Qualitative",,"cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"SURMONTIL","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:43:54 -0400","drug-drug-interaction","evidence-supports","Teriflunomide may be a weak inducer of CYP1A2 in vivo. In patients taking AUBAGIO, exposure of drugs metabolized by CYP1A2 (e.g., alosetron, duloxetine, theophylline, tizanidine) may be reduced. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP1A2 as required [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","alosetron","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/f371258d-91b3-4b6a-ac99-434a1964c3af.html","2015-10-29 09:45:11 -0400","DDI-clinical-trial","evidence-supports","No dose adjustment of FETZIMA is needed when co-administered with a CYP3A4 inducer or substrate. In vivo studies showed no clinically meaningful change in levomilnacipran exposure when co-administered with the CYP3A4 inducer carbamazepine or the CYP3A4 substrate alprazolam (see Figure 1). ","ncit:negative","ncit:quantitative",,"levomilnacipran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","alprazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","phenothiazines","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:36:27 -0400","DDI-clinical-trial","evidence-supports","Drugs Metabolized by P450 3A4–In three separate in vivo interaction studies, sertraline was co-administered with cytochrome P450 3A4 substrates, terfenadine, carbamazepine, or cisapride under steady-state conditions. The results of these studies indicated that sertraline did not increase plasma concentrations of terfenadine, carbamazepine, or cisapride. These data indicate that sertraline’s extent of inhibition of P450 3A4 activity is not likely to be of clinical significance. Results of the interaction study with cisapride indicate that sertraline 200 mg (q.d.) induces the metabolism of cisapride (cisapride AUC and Cmax were reduced by about 35%).","ncit:positive","ncit:quantitative",,"cisapride","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","UNK","UNK","Unk","QD","Oral","Unk","Unk","35","Percent","Decrease","Unk","UNK","UNK","35","Percent","Decrease","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:42:22 -0400","drug-drug-interaction","evidence-supports","No dose adjustment for EMSAM is needed when EMSAM is used concomitantly with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and CYP3A4 inhibitors (e.g., ketoconazole). No clinically meaningful change in selegiline exposure was seen when EMSAM was co-administered with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and ketoconazole [see Clinical Pharmacology (12.3)]. ","ncit:negative","ncit:Qualitative",,"risperidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:42:05 -0500","DDI-clinical-trial","evidence-supports","In vitro studies indicate that bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists for drug interactions between WELLBUTRIN XL and drugs that are inhibitors or inducers of CYP2B6. In addition, in vitro studies suggest that paroxetine, sertraline, norfluoxetine, fluvoxamine, and nelfinavir, inhibit the hydroxylation of bupropion.","ncit:positive","ncit:quantitative",,"sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b8881a81-75d7-43e8-825f-37c352c146dc.html","2015-11-04 14:21:12 -0500","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics, propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:24:24 -0500","drug-drug-interaction","evidence-supports","Ticlopidine and Clopidogrel: Concomitant treatment with these drugs can increase bupropion exposures but decrease hydroxybupropion exposure. Based on clinical response, dosage adjustment of WELLBUTRIN XL may be necessary when coadministered with CYP2B6 inhibitors (e.g., ticlopidine or clopidogrel) [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"Clopidogrel","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"hydroxybupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/0177d783-773c-41bf-9db9-eb7e5c64474a.html","2015-11-05 10:40:12 -0500","drug-drug-interaction","evidence-supports","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7-10% of caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of the isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.","ncit:positive","ncit:Qualitative",,"tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:13:14 -0500","DDI-clinical-trial","evidence-supports","In another healthy volunteer study, lopinavir 400 mg/ritonavir 100 mg twice daily decreased bupropion AUC and Cmax by 57%. The AUC and Cmax of hydroxybupropion metabolite were decreased by 50% and 31%, respectively.","ncit:positive","ncit:quantitative","Combined lopinavir/ritonavir dose","bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","ritonavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","UNK","UNK","Unk","BID","Oral","Unk","Unk","57","Percent","Decrease","Unk","UNK","UNK","57","Percent","Decrease","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-09-14 11:32:07 -0400","drug-drug-interaction","evidence-supports","Coadministration of fosamprenavir/ritonavir with paroxetine significantly decreased plasma levels of paroxetine. Any dose adjustment should be guided by clinical effect (tolerability and efficacy).","ncit:positive","ncit:Qualitative",,"ritonavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/55816042-946d-4bec-9461-bd998628ff45.html","2015-10-14 11:57:06 -0400","drug-drug-interaction","evidence-supports","Rifampin has been reported to substantially decrease the plasma concentrations of the following antiviral drugs: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir. These antiviral drugs must not be co-administered with rifampin. (See CONTRAINDICATIONS.) ","ncit:positive","ncit:Qualitative",,"Rifampin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","saquinavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 13:28:11 -0400","DDI-clinical-trial","evidence-supports","Carbamazepine Carbamazepine is an enzyme inducer and typically causes decreases in drug exposure; however, approximately 2-fold increased systemic exposure of selegiline and its metabolites, L-amphetamine and L-methamphetamine were seen after single application of EMSAM 6 mg per 24 hours in subjects who had received carbamazepine (400 mg per day) for 14 days. Changes in plasma selegiline concentrations were nearly 2-fold and variable across the subject population. Such increases may increase the risk of a hypertensive crisis when carbamazepine is used with EMSAM at any dose [see Contraindications (4), Warnings and Precautions (5.3) and Drug Interaction (7.4)].","ncit:positive","ncit:quantitative",,"methamphetamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","Unk","carbamazepine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","6","UNK","UNK","Unk","SD","transdermal","1","Unk","2","Fold","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:38:36 -0400","DDI-clinical-trial","evidence-supports","In a study of 13 healthy, male volunteers, a single 40 mg dose of tacrine added to fluvoxamine 100 mg/day administered at steady-state was associated with 5- and 8-fold increases in tacrine Cmax and AUC, respectively, compared to the administration of tacrine alone. Five subjects experienced nausea, vomiting, sweating, and diarrhea following coadministration, consistent with the cholinergic effects of tacrine. ","ncit:positive","ncit:quantitative",,"fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","tacrine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","40","SD","Oral","1","Daily","Oral","Unk","13","8","Fold","Increase","Unk","UNK","UNK","5","Fold","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ea35caf8-c8c8-481a-97a2-25f68cbc240b.html","2015-09-29 09:04:36 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","phenothiazines","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","ncit:positive","ncit:Qualitative",,"Bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"risperidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/55816042-946d-4bec-9461-bd998628ff45.html","2015-10-14 11:57:06 -0400","drug-drug-interaction","evidence-supports","Rifampin has been reported to substantially decrease the plasma concentrations of the following antiviral drugs: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir. These antiviral drugs must not be co-administered with rifampin. (See CONTRAINDICATIONS.) ","ncit:positive","ncit:Qualitative",,"Rifampin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","fosamprenavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/829a4f51-c882-4b64-81f3-abfb03a52ebe.html","2015-10-29 09:24:53 -0400","DDI-clinical-trial","evidence-supports","Results of in vitro studies demonstrate that duloxetine does not inhibit activity. In a clinical study, the pharmacokinetics of S-warfarin, a CYP2C9 substrate, were not significantly affected by duloxetine [see DRUG INTERACTIONS (7.4)]. ","ncit:negative","ncit:quantitative",,"duloxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a16297df-3158-48db-85e5-5cd506885556.html","2015-09-29 09:27:10 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine, cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f356c1b-96bd-4ef1-960c-91cf4905e6b1.html","2015-09-10 14:36:47 -0400","drug-drug-interaction","evidence-supports","Antipsychotics — Some clinical data suggests a possible pharmacodynamic and/or pharmacokinetic interaction between SSRIs and antipsychotics. Elevation of blood levels of haloperidol and clozapine has been observed in patients receiving concomitant fluoxetine. ","ncit:positive","ncit:Qualitative",,"clozapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:30:38 -0500","DDI-clinical-trial","evidence-supports","In a controlled study, a single dose of pimozide 2 mg co-administered with racemic citalopram 40 mg given once daily for 11 days was associated with a mean increase in QTc values of approximately 10 msec compared to pimozide given alone. Racemic citalopram did not alter the mean AUC or Cmax of pimozide. The mechanism of this pharmacodynamic interaction is not known. ","ncit:negative","ncit:quantitative",,"pimozide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","2","citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","SD","Oral","1","Daily","Oral","11","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-10-28 15:23:30 -0400","DDI-clinical-trial","evidence-supports","Phenobarbital induces many cytochrome P450 (oxidative) enzymes. When a single oral 30 mg dose of paroxetine was administered at phenobarbital steady state (100 mg once daily for 14 days), paroxetine AUC and T½ were reduced (by an average of 25% and 38%, respectively) compared to paroxetine administered alone. The effect of paroxetine on phenobarbital pharmacokinetics was not studied. Since paroxetine exhibits nonlinear pharmacokinetics, the results of this study may not address the case where the 2 drugs are both being chronically dosed. No initial dosage adjustment of paroxetine is considered necessary when coadministered with phenobarbital; any subsequent adjustment should be guided by clinical effect.","ncit:positive","ncit:quantitative",,"paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","30","phenobarbital","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","SD","Oral","1","Daily","Oral","14","Unk","25","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK","38","Percent","Decrease" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:48:13 -0500","DDI-clinical-trial","evidence-supports","In vitro studies indicated that CYP3A4 and -2C19 are the primary enzymes involved in the metabolism of escitalopram. However, coadministration of escitalopram (20 mg) and ritonavir (600 mg), a potent inhibitor of CYP3A4, did not significantly affect the pharmacokinetics of escitalopram. Because escitalopram is metabolized by multiple enzyme systems, inhibition of a single enzyme may not appreciably decrease escitalopram clearance.","ncit:negative","ncit:quantitative",,"ritonavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","escitalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","20","UNK","Oral","Unk","UNK","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:56:02 -0500","DDI-clinical-trial","evidence-supports","Warfarin – There were no effects on the prothrombin or bleeding times or upon the pharmacokinetics of R-warfarin when nefazodone (200 mg BID) was administered for 1 week to subjects who had been pretreated for 2 weeks with warfarin. Although the coadministration of nefazodone did decrease the subjects’ exposure to S-warfarin by 12%, the lack of effects on the prothrombin and bleeding times indicates this modest change is not clinically significant. Although these results suggest no adjustments in warfarin dosage are required when nefazodone is administered to patients stabilized on warfarin, such patients should be monitored as required by standard medical practices.","ncit:negative","ncit:quantitative","12% exposure decrease","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","14","BID","Oral","7","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 14:28:56 -0400","DDI-clinical-trial","evidence-supports","When fluvoxamine maleate (100 mg q.d.) and alprazolam (1 mg q.i.d.) were coadministered to steady state, plasma concentrations and other pharmacokinetic parameters (AUC, Cmax, T½) of alprazolam were approximately twice those observed when alprazolam was administered alone; oral clearance was reduced by about 50%. The elevated plasma alprazolam concentrations resulted in decreased psychomotor performance and memory. This interaction, which has not been investigated using higher doses of fluvoxamine, may be more pronounced if a 300 mg daily dose is coadministered, particularly since fluvoxamine exhibits non-linear pharmacokinetics over the dosage range 100 mg to 300 mg. If alprazolam is coadministered with fluvoxamine maleate tablets, the initial alprazolam dosage should be at least halved and titration to the lowest effective dose is recommended. No dosage adjustment is required for fluvoxamine maleate tablets. ","ncit:positive","ncit:quantitative",,"fluvoxamine maleate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","alprazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","1","QID","Oral","Unk","QD","Oral","Unk","Unk","2","Fold","Increase","50","Percent","Decrease","2","Fold","Increase","2","Fold","Increase" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:45:24 -0500","DDI-clinical-trial","evidence-supports","The coadministration of carbamazepine 200 mg BID with nefazodone 200 mg BID, at steady state for both drugs, resulted in almost 95% reductions in AUCs for nefazodone and hydroxynefazodone, likely resulting in insufficient plasma nefazodone and hydroxynefazodone concentrations for achieving an antidepressant effect for nefazodone. Consequently, it is recommended that nefazodone not be used in combination with carbamazepine (see CONTRAINDICATIONS and PRECAUTIONS).","ncit:positive","ncit:quantitative",,"carbamazepine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","hydroxynefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","BID","Oral","Unk","Unk","95","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:52:07 -0500","DDI-clinical-trial","evidence-supports","Cimetidine: Following oral administration of bupropion 300 mg with and without cimetidine 800 mg in 24 healthy young male volunteers, the pharmacokinetics of bupropion and hydroxybupropion were unaffected. However, there were 16% and 32% increases in the AUC and Cmax, respectively, of the combined moieties of threohydrobupropion and erythrohydrobupropion.","ncit:negative","ncit:quantitative",,"cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","300","hydroxybupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","Oral","Unk","24","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:05:45 -0500","DDI-clinical-trial","evidence-supports","In a healthy volunteer study, ritonavir 100 mg twice daily reduced the AUC and Cmax of bupropion by 22% and 21%, respectively. The exposure of the hydroxybupropion metabolite was decreased by 23%, the threohydrobupropion decreased by 38%, and the erythrohydrobupropion decreased by 48%. ","ncit:positive","ncit:quantitative","Exposure decreased 48%","erythrohydrobupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","Unk","ritonavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","UNK","UNK","Unk","BID","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:04:06 -0500","DDI-clinical-trial","evidence-supports","n a healthy volunteer study, ritonavir 100 mg twice daily reduced the AUC and Cmax of bupropion by 22% and 21%, respectively. The exposure of the hydroxybupropion metabolite was decreased by 23%, the threohydrobupropion decreased by 38%, and the erythrohydrobupropion decreased by 48%. ","ncit:positive","ncit:quantitative","Exposure decreased by 23%","ritonavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","hydroxybupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","BID","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","Multiple hepatic cytochrome P450 isoenzymes are involved in the oxidative biotransformation of a large number of structurally different drugs and endogenous compounds. The available knowledge concerning the relationship of fluvoxamine and the cytochrome P450 isoenzyme system has been obtained mostly from pharmacokinetic interaction studies conducted in healthy volunteers, but some preliminary in vitro data are also available. Based on a finding of substantial interactions of fluvoxamine with certain of these drugs [see later parts of this section and also Warnings and Precautions (5)] and limited in vitro data for CYP3A4, it appears that fluvoxamine inhibits several cytochrome P450 isoenzymes that are known to be involved in the metabolism of other drugs such as: CYP1A2 (e.g., warfarin, theophylline, propranolol, tizanidine), CYP2C9 (e.g., warfarin), CYP3A4 (e.g., alprazolam), and CYP2C19 (e.g., omeprazole). ","ncit:positive","ncit:Qualitative",,"fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"propranolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-09-29 11:28:40 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type IC antiarrhythmics propafenone and flecainide). While all the SSRIs, e.g., fluoxetine, sertraline, paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-10-29 11:30:54 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type IC antiarrhythmics propafenone and flecainide). While all the SSRIs, e.g., fluoxetine, sertraline, paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction",,"propafenone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:15:31 -0500","DDI-clinical-trial","evidence-supports","Efavirenz: In a study of healthy volunteers, efavirenz 600 mg once daily for 2 weeks reduced the AUC and Cmax of bupropion by approximately 55% and 34%, respectively. The AUC of hydroxybupropion was unchanged, whereas Cmax of hydroxybupropion was increased by 50%.","ncit:positive","ncit:quantitative",,"bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","efavirenz","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","UNK","UNK","Unk","Daily","Oral","14","Unk","55","Percent","Decrease","Unk","UNK","UNK","34","Percent","Decrease","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","ncit:positive","ncit:Qualitative",,"Bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"antiarrhythmics","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:29:30 -0400","DDI-clinical-trial","evidence-supports","The effect of steady-state fluvoxamine (50 mg b.i.d. for 7 days) on the single dose pharmacokinetics of mexiletine (200 mg) was evaluated in six healthy Japanese males. The clearance of mexiletine was reduced by 38% following coadministration with fluvoxamine compared to mexiletine alone. If fluvoxamine and mexiletine are coadministered, serum mexiletine levels should be monitored. ","ncit:positive","ncit:quantitative",,"mexiletine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","200","fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","50","SD","Oral","1","BID","Oral","7","6","Unk","UNK","UNK","38","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:18:31 -0500","DDI-clinical-trial","evidence-supports","Citalopram: Although citalopram is not primarily metabolized by CYP2D6, in one study bupropion increased the Cmax and AUC of citalopram by 30% and 40%, respectively. ","ncit:positive","ncit:quantitative",,"citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","40","Percent","Increase","Unk","UNK","UNK","30","Percent","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e338e89-3cf2-48eb-b6e2-a06c608c6513.html","2015-08-20 11:10:08 -0400","DDI-clinical-trial","evidence-supports","In a CYP2C8 drug-drug interaction trial in healthy subjects, the AUC of pioglitazone (CYP2C8 substrate) was increased by 46% when pioglitazone was given together with a single dose of 1,000 mg abiraterone acetate. Therefore, patients should be monitored closely for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with ZYTIGA [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:quantitative",,"abiraterone acetate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","pioglitazone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","1000","UNK","UNK","Unk","SD","UNK","1","Unk","46","Percent","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 14:27:00 -0400","drug-drug-interaction","evidence-supports","The clearance of benzodiazepines metabolized by glucuronidation (e.g., lorazepam, oxazepam, temazepam) is unlikely to be affected by fluvoxamine. ","ncit:negative","ncit:Qualitative",,"oxazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:38:35 -0500","DDI-clinical-trial","evidence-supports","Lithium - Coadministration of Celexa (40 mg/day for 10 days) and lithium (30 mmol/day for 5 days) had no significant effect on the pharmacokinetics of citalopram or lithium. Nevertheless, plasma lithium levels should be monitored with appropriate adjustment to the lithium dose in accordance with standard clinical practice. Because lithium may enhance the serotonergic effects of citalopram, caution should be exercised when Celexa and lithium are coadministered.","ncit:negative","ncit:quantitative",,"lithium","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","30 mmol","citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","Daily","IV","5","Daily","Oral","10","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f356c1b-96bd-4ef1-960c-91cf4905e6b1.html","2015-09-10 14:36:47 -0400","drug-drug-interaction","evidence-supports","Lithium — There have been reports of both increased and decreased lithium levels when lithium was used concomitantly with fluoxetine. Cases of lithium toxicity and increased serotonergic effects have been reported. Lithium levels should be monitored when these drugs are administered concomitantly [see Warnings and Precautions (5.2)]. ","ncit:positive","ncit:Qualitative",,"fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","Lithium","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:38:35 -0500","DDI-clinical-trial","evidence-supports","Warfarin - Administration of 40 mg/day Celexa for 21 days did not affect the pharmacokinetics of warfarin, a CYP3A4 substrate. Prothrombin time was increased by 5%, the clinical significance of which is unknown.","ncit:negative","ncit:quantitative",,"Celexa","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","40","warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","Daily","Oral","21","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-10-28 15:23:30 -0400","DDI-clinical-trial","evidence-supports","Cimetidine inhibits many cytochrome P450 (oxidative) enzymes. In a study where paroxetine (30 mg once daily) was dosed orally for 4 weeks, steady-state plasma concentrations of paroxetine were increased by approximately 50% during coadministration with oral cimetidine (300 mg three times daily) for the final week. Therefore, when these drugs are administered concurrently, dosage adjustment of paroxetine after the 20 mg starting dose should be guided by clinical effect. The effect of paroxetine on cimetidine’s pharmacokinetics was not studied.","ncit:positive","ncit:quantitative",,"cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","300","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","30","Daily","Oral","28","TID","Oral","7","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","ncit:positive","ncit:Qualitative",,"Bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:38:24 -0400","drug-drug-interaction","evidence-supports","Teriflunomide is an inhibitor of CYP2C8 in vivo. In patients taking AUBAGIO, exposure of drugs metabolized by CYP2C8 (e.g., paclitaxel, pioglitazone, repaglinide, rosiglitazone) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP2C8 as required [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","paclitaxel","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-10-28 14:38:28 -0400","DDI-clinical-trial","evidence-supports","In vitro drug interaction studies reveal that paroxetine inhibits CYP2D6. Clinical drug interaction studies have been performed with substrates of CYP2D6 and show that paroxetine can inhibit the metabolism of drugs metabolized by CYP2D6 including desipramine, risperidone, and atomoxetine (see PRECAUTIONS: Drug Interactions).","ncit:positive","ncit:quantitative",,"desipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a16297df-3158-48db-85e5-5cd506885556.html","2015-09-29 09:27:10 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine, cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:49:25 -0400","DDI-clinical-trial","evidence-supports","Concomitant administration of diazepam (15 mg) had a minimal effect on plasma levels of mirtazapine (15 mg) in 12 healthy subjects. However, the impairment of motor skills produced by REMERON has been shown to be additive with those caused by diazepam. Accordingly, patients should be advised to avoid diazepam and other similar drugs while taking REMERON.","ncit:negative","ncit:quantitative",,"diazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","15","mirtazapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","15","UNK","Oral","Unk","UNK","Oral","Unk","12","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:15:20 -0400","DDI-clinical-trial","evidence-supports","Phenylpropanolamine (PPA) In subjects who had received EMSAM 6 mg per 24 hours for 9 days, co-administration with PPA (25 mg every 4 hours for 24 hours) did not affect the pharmacokinetics of PPA. There was a higher incidence of significant blood pressure elevations with the co-administration of EMSAM and PPA than with PPA alone, suggesting a possible pharmacodynamic interaction [see Drug Interactions (7.4) and (7.5)]. ","ncit:negative","ncit:quantitative","PPA given every 4 hours for 24 hours.","Phenylpropanolamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","25","EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","6","UNK","Oral","Unk","Daily","transdermal","9","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:48:13 -0400","DDI-clinical-trial","evidence-supports","In an in vivo interaction study in healthy, CYP2D6 extensive metabolizer patients (n=24), mirtazapine (30 mg/day), at steady state, did not cause relevant changes in the pharmacokinetics of steady state paroxetine (40 mg/day), a CYP2D6 inhibitor.","ncit:negative","ncit:quantitative",,"paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","40","mirtazapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","30","Daily","Oral","Unk","Daily","Oral","Unk","24","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e338e89-3cf2-48eb-b6e2-a06c608c6513.html","2015-08-20 11:17:13 -0400","DDI-clinical-trial","evidence-supports","In an in vivo drug-drug interaction trial, the Cmax and AUC of dextromethorphan (CYP2D6 substrate) were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily (plus prednisone 5 mg twice daily). The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold [see Drug Interactions (7.2)].","ncit:positive","ncit:quantitative",,"dextrorphan","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","1000","abiraterone acetate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","Daily","UNK","Unk","Unk","1.3","Fold","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c66a11c1-3093-45ef-b348-3b196c05ba0c.html","2015-10-01 10:31:02 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dosage regimen of a TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 14:00:44 -0500","DDI-clinical-trial","evidence-supports","Ketoconazole - Combined administration of Celexa (40 mg) and ketoconazole (200 mg) decreased the Cmax and AUC of ketoconazole by 21% and 10%, respectively, and did not significantly affect the pharmacokinetics of citalopram.","ncit:positive","ncit:quantitative",,"citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","200","UNK","Oral","Unk","UNK","Oral","Unk","Unk","21","Percent","Decrease","10","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:43:14 -0500","drug-drug-interaction","evidence-supports","Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. Increased plasma concentrations of terfenadine, astemizole, cisapride, and pimozide are associated with QT prolongation and with rare cases of serious cardiovascular adverse events, including death, due principally to ventricular tachycardia of the torsade de pointes type. Nefazodone has been shown in vitro to be an inhibitor of CYP3A4. Consequently, it is recommended that nefazodone not be used in combination with either terfenadine, astemizole, cisapride, or pimozide (see CONTRAINDICATIONS and PRECAUTIONS).","ncit:positive","ncit:Qualitative",,"pimozide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:30:13 -0500","drug-drug-interaction","evidence-supports","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","ncit:positive","ncit:Qualitative",,"Bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"venlafaxine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","ncit:positive","ncit:Qualitative",,"haloperidol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:48:50 -0400","drug-drug-interaction","evidence-supports","Teriflunomide inhibits the activity of OAT3 in vivo. In patients taking AUBAGIO, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) which are OAT3 substrates as required [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"cefaclor","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f356c1b-96bd-4ef1-960c-91cf4905e6b1.html","2015-11-02 16:12:40 -0500","DDI-clinical-trial","evidence-supports","Drugs Metabolized by CYP3A4 — In an in vivo interaction study involving coadministration of fluoxetine with single doses of terfenadine (a CYP3A4 substrate), no increase in plasma terfenadine concentrations occurred with concomitant fluoxetine. ","ncit:negative","ncit:quantitative",,"fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","terfenadine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","SD","UNK","1","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e17dc299-f52d-414d-ab6e-e809bd6f8acb.html","2015-11-04 14:14:49 -0500","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","ncit:positive","ncit:Qualitative",,"Bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"thioridazine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:27:26 -0500","DDI-clinical-trial","evidence-supports","Coadministration of racemic citalopram (40 mg/day for 10 days) and lithium (30 mmol/day for 5 days) had no significant effect on the pharmacokinetics of citalopram or lithium. Nevertheless, plasma lithium levels should be monitored with appropriate adjustment to the lithium dose in accordance with standard clinical practice. Because lithium may enhance the serotonergic effects of escitalopram, caution should be exercised when Lexapro and lithium are coadministered. ","ncit:negative","ncit:quantitative",,"citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","lithium","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","30 mmol","Daily","IV","5","Daily","Oral","10","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports","The plasma concentration of imipramine may increase when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decrease by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), and adjustment of the dosage of imipramine may therefore be necessary.","ncit:positive","ncit:Qualitative",,"cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","imipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:38:35 -0500","DDI-clinical-trial","evidence-supports","Theophylline - Combined administration of Celexa (40 mg/day for 21 days) and the CYP1A2 substrate theophylline (single dose of 300 mg) did not affect the pharmacokinetics of theophylline. The effect of theophylline on the pharmacokinetics of citalopram was not evaluated.","ncit:negative","ncit:quantitative",,"theophylline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","300","Celexa","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","40","SD","Oral","1","Daily","Oral","21","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1809bcb4-5fcc-45ca-986a-4fa5edcd4b5e.html","2015-09-29 11:41:50 -0400","drug-drug-interaction","evidence-supports","The plasma concentration of CMI has been reported to be increased by the concomitant administration of haloperidol; plasma levels of several closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of methylphenidate or hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by the concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin), and such an effect may be anticipated with CMI as well. Administration of CMI has been reported to increase the plasma levels of phenobarbital, if given concomitantly (see CLINICAL PHARMACOLOGY, Interactions).","ncit:positive","ncit:Qualitative",,"phenytoin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:48:50 -0400","drug-drug-interaction","evidence-supports","Teriflunomide inhibits the activity of OAT3 in vivo. In patients taking AUBAGIO, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) which are OAT3 substrates as required [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"zidovudine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:24:24 -0500","drug-drug-interaction","evidence-supports","Ticlopidine and Clopidogrel: Concomitant treatment with these drugs can increase bupropion exposures but decrease hydroxybupropion exposure. Based on clinical response, dosage adjustment of WELLBUTRIN XL may be necessary when coadministered with CYP2B6 inhibitors (e.g., ticlopidine or clopidogrel) [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Ticlopidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","DDI-clinical-trial","evidence-supports","A study of multiple doses of fluvoxamine maleate (50 mg b.i.d.) in healthy male volunteers (N = 12) and a single dose of lorazepam (4 mg single dose) indicated no significant pharmacokinetic interaction. On average, both lorazepam alone and lorazepam with fluvoxamine produced substantial decrements in cognitive functioning; however, the coadministration of fluvoxamine and lorazepam did not produce larger mean decrements compared to lorazepam alone. ","ncit:negative","ncit:quantitative",,"fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","50","lorazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","4","BID","Oral","Unk","SD","Oral","1","12","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:56:21 -0500","DDI-clinical-trial","evidence-supports","Triazolam - Combined administration of Celexa (titrated to 40 mg/day for 28 days) and the CYP3A4 substrate triazolam (single dose of 0.25 mg) did not significantly affect the pharmacokinetics of either citalopram or triazolam.","ncit:negative","ncit:quantitative",,"citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","triazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","0.25","SD","Oral","1","Daily","Oral","28","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports","The plasma concentration of imipramine may increase when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decrease by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), and adjustment of the dosage of imipramine may therefore be necessary.","ncit:positive","ncit:Qualitative",,"imipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","barbiturates","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-09-14 11:31:14 -0400","drug-drug-interaction","evidence-supports","Under steady-state conditions, diazepam does not appear to affect paroxetine kinetics. The effects of paroxetine on diazepam were not evaluated.","ncit:negative","ncit:Qualitative",,"paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","diazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","DDI-clinical-trial","evidence-supports","Repeated doses of teriflunomide decreased mean Cmax and AUC of caffeine by 18% and 55%, respectively, suggesting that teriflunomide may be a weak inducer of CYP1A2 in vivo.","ncit:positive","ncit:quantitative",,"caffeine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","55","Percent","Increase","Unk","UNK","UNK","18","Percent","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:42:22 -0400","drug-drug-interaction","evidence-supports","No dose adjustment for EMSAM is needed when EMSAM is used concomitantly with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and CYP3A4 inhibitors (e.g., ketoconazole). No clinically meaningful change in selegiline exposure was seen when EMSAM was co-administered with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and ketoconazole [see Clinical Pharmacology (12.3)]. ","ncit:negative","ncit:Qualitative",,"levothyroxine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:32:33 -0500","DDI-clinical-trial","evidence-supports","Combined administration of racemic citalopram (titrated to 40 mg/day for 28 days) and the CYP3A4 substrate triazolam (single dose of 0.25 mg) did not significantly affect the pharmacokinetics of either citalopram or triazolam.","ncit:negative","ncit:quantitative",,"citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","40","triazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","0.25","Daily","Oral","28","SD","Oral","1","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:21:18 -0500","DDI-clinical-trial","evidence-supports"," Lamotrigine: Multiple oral doses of bupropion had no statistically significant effects on the single-dose pharmacokinetics of lamotrigine in 12 healthy volunteers.","ncit:negative","ncit:quantitative",,"lamotrigine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","SD","Oral","1","UNK","Oral","Unk","12","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","A clinically significant fluvoxamine interaction is possible with drugs having a narrow therapeutic ratio such as pimozide, warfarin, theophylline, certain benzodiazepines, omeprazole and phenytoin. If fluvoxamine maleate tablets are to be administered together with a drug that is eliminated via oxidative metabolism and has a narrow therapeutic window, plasma levels and/or pharmacodynamic effects of the latter drug should be monitored closely, at least until steady-state conditions are reached [see Contraindications (4) and Warnings and Precautions (5)]. ","ncit:positive","ncit:Qualitative",,"theophylline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:42:22 -0400","drug-drug-interaction","evidence-supports","No dose adjustment of alprazolam, ibuprofen, levothyroxine, olanzapine, risperdione, warfarin, or strong CYP3A4 inhibitors (e.g., ketoconazole) is necessary when these drugs are used in combination with EMSAM. EMSAM had no clinically relevant effect on pharmacokinetics of these drugs.","ncit:negative","ncit:Qualitative",,"EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","","risperdione","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 12:50:04 -0400","drug-drug-interaction","evidence-supports","Teriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo. For a patient taking AUBAGIO, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking AUBAGIO [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"rosuvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 12:50:04 -0400","drug-drug-interaction","evidence-supports","Teriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo. For a patient taking AUBAGIO, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking AUBAGIO [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"atorvastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:36:27 -0400","DDI-clinical-trial","evidence-supports","n a controlled study of a single dose (2 mg) of pimozide, 200 mg sertraline (q.d.) co-administration to steady state was associated with a mean increase in pimozide AUC and Cmax of about 40%, but was not associated with any changes in EKG. Since the highest recommended pimozide dose (10 mg) has not been evaluated in combination with sertraline, the effect on QT interval and PK parameters at doses higher than 2 mg at this time are not known. While the mechanism of this interaction is unknown, due to the narrow therapeutic index of pimozide and due to the interaction noted at a low dose of pimozide, concomitant administration of sertraline and pimozide should be contraindicated (see ","ncit:positive","ncit:quantitative",,"sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","pimozide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","2","SD","Oral","1","QD","Oral","Unk","Unk","40","Percent","Increase","Unk","UNK","UNK","40","Percent","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:42:22 -0400","drug-drug-interaction","evidence-supports","No dose adjustment for EMSAM is needed when EMSAM is used concomitantly with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and CYP3A4 inhibitors (e.g., ketoconazole). No clinically meaningful change in selegiline exposure was seen when EMSAM was co-administered with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and ketoconazole [see Clinical Pharmacology (12.3)]. ","ncit:negative","ncit:Qualitative",,"EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","","ibuprofen","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","drug-drug-interaction","evidence-supports","Teriflunomide did not affect the pharmacokinetics of bupropion (a CYP2B6 substrate), midazolam (a CYP3A4 substrate), S-warfarin (a CYP2C9 substrate), omeprazole (a CYP2C19 substrate), and metoprolol (a CYP2D6 substrate).","ncit:negative","ncit:Qualitative",,"Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","omeprazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:41:13 -0400","drug-drug-interaction","evidence-supports","In healthy, male, Caucasian patients (n=24), coadministration of the potent CYP3A4 inhibitor ketoconazole (200 mg b.i.d. for 6.5 days) increased the peak plasma levels and the AUC of a single 30-mg dose of mirtazapine by approximately 40% and 50%, respectively. Caution should be exercised when coadministering mirtazapine with potent CYP3A4 inhibitors, HIV protease inhibitors, azole antifungals, erythromycin, or nefazodone.","ncit:positive","ncit:Qualitative",,"erythromycin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","mirtazapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:34:44 -0500","DDI-clinical-trial","evidence-supports","The coadministration of triazolam and nefazodone causes a significant increase in the plasma level of triazolam (see WARNINGS and PRECAUTIONS), and a 75% reduction in the initial triazolam dosage is recommended if the two drugs are to be given together. Because not all commercially available dosage forms of triazolam permit a sufficient dosage reduction, the coadministration of triazolam and nefazodone should be avoided for most patients, including the elderly.","ncit:positive","ncit:quantitative","Increased plasma level","nefazodone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","triazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","Warfarin-Steady-state milnacipran (200 mg/day) did not affect the pharmacokinetics of R-warfarin and S-warfarin or the pharmacodynamics (as assessed by measurement of prothrombin INR) of a single dose of 25 mg warfarin. The pharmacokinetics of Savella were not altered by warfarin. ","ncit:negative","ncit:quantitative",,"Savella","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:object-drug-of-interaction","25","warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","Daily","tablet","Unk","SD","tablet","1","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-09-14 11:21:10 -0400","drug-drug-interaction","evidence-supports","A multiple-dose study has shown that there is no pharmacokinetic interaction between paroxetine and lithium carbonate. However, due to the potential for serotonin syndrome, caution is advised when paroxetine is coadministered with lithium.","ncit:negative","ncit:Qualitative",,"paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","lithium carbonate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","ncit:positive","ncit:Qualitative",,"fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/f371258d-91b3-4b6a-ac99-434a1964c3af.html","2015-10-29 09:45:11 -0400","DDI-clinical-trial","evidence-supports","Dose adjustment is recommended when FETZIMA is co-administered with strong inhibitors of CYP3A4 (e.g. ketoconazole) [see Dosage and Administration (2.7)]. An in vivo study showed a clinically meaningful increase in levomilnacipran exposure when FETZIMA was co-administered with the CYP3A4 inhibitor ketoconazole (see Figure 1). ","ncit:positive","ncit:quantitative",,"ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","levomilnacipran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c00d1607-ac36-457b-a34b-75ad74f9cf0a.html","2015-10-13 11:13:09 -0400","drug-drug-interaction","evidence-supports","The metabolism of saquinavir is mediated primarily by CYP3A. Additionally, saquinavir is a substrate for P-glycoprotein (P-gp). Therefore, drugs that affect CYP3A and/or P-gp may modify the pharmacokinetics of saquinavir. Coadministration with drugs that are potent inducers of CYP3A (e.g., phenobarbital, phenytoin, carbamazepine) may result in decreased plasma concentrations of saquinavir and reduced therapeutic effect.","ncit:positive","ncit:Qualitative",,"saquinavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","phenytoin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:42:22 -0400","drug-drug-interaction","evidence-supports","No dose adjustment for EMSAM is needed when EMSAM is used concomitantly with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and CYP3A4 inhibitors (e.g., ketoconazole). No clinically meaningful change in selegiline exposure was seen when EMSAM was co-administered with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and ketoconazole [see Clinical Pharmacology (12.3)]. ","ncit:negative","ncit:Qualitative",,"EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","","alprazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/0177d783-773c-41bf-9db9-eb7e5c64474a.html","2015-11-05 10:40:12 -0500","drug-drug-interaction","evidence-supports","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7-10% of caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of the isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.","ncit:positive","ncit:Qualitative",,"tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 14:27:00 -0400","drug-drug-interaction","evidence-supports","Benzodiazepines metabolized by hepatic oxidation (e.g., alprazolam, midazolam, triazolam, etc.) should be used with caution because the clearance of these drugs is likely to be reduced by fluvoxamine. ","ncit:positive","ncit:Qualitative",,"fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"triazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","drug-drug-interaction","evidence-supports","Teriflunomide did not affect the pharmacokinetics of bupropion (a CYP2B6 substrate), midazolam (a CYP3A4 substrate), S-warfarin (a CYP2C9 substrate), omeprazole (a CYP2C19 substrate), and metoprolol (a CYP2D6 substrate).","ncit:negative","ncit:Qualitative",,"midazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:25:55 -0500","drug-drug-interaction","evidence-supports","Ritonavir, Lopinavir, and Efavirenz: Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure. Dosage increase of WELLBUTRIN XL may be necessary when coadministered with ritonavir, lopinavir, or efavirenz but should not exceed the maximum recommended dose [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:Qualitative",,"bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","ritonavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-10-28 15:25:57 -0400","DDI-clinical-trial","evidence-supports","Concomitant use of paroxetine with risperidone, a CYP2D6 substrate has also been evaluated. In 1 study, daily dosing of paroxetine 20 mg in patients stabilized on risperidone (4 to 8 mg/day) increased mean plasma concentrations of risperidone approximately 4-fold, decreased 9-hydroxyrisperidone concentrations approximately 10%, and increased concentrations of the active moiety (the sum of risperidone plus 9-hydroxyrisperidone) approximately 1.4-fold.","ncit:positive","ncit:quantitative",,"paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","9-hydroxyrisperidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","Daily","Oral","Unk","Unk","10","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","drug-drug-interaction","evidence-supports","Teriflunomide did not affect the pharmacokinetics of bupropion (a CYP2B6 substrate), midazolam (a CYP3A4 substrate), S-warfarin (a CYP2C9 substrate), omeprazole (a CYP2C19 substrate), and metoprolol (a CYP2D6 substrate).","ncit:negative","ncit:Qualitative",,"Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/829a4f51-c882-4b64-81f3-abfb03a52ebe.html","2015-10-29 09:30:04 -0400","DDI-clinical-trial","evidence-supports","Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies of the case-control and cohort design that have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding have also shown that concurrent use of an NSAID or aspirin may potentiate this risk of bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs or SNRIs are co-administered with warfarin. Concomitant administration of warfarin (2 to 9 mg once daily) under steady state conditions with duloxetine 60 or 120 mg once daily for up to 14 days in healthy subjects (n=15) did not significantly change INR from baseline (mean INR changes ranged from 0.05 to +0.07). The total warfarin (protein bound plus free drug) pharmacokinetics (AUCτ,ss, Cmax,ss or tmax,ss) for both R- and S-warfarin were not altered by duloxetine. Because of the potential effect of duloxetine on platelets, patients receiving warfarin therapy should be carefully monitored when duloxetine is initiated or discontinued [see WARNINGS AND PRECAUTIONS (5.5)]. ","ncit:negative","ncit:quantitative",,"duloxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","60 or 120","warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","2 to 9","Daily","UNK","Unk","Daily","Oral","14","15","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:48:28 -0500","DDI-clinical-trial","evidence-supports","Prasugrel: In healthy subjects, prasugrel increased bupropion Cmax and AUC values by 14% and 18%, respectively, and decreased Cmax and AUC values of hydroxybupropion by 32% and 24%, respectively.","ncit:positive","ncit:quantitative",,"prasugrel","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","18","Percent","Increase","Unk","UNK","UNK","14","Percent","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:40:32 -0500","DDI-clinical-trial","evidence-supports","In vitro studies indicate that bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists for drug interactions between WELLBUTRIN XL and drugs that are inhibitors or inducers of CYP2B6. In addition, in vitro studies suggest that paroxetine, sertraline, norfluoxetine, fluvoxamine, and nelfinavir, inhibit the hydroxylation of bupropion.","ncit:positive","ncit:quantitative",,"bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:36:26 -0400","DDI-clinical-trial","evidence-supports","In a study comparing the disposition of intravenously administered diazepam before and after 21 days of dosing with either sertraline (50 to 200 mg/day escalating dose) or placebo, there was a 32% decrease relative to baseline in diazepam clearance for the sertraline group compared to a 19% decrease relative to baseline for the placebo group (p < 0.03). There was a 23% increase in Tmax for desmethyldiazepam in the sertraline group compared to a 20% decrease in the placebo group (p < 0.03). The clinical significance of these changes is unknown.","ncit:positive","ncit:quantitative",,"sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","50-200","diazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","IV","Unk","Daily","Oral","21","Unk","Unk","UNK","UNK","32","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c66a11c1-3093-45ef-b348-3b196c05ba0c.html","2015-10-01 10:31:02 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dosage regimen of a TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"quinidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports","The plasma concentration of imipramine may increase when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decrease by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), and adjustment of the dosage of imipramine may therefore be necessary.","ncit:positive","ncit:Qualitative",,"phenytoin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","imipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/70b079e2-a1f7-4a93-8685-d60a4d7c1280.html","2015-10-14 12:07:40 -0400","DDI-clinical-trial","evidence-supports","Pimozide and Celexa: In a controlled study, a single dose of pimozide 2 mg coadministered with racemic citalopram 40 mg given once daily for 11 days was associated with a mean increase in QTc values of approximately 10 msec compared to pimozide given alone. Racemic citalopram did not alter the mean AUC or Cmax of pimozide. The mechanism of this pharmacodynamic interaction is not known. Concomitant use of Pimozide and Celexa or Lexapro is contraindicated (See CONTRAINDICATIONS).","ncit:negative","ncit:quantitative",,"citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","pimozide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","2","SD","Oral","1","Daily","Oral","11","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a9ff32c4-3bcf-4e51-ae8c-81ff0191ec35.html","2015-10-28 17:20:12 -0400","DDI-clinical-trial","evidence-supports","CYP3A4 is a minor pathway for the metabolism of desvenlafaxine. In a clinical study, ketoconazole (200 mg BID) increased the area under the concentration vs. time curve (AUC) of desvenlafaxine (400 mg single dose) by about 43% and Cmax by about 8%. Concomitant use of desvenlafaxine with potent inhibitors of CYP3A4 may result in higher concentrations of desvenlafaxine. ","ncit:positive","ncit:quantitative",,"desvenlafaxine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","400","ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","SD","Oral","1","BID","Oral","Unk","Unk","43","Percent","Increase","Unk","UNK","UNK","8","Percent","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-10-28 14:38:28 -0400","DDI-clinical-trial","evidence-supports","In vitro drug interaction studies reveal that paroxetine inhibits CYP2D6. Clinical drug interaction studies have been performed with substrates of CYP2D6 and show that paroxetine can inhibit the metabolism of drugs metabolized by CYP2D6 including desipramine, risperidone, and atomoxetine (see PRECAUTIONS: Drug Interactions).","ncit:positive","ncit:quantitative",,"risperidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/0177d783-773c-41bf-9db9-eb7e5c64474a.html","2015-11-05 10:40:12 -0500","drug-drug-interaction","evidence-supports","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7-10% of caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of the isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.","ncit:positive","ncit:Qualitative",,"tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction",,"quinidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 14:23:19 -0400","DDI-clinical-trial","evidence-supports","Fluvoxamine is a potent inhibitor of CYP1A2 and tizanidine is a CYP1A2 substrate. The effect of fluvoxamine (100 mg daily for 4 days) on the pharmacokinetics and pharmacodynamics of a single 4 mg dose of tizanidine has been studied in ten healthy male subjects. Tizanidine Cmax was increased approximately 12-fold (range 5-fold to 32-fold), elimination half-life was increased by almost 3-fold, and AUC increased 33-fold (range 14-fold to 103-fold). The mean maximal effect on blood pressure was a 35 mm Hg decrease in systolic blood pressure, a 20 mm Hg decrease in diastolic blood pressure, and a 4 beat/min decrease in heart rate. Drowsiness was significantly increased and performance on the psychomotor task was significantly impaired. Fluvoxamine and tizanidine should not be used together [see Contraindications (4.1)].","ncit:positive","ncit:quantitative",,"tizanidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","4","Fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","SD","Oral","1","Daily","Oral","4","10","33","Fold","Increase","Unk","UNK","UNK","12","Fold","Increase","3","Fold","Increase" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/cc9e1c8c-0e2b-44e2-878b-27057f786be9.html","2015-08-20 13:57:35 -0400","drug-drug-interaction","evidence-supports","Antineoplastic, immune-modulating, or immunosuppressive therapies, (including corticosteroids) are expected to increase the risk of immunosuppression, and the risk of additive immune system effects must be considered if these therapies are coadministered with GILENYA. When switching from drugs with prolonged immune effects, such as natalizumab, teriflunomide or mitoxantrone, the duration and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects when initiating GILENYA [see Warnings and Precautions (5.2)].","ncit:positive","ncit:Qualitative",,"mitoxantrone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","GILENYA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:42:22 -0400","drug-drug-interaction","evidence-supports","No dose adjustment of alprazolam, ibuprofen, levothyroxine, olanzapine, risperdione, warfarin, or strong CYP3A4 inhibitors (e.g., ketoconazole) is necessary when these drugs are used in combination with EMSAM. EMSAM had no clinically relevant effect on pharmacokinetics of these drugs.","ncit:negative","ncit:Qualitative",,"levothyroxine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:38:35 -0500","DDI-clinical-trial","evidence-supports","Lithium - Coadministration of Celexa (40 mg/day for 10 days) and lithium (30 mmol/day for 5 days) had no significant effect on the pharmacokinetics of citalopram or lithium. Nevertheless, plasma lithium levels should be monitored with appropriate adjustment to the lithium dose in accordance with standard clinical practice. Because lithium may enhance the serotonergic effects of citalopram, caution should be exercised when Celexa and lithium are coadministered.","ncit:negative","ncit:quantitative",,"lithium","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","30 mmol","citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","40","Daily","Oral","10","Daily","IV","5","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/829a4f51-c882-4b64-81f3-abfb03a52ebe.html","2015-10-29 09:04:02 -0400","DDI-clinical-trial","evidence-supports","Under steady-state conditions for duloxetine (60 mg Q 12 hours) and lorazepam (2 mg Q 12 hours), the pharmacokinetics of duloxetine were not affected by co-administration. ","ncit:negative","ncit:quantitative",,"lorazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","2","duloxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","60","Q12",,"Unk","Q12","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","drug-drug-interaction","evidence-supports","Teriflunomide did not affect the pharmacokinetics of bupropion (a CYP2B6 substrate), midazolam (a CYP3A4 substrate), S-warfarin (a CYP2C9 substrate), omeprazole (a CYP2C19 substrate), and metoprolol (a CYP2D6 substrate).","ncit:negative","ncit:Qualitative",,"Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","bupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","Approximately 7% of the normal population has a genetic code that leads to reduced levels of activity of CYP2D6. Such individuals have been referred to as “poor metabolizers” (PM) of drugs such as debrisoquin, dextromethorphan, and tricyclic antidepressants. While none of the drugs studied for drug interactions significantly affected the pharmacokinetics of fluvoxamine, an in vivo study of fluvoxamine single-dose pharmacokinetics in 13 PM subjects demonstrated altered pharmacokinetic properties compared to 16 “extensive metabolizers” (EM): mean Cmax, AUC, and half-life were increased by 52%, 200%, and 62%, respectively, in the PM compared to the EM group. This suggests that fluvoxamine is metabolized, at least in part, by CYP2D6. Caution is indicated in patients known to have reduced levels of CYP2D6 activity and those receiving concomitant drugs known to inhibit this cytochrome P450 isoenzyme (e.g., quinidine). ","ncit:positive","ncit:Qualitative",,"fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"quinidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c00d1607-ac36-457b-a34b-75ad74f9cf0a.html","2015-10-13 11:13:09 -0400","drug-drug-interaction","evidence-supports","The metabolism of saquinavir is mediated primarily by CYP3A. Additionally, saquinavir is a substrate for P-glycoprotein (P-gp). Therefore, drugs that affect CYP3A and/or P-gp may modify the pharmacokinetics of saquinavir. Coadministration with drugs that are potent inducers of CYP3A (e.g., phenobarbital, phenytoin, carbamazepine) may result in decreased plasma concentrations of saquinavir and reduced therapeutic effect.","ncit:positive","ncit:Qualitative",,"phenobarbital","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","saquinavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b8881a81-75d7-43e8-825f-37c352c146dc.html","2015-11-04 14:19:06 -0500","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics, propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction",,"antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","Multiple hepatic cytochrome P450 isoenzymes are involved in the oxidative biotransformation of a large number of structurally different drugs and endogenous compounds. The available knowledge concerning the relationship of fluvoxamine and the cytochrome P450 isoenzyme system has been obtained mostly from pharmacokinetic interaction studies conducted in healthy volunteers, but some preliminary in vitro data are also available. Based on a finding of substantial interactions of fluvoxamine with certain of these drugs [see later parts of this section and also Warnings and Precautions (5)] and limited in vitro data for CYP3A4, it appears that fluvoxamine inhibits several cytochrome P450 isoenzymes that are known to be involved in the metabolism of other drugs such as: CYP1A2 (e.g., warfarin, theophylline, propranolol, tizanidine), CYP2C9 (e.g., warfarin), CYP3A4 (e.g., alprazolam), and CYP2C19 (e.g., omeprazole). ","ncit:positive","ncit:Qualitative",,"tizanidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","DDI-clinical-trial","evidence-supports","There was an increase in mean ethinylestradiol Cmax and AUC0–24 (1.58- and 1.54-fold, respectively) and levonorgestrel Cmax and AUC0–24 (1.33- and 1.41-fold, respectively) following repeated doses of teriflunomide [see Drug Interactions (7)].","ncit:positive","ncit:quantitative",,"teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","levonorgestrel","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","1.41","Fold","Increase","Unk","UNK","UNK","1.33","Fold","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-09-14 11:21:10 -0400","DDI-clinical-trial","evidence-supports","Concomitant use of paroxetine with risperidone, a CYP2D6 substrate has also been evaluated. In 1 study, daily dosing of paroxetine 20 mg in patients stabilized on risperidone (4 to 8 mg/day) increased mean plasma concentrations of risperidone approximately 4-fold, decreased 9-hydroxyrisperidone concentrations approximately 10%, and increased concentrations of the active moiety (the sum of risperidone plus 9-hydroxyrisperidone) approximately 1.4-fold.","ncit:positive","ncit:quantitative",,"paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","risperidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","4-8","Daily","Oral","Unk","Daily","Oral","Unk","Unk","4","Fold","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:13:01 -0400","DDI-clinical-trial","evidence-supports","Ibuprofen In subjects who had received EMSAM 6 mg per 24 hours for 11 days, combined administration with the CYP2C9 substrate ibuprofen (800 mg single dose) did not affect the pharmacokinetics of either selegiline or ibuprofen [see Drug Interactions (7.4) and (7.5)]. ","ncit:negative","ncit:quantitative",,"EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","6","ibuprofen","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","800","SD","Oral","1","Daily","transdermal","11","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1809bcb4-5fcc-45ca-986a-4fa5edcd4b5e.html","2015-09-29 09:58:27 -0400","drug-drug-interaction","evidence-supports","The plasma concentration of CMI has been reported to be increased by the concomitant administration of haloperidol; plasma levels of several closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of methylphenidate or hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by the concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin), and such an effect may be anticipated with CMI as well. Administration of CMI has been reported to increase the plasma levels of phenobarbital, if given concomitantly (see CLINICAL PHARMACOLOGY, Interactions).","ncit:positive","ncit:Qualitative",,"tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","methylphenidate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/cc9e1c8c-0e2b-44e2-878b-27057f786be9.html","2015-08-20 13:57:35 -0400","drug-drug-interaction","evidence-supports","Experience with GILENYA in patients receiving concurrent therapy with drugs that slow the heart rate or atrioventricular conduction (e.g., beta blockers, digoxin, or heart rate-slowing calcium channel blockers such as diltiazem or verapamil) is limited. Because initiation of GILENYA treatment may result in an additional decrease in heart rate, concomitant use of these drugs during GILENYA initiation may be associated with severe bradycardia or heart block. Seek advice from the prescribing physician regarding the possibility to switch to drugs that do not slow the heart rate or atrioventricular conduction before initiating GILENYA. Patients who cannot switch, should have overnight continuous ECG monitoring after the first dose [see Dosage and Administration (2) and Warnings and Precautions (5.1)].","ncit:positive","ncit:Qualitative",,"diltiazem","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","GILENYA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:35:24 -0400","DDI-clinical-trial","evidence-supports","In healthy male patients (n=12), when cimetidine, a weak inhibitor of CYP1A2, CYP2D6, and CYP3A4, given at 800 mg b.i.d. at steady state was coadministered with mirtazapine (30 mg daily) at steady state, the Area Under the Curve (AUC) of mirtazapine increased more than 50%. Mirtazapine did not cause relevant changes in the pharmacokinetics of cimetidine. The mirtazapine dose may have to be decreased when concomitant treatment with cimetidine is started, or increased when cimetidine treatment is discontinued.","ncit:positive","ncit:quantitative",,"cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","800","mirtazapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","30","Daily","Oral","Unk","BID","Oral","Unk","12","50","Percent","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","SSRIs","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-09-29 11:28:40 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type IC antiarrhythmics propafenone and flecainide). While all the SSRIs, e.g., fluoxetine, sertraline, paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","SSRIs","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:30:38 -0500","DDI-clinical-trial","evidence-supports","Administration of 40 mg/day racemic citalopram for 21 days did not affect the pharmacokinetics of warfarin, a CYP3A4 substrate. Prothrombin time was increased by 5%, the clinical significance of which is unknown. ","ncit:negative","ncit:quantitative",,"citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","Daily","Oral","21","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-10-28 15:25:57 -0400","DDI-clinical-trial","evidence-supports","Many drugs, including most drugs effective in the treatment of major depressive disorder (paroxetine, other SSRIs and many tricyclics), are metabolized by the cytochrome P450 isozyme CYP2D6. Like other agents that are metabolized by CYP2D6, paroxetine may significantly inhibit the activity of this isozyme. In most patients (>90%), this CYP2D6 isozyme is saturated early during dosing with paroxetine. In 1 study, daily dosing of paroxetine (20 mg once daily) under steady-state conditions increased single dose desipramine (100 mg) Cmax, AUC, and T½ by an average of approximately 2-, 5-, and 3-fold, respectively. ","ncit:positive","ncit:quantitative",,"paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","desipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","100","SD","Oral","Unk","Daily","Oral","Unk","Unk","5","Fold","Increase","Unk","UNK","UNK","2","Fold","Increase","3","Fold","Increase" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e338e89-3cf2-48eb-b6e2-a06c608c6513.html","2015-08-20 11:32:27 -0400","drug-drug-interaction","evidence-supports","In a separate clinical pharmacokinetic interaction study of healthy subjects, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone [see Drug Interactions (7.1)].","ncit:negative","ncit:Qualitative",,"abiraterone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:42:22 -0400","drug-drug-interaction","evidence-supports","No dose adjustment of alprazolam, ibuprofen, levothyroxine, olanzapine, risperdione, warfarin, or strong CYP3A4 inhibitors (e.g., ketoconazole) is necessary when these drugs are used in combination with EMSAM. EMSAM had no clinically relevant effect on pharmacokinetics of these drugs. ","ncit:negative","ncit:Qualitative",,"EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","","alprazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/829a4f51-c882-4b64-81f3-abfb03a52ebe.html","2015-10-29 09:10:04 -0400","DDI-clinical-trial","evidence-supports","In vitro drug interaction studies demonstrate that duloxetine does not induce CYP1A2 activity. Therefore, an increase in the metabolism of CYP1A2 substrates (e.g., theophylline, caffeine) resulting from induction is not anticipated, although clinical studies of induction have not been performed. Duloxetine is an inhibitor of the CYP1A2 isoform in in vitro studies, and in two clinical studies the average (90% confidence interval) increase in theophylline AUC was 7% (1% to 15%) and 20% (13% to 27%) when co-administered with duloxetine (60 mg twice daily). ","ncit:positive","ncit:quantitative",,"theophylline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","duloxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","60","UNK","UNK","Unk","BID","Oral","Unk","Unk","7-20","Percent","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:13:14 -0500","DDI-clinical-trial","evidence-supports","In another healthy volunteer study, lopinavir 400 mg/ritonavir 100 mg twice daily decreased bupropion AUC and Cmax by 57%. The AUC and Cmax of hydroxybupropion metabolite were decreased by 50% and 31%, respectively.","ncit:positive","ncit:quantitative",,"hydroxybupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","lopinavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","400","UNK","UNK","Unk","BID","Oral","Unk","Unk","50","Percent","Decrease","Unk","UNK","UNK","31","Percent","Decrease","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e17dc299-f52d-414d-ab6e-e809bd6f8acb.html","2015-11-04 14:14:49 -0500","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"propafenone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e17dc299-f52d-414d-ab6e-e809bd6f8acb.html","2015-11-04 14:14:49 -0500","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","phenothiazines","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:38:04 -0400","drug-drug-interaction","evidence-supports","Elevated carbamazepine levels and symptoms of toxicity have been reported with the coadministration of fluvoxamine maleate and carbamazepine. ","ncit:positive","ncit:Qualitative",,"carbamazepine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine maleate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 14:27:00 -0400","drug-drug-interaction","evidence-supports","Benzodiazepines metabolized by hepatic oxidation (e.g., alprazolam, midazolam, triazolam, etc.) should be used with caution because the clearance of these drugs is likely to be reduced by fluvoxamine.","ncit:positive","ncit:Qualitative",,"midazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:32:33 -0500","DDI-clinical-trial","evidence-supports","Digoxin - In subjects who had received 21 days of 40 mg/day Celexa, combined administration of Celexa and digoxin (single dose of 1 mg) did not significantly affect the pharmacokinetics of either citalopram or digoxin.","ncit:negative","ncit:quantitative",,"citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","digoxin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","1","SD","Oral","1","Daily","Oral","21","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e338e89-3cf2-48eb-b6e2-a06c608c6513.html","2015-08-20 11:10:08 -0400","DDI-clinical-trial","evidence-supports","ZYTIGA is an inhibitor of the hepatic drug-metabolizing enzymes CYP2D6 and CYP2C8. In a CYP2D6 drug-drug interaction trial, the Cmax and AUC of dextromethorphan (CYP2D6 substrate) were increased 2.8- and 2.9-fold, respectively, when dextromethorphan was given with abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily. Avoid co-administration of abiraterone acetate with substrates of CYP2D6 with a narrow therapeutic index (e.g., thioridazine). If alternative treatments cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate drug [see Clinical Pharmacology (12.3)].","ncit:positive","ncit:quantitative",,"abiraterone acetate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","dextromethorphan","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","1000","UNK","UNK","Unk","Daily","UNK","Unk","Unk","2.9","Fold","Increase","Unk","UNK","UNK","2.8","Fold","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:13:55 -0400","DDI-clinical-trial","evidence-supports","Levothyroxine In healthy subjects who had received EMSAM 6 mg per 24 hours for 10 days, single dose administration with levothyroxine (150 mcg) did not alter the pharmacokinetics of either selegiline or levothyroxine [see Drug Interactions (7.4) and (7.5)].","ncit:negative","ncit:quantitative",,"EMSAM","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:object-drug-of-interaction","6","levothyroxine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","0.15","Daily","transdermal","10","SD","Oral","1","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","propafenone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/cc9e1c8c-0e2b-44e2-878b-27057f786be9.html","2015-08-20 13:57:35 -0400","drug-drug-interaction","evidence-supports","Experience with GILENYA in patients receiving concurrent therapy with drugs that slow the heart rate or atrioventricular conduction (e.g., beta blockers, digoxin, or heart rate-slowing calcium channel blockers such as diltiazem or verapamil) is limited. Because initiation of GILENYA treatment may result in an additional decrease in heart rate, concomitant use of these drugs during GILENYA initiation may be associated with severe bradycardia or heart block. Seek advice from the prescribing physician regarding the possibility to switch to drugs that do not slow the heart rate or atrioventricular conduction before initiating GILENYA. Patients who cannot switch, should have overnight continuous ECG monitoring after the first dose [see Dosage and Administration (2) and Warnings and Precautions (5.1)].","ncit:positive","ncit:Qualitative",,"GILENYA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","","verapamil","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1809bcb4-5fcc-45ca-986a-4fa5edcd4b5e.html","2015-09-29 11:41:50 -0400","drug-drug-interaction","evidence-supports","The plasma concentration of CMI has been reported to be increased by the concomitant administration of haloperidol; plasma levels of several closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of methylphenidate or hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by the concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin), and such an effect may be anticipated with CMI as well. Administration of CMI has been reported to increase the plasma levels of phenobarbital, if given concomitantly (see CLINICAL PHARMACOLOGY, Interactions).","ncit:positive","ncit:Qualitative",,"tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","CMI","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:48:13 -0500","DDI-clinical-trial","evidence-supports","Administration of 20 mg/day Lexapro for 21 days in healthy volunteers resulted in a 50% increase in Cmax and 82% increase in AUC of the beta-adrenergic blocker metoprolol (given in a single dose of 100 mg). Increased metoprolol plasma levels have been associated with decreased cardioselectivity. Coadministration of Lexapro and metoprolol had no clinically significant effects on blood pressure or heart rate. ","ncit:positive","ncit:quantitative",,"metoprolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","100","Lexapro","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","20","SD","Oral","1","Daily","Oral","21","Unk","82","Percent","Increase","Unk","UNK","UNK","50","Percent","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b8881a81-75d7-43e8-825f-37c352c146dc.html","2015-11-04 14:21:12 -0500","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics, propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:36:27 -0400","DDI-clinical-trial","evidence-supports","Cimetidine–In a study assessing disposition of sertraline (100 mg) on the second of 8 days of cimetidine administration (800 mg daily), there were significant increases in sertraline mean AUC (50%), Cmax (24%) and half-life (26%) compared to the placebo group. The clinical significance of these changes is unknown.","ncit:positive","ncit:quantitative",,"sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","100","cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","800","SD","Oral","1","Daily","Oral","8","Unk","50","Percent","Increase","Unk","UNK","UNK","24","Percent","Increase","26","Percent","Increase" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c66a11c1-3093-45ef-b348-3b196c05ba0c.html","2015-10-01 10:31:02 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dosage regimen of a TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"phenothiazines","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction","","TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f356c1b-96bd-4ef1-960c-91cf4905e6b1.html","2015-11-03 12:56:19 -0500","DDI-clinical-trial","evidence-supports","Tricyclic Antidepressants (TCAs) — In 2 studies, previously stable plasma levels of imipramine and desipramine have increased greater than 2- to 10-fold when fluoxetine has been administered in combination. This influence may persist for 3 weeks or longer after fluoxetine is discontinued. Thus, the dose of TCAs may need to be reduced and plasma TCA concentrations may need to be monitored temporarily when fluoxetine is coadministered or has been recently discontinued [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)]. ","ncit:positive","ncit:quantitative",,"desipramine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","2 to 10","Fold","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:49:45 -0500","DDI-clinical-trial","evidence-supports","Prasugrel: In healthy subjects, prasugrel increased bupropion Cmax and AUC values by 14% and 18%, respectively, and decreased Cmax and AUC values of hydroxybupropion by 32% and 24%, respectively.","ncit:positive","ncit:quantitative",,"prasugrel","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","hydroxybupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","24","Percent","Decrease","Unk","UNK","UNK","32","Percent","Decrease","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","DDI-clinical-trial","evidence-supports","There was an increase in mean repaglinide Cmax and AUC (1.7- and 2.4-fold, respectively), following repeated doses of teriflunomide and a single dose of 0.25 mg repaglinide, suggesting that teriflunomide is an inhibitor of CYP2C8 in vivo. The magnitude of interaction could be higher at the recommended repaglinide dose [see Drug Interactions (7)].","ncit:positive","ncit:quantitative",,"repaglinide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","0.25","SD","UNK","1","UNK","UNK","Unk","Unk","2.4","Fold","Increase","Unk","UNK","UNK","1.7","Fold","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5d103551-978f-472a-9c62-51e6e4dea068.html","2015-10-09 13:39:25 -0400","DDI-clinical-trial","evidence-supports","Concomitant treatment with rabeprazole (20 mg daily) and ketoconazole in healthy subjects decreased the bioavailability of ketoconazole by 30% and increased the AUC and Cmax for digoxin by 19% and 29%, respectively. Therefore, patients may need to be monitored when such drugs are taken concomitantly with rabeprazole. Co-administration of rabeprazole and antacids produced no clinically relevant changes in plasma rabeprazole concentrations.","ncit:positive","ncit:quantitative",,"ketoconazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","rabeprazole","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","UNK","UNK","Unk","Daily","Oral","Unk","Unk","19","Percent","Increase","Unk","UNK","UNK","29","Percent","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 12:50:04 -0400","drug-drug-interaction","evidence-supports","Teriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo. For a patient taking AUBAGIO, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking AUBAGIO [see Clinical Pharmacology (12.3)]","ncit:positive","ncit:Qualitative",,"Teriflunomide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","pravastatin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a16297df-3158-48db-85e5-5cd506885556.html","2015-09-29 09:27:10 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine, cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"flecainide","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a16297df-3158-48db-85e5-5cd506885556.html","2015-09-29 09:27:10 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine, cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","phenothiazines","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:48:41 -0400","DDI-clinical-trial","evidence-supports","In an in vivo, nonrandomized, interaction study, subjects (n=6) in need of treatment with an antipsychotic and antidepressant drug, showed that mirtazapine (30 mg daily) at steady state did not influence the pharmacokinetics of risperidone (up to 3 mg b.i.d.).","ncit:negative","ncit:quantitative",,"risperidone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","3","mirtazapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","30","BID","Oral","Unk","Daily","Oral","Unk","6","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f356c1b-96bd-4ef1-960c-91cf4905e6b1.html","2015-09-10 14:36:47 -0400","drug-drug-interaction","evidence-supports","Benzodiazepines — The half-life of concurrently administered diazepam may be prolonged in some patients [see Clinical Pharmacology (12.3)]. Coadministration of alprazolam and fluoxetine has resulted in increased alprazolam plasma concentrations and in further psychomotor performance decrement due to increased alprazolam levels. ","ncit:positive","ncit:Qualitative",,"fluoxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","","alprazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c66a11c1-3093-45ef-b348-3b196c05ba0c.html","2015-10-29 11:36:33 -0400","drug-drug-interaction","evidence-supports","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dosage regimen of a TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","ncit:positive","ncit:Qualitative",,"TCA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction",,"cimetidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1809bcb4-5fcc-45ca-986a-4fa5edcd4b5e.html","2015-09-29 09:58:27 -0400","drug-drug-interaction","evidence-supports","The plasma concentration of CMI has been reported to be increased by the concomitant administration of haloperidol; plasma levels of several closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of methylphenidate or hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by the concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin), and such an effect may be anticipated with CMI as well. Administration of CMI has been reported to increase the plasma levels of phenobarbital, if given concomitantly (see CLINICAL PHARMACOLOGY, Interactions).","ncit:positive","ncit:Qualitative",,"tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","","hepatic enzyme inhibitors","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-09-14 11:31:14 -0400","DDI-clinical-trial","evidence-supports","Daily oral dosing of paroxetine (30 mg once daily) increased steady-state AUC0-24, Cmax, and Cmin values of procyclidine (5 mg oral once daily) by 35%, 37%, and 67%, respectively, compared to procyclidine alone at steady state. If anticholinergic effects are seen, the dose of procyclidine should be reduced.","ncit:positive","ncit:quantitative",,"paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","30","procyclidine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","5","Daily","Oral","Unk","Daily","Oral","Unk","Unk","35","Percent","Increase","Unk","UNK","UNK","37","Percent","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:37:51 -0400","drug-drug-interaction","evidence-supports","Drugs Metabolized by P450 2D6–Many drugs effective in the treatment of major depressive disorder, e.g., the SSRIs, including sertraline, and most tricyclic antidepressant drugs effective in the treatment of major depressive disorder inhibit the biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase), and, thus, may increase the plasma concentrations of co-administered drugs that are metabolized by P450 2D6. The drugs for which this potential interaction is of greatest concern are those metabolized primarily by 2D6 and which have a narrow therapeutic index, e.g., the tricyclic antidepressant drugs effective in the treatment of major depressive disorder and the Type 1C antiarrhythmics propafenone and flecainide. The extent to which this interaction is an important clinical problem depends on the extent of the inhibition of P450 2D6 by the antidepressant and the therapeutic index of the co-administered drug. There is variability among the drugs effective in the treatment of major depressive disorder in the extent of clinically important 2D6 inhibition, and in fact sertraline at lower doses has a less prominent inhibitory effect on 2D6 than some others in the class. Nevertheless, even sertraline has the potential for clinically important 2D6 inhibition. Consequently, concomitant use of a drug metabolized by P450 2D6 with sertraline may require lower doses than usually prescribed for the other drug. Furthermore, whenever sertraline is withdrawn from co-therapy, an increased dose of the co-administered drug may be required (see Tricyclic Antidepressant Drugs Effective in the Treatment of Major Depressive Disorder under PRECAUTIONS).","ncit:positive","ncit:Qualitative",,"propafenone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","","sertraline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:07:34 -0500","DDI-clinical-trial","evidence-supports","In a second healthy volunteer study, ritonavir 600 mg twice daily decreased the AUC and Cmax of bupropion by 66% and 62% respectively. The exposure of the hydroxybupropion metabolite was decreased by 78%, the threohydrobupropion decreased by 50%, and the erythrohydrobupropion decreased by 68%. ","ncit:positive","ncit:quantitative","Exposure decreased by 78%","ritonavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","hydroxybupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","BID","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-10-28 14:38:28 -0400","DDI-clinical-trial","evidence-supports","An in vivo study suggests that drugs which inhibit CYP2D6, such as paroxetine, will elevate plasma levels of thioridazine. Therefore, it is recommended that paroxetine not be used in combination with thioridazine (see CONTRAINDICATIONS and PRECAUTIONS). ","ncit:positive","ncit:quantitative",,"thioridazine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","paroxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:05:45 -0500","DDI-clinical-trial","evidence-supports","In a healthy volunteer study, ritonavir 100 mg twice daily reduced the AUC and Cmax of bupropion by 22% and 21%, respectively. The exposure of the hydroxybupropion metabolite was decreased by 23%, the threohydrobupropion decreased by 38%, and the erythrohydrobupropion decreased by 48%. ","ncit:positive","ncit:quantitative","Exposure decreased by 38%","ritonavir","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","threohydrobupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","BID","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/f371258d-91b3-4b6a-ac99-434a1964c3af.html","2015-10-29 09:45:11 -0400","drug-drug-interaction","evidence-supports","Concomitant use of FETZIMA with alprazolam or carbamazepine, substrates of CYP3A4, had no significant effect on alprazolam or carbamazepine plasma concentrations ","ncit:negative","ncit:Qualitative",,"FETZIMA","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction",,"alprazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 14:27:00 -0400","drug-drug-interaction","evidence-supports","The clearance of benzodiazepines metabolized by glucuronidation (e.g., lorazepam, oxazepam, temazepam) is unlikely to be affected by fluvoxamine. ","ncit:negative","ncit:Qualitative",,"fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"lorazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e338e89-3cf2-48eb-b6e2-a06c608c6513.html","2015-08-20 11:32:27 -0400","DDI-clinical-trial","evidence-supports","In a CYP2C8 drug-drug interaction trial in healthy subjects, the AUC of pioglitazone was increased by 46% when pioglitazone was given together with a single dose of 1,000 mg abiraterone acetate [see Drug Interactions (7.2)].","ncit:positive","ncit:quantitative",,"pioglitazone","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","1000","abiraterone acetate","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","SD","UNK","1","Unk","46","Percent","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:32:17 -0500","DDI-clinical-trial","evidence-supports","Combined administration of racemic citalopram (40 mg/day for 14 days) and carbamazepine (titrated to 400 mg/day for 35 days) did not significantly affect the pharmacokinetics of carbamazepine, a CYP3A4 substrate. Although trough citalopram plasma levels were unaffected, given the enzyme-inducing properties of carbamazepine, the possibility that carbamazepine might increase the clearance of escitalopram should be considered if the two drugs are coadministered. ","ncit:negative","ncit:quantitative",,"citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","carbamazepine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","400","Daily","Oral","35","Daily","Oral","14","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/0177d783-773c-41bf-9db9-eb7e5c64474a.html","2015-11-05 10:40:12 -0500","drug-drug-interaction","evidence-supports","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7-10% of caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of the isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.","ncit:positive","ncit:Qualitative",,"phenothiazines","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:precipitant-drug-of-interaction",,"tricyclic antidepressants","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","DDI-clinical-trial","evidence-supports","A study of multiple doses of fluvoxamine maleate (50 mg b.i.d.) in healthy male volunteers (N = 12) and a single dose of lorazepam (4 mg single dose) indicated no significant pharmacokinetic interaction. On average, both lorazepam alone and lorazepam with fluvoxamine produced substantial decrements in cognitive functioning; however, the coadministration of fluvoxamine and lorazepam did not produce larger mean decrements compared to lorazepam alone. ","ncit:negative","ncit:quantitative",,"lorazepam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","4","fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","50","SD","Oral","1","BID","Oral","Unk","12","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/829a4f51-c882-4b64-81f3-abfb03a52ebe.html","2015-10-29 08:58:27 -0400","DDI-clinical-trial","evidence-supports","When duloxetine 60 mg was co-administered with fluvoxamine 100 mg, a potent CYP1A2 inhibitor, to male subjects (n=14) duloxetine AUC was increased approximately 6-fold, the Cmax was increased about 2.5-fold, and duloxetine t1/2 was increased approximately 3-fold. Other drugs that inhibit CYP1A2 metabolism include cimetidine and quinolone antimicrobials such as ciprofloxacin and enoxacin [see WARNINGS AND PRECAUTIONS (5.12)]. ","ncit:positive","ncit:quantitative",,"fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","duloxetine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","60","UNK","Oral","Unk","UNK","Oral","Unk","14","6","Fold","Increase","Unk","UNK","UNK","2.5","Fold","Increase","3","Fold","Increase" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:15:31 -0500","DDI-clinical-trial","evidence-supports","Efavirenz: In a study of healthy volunteers, efavirenz 600 mg once daily for 2 weeks reduced the AUC and Cmax of bupropion by approximately 55% and 34%, respectively. The AUC of hydroxybupropion was unchanged, whereas Cmax of hydroxybupropion was increased by 50%.","ncit:positive","ncit:quantitative",,"hydroxybupropion","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/metabolite","dikbD2R:object-drug-of-interaction","Unk","efavirenz","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","UNK","UNK","Unk","Daily","Oral","14","Unk","Unk","UNK","UNK","Unk","UNK","UNK","50","Percent","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","A clinically significant fluvoxamine interaction is possible with drugs having a narrow therapeutic ratio such as pimozide, warfarin, theophylline, certain benzodiazepines, omeprazole and phenytoin. If fluvoxamine maleate tablets are to be administered together with a drug that is eliminated via oxidative metabolism and has a narrow therapeutic window, plasma levels and/or pharmacodynamic effects of the latter drug should be monitored closely, at least until steady-state conditions are reached [see Contraindications (4) and Warnings and Precautions (5)]. ","ncit:positive","ncit:Qualitative",,"fluvoxamine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"warfarin","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 14:00:44 -0500","DDI-clinical-trial","evidence-supports","Metoprolol - Administration of 40 mg/day Celexa for 22 days resulted in a two-fold increase in the plasma levels of the beta-adrenergic blocker metoprolol. Increased metoprolol plasma levels have been associated with decreased cardioselectivity. Coadministration of Celexa and metoprolol had no clinically significant effects on blood pressure or heart rate.","ncit:positive","ncit:quantitative",,"metoprolol","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","Celexa","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/drug-product","dikbD2R:precipitant-drug-of-interaction","40","UNK","UNK","Unk","Daily","Oral","22","Unk","Unk","UNK","UNK","Unk","UNK","UNK","2","Fold","Increase","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/f371258d-91b3-4b6a-ac99-434a1964c3af.html","2015-10-29 09:45:10 -0400","DDI-clinical-trial","evidence-supports","No dose adjustment of FETZIMA is needed when co-administered with a CYP3A4 inducer or substrate. In vivo studies showed no clinically meaningful change in levomilnacipran exposure when co-administered with the CYP3A4 inducer carbamazepine or the CYP3A4 substrate alprazolam (see Figure 1). ","ncit:negative","ncit:quantitative",,"levomilnacipran","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","Unk","carbamazepine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:48:14 -0400","DDI-clinical-trial","evidence-supports","In healthy, CYP2D6 extensive metabolizer patients (n=32), amitriptyline (75 mg daily), at steady state, did not cause relevant changes in the pharmacokinetics of steady state mirtazapine (30 mg daily); mirtazapine also did not cause relevant changes to the pharmacokinetics of amitriptyline.","ncit:negative","ncit:quantitative",,"amitriptyline","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","75","mirtazapine","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","30","Daily","Oral","Unk","Daily","Oral","Unk","32","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" -"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:33:30 -0500","DDI-clinical-trial","evidence-supports","Combined administration of racemic citalopram (titrated to 40 mg/day for 28 days) and the CYP3A4 substrate triazolam (single dose of 0.25 mg) did not significantly affect the pharmacokinetics of either citalopram or triazolam. ","ncit:negative","ncit:quantitative",,"citalopram","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","triazolam","http://dbmi-icode-01.dbmi.pitt.edu:2020/vocab/resource/active-ingredient","dikbD2R:object-drug-of-interaction","0.25","SD","Oral","1","Daily","Oral","28","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" diff --git a/translation/RDB_ETL/pkddi-katrina-latest-08152016.csv b/translation/RDB_ETL/pkddi-katrina-latest-08152016.csv new file mode 100644 index 0000000..4cc344d --- /dev/null +++ b/translation/RDB_ETL/pkddi-katrina-latest-08152016.csv @@ -0,0 +1,449 @@ +"source","date","assertionType","evidenceType","prefix","exactText","suffix","modality","statementType","comment","drug1Lab","drug1Type","drug1Role","dose1","drug2Lab","drug2Type","drug2Role","dose2","objectRegimens","objectFormulation","objectDuration","preciptRegimens","preciptFormulation","preciptDuration","numOfParticipants","auc","aucType","aucDirection","cl","clType","clDirection","cmax","cmaxType","cmaxDirection","t12","t12Type","t12Direction" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:48:50 -0400","drug-drug-interaction","evidence-supports","nsporter 3 (OAT3) substrates ","Teriflunomide inhibits the activity of OAT3 in vivo. In patients taking AUBAGIO, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) which are OAT3 substrates as required [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"furosemide","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ea35caf8-c8c8-481a-97a2-25f68cbc240b.html","2015-10-29 11:09:04 -0400","drug-drug-interaction","evidence-supports","e in plasma AUC of the TCA ). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction",,"quinidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:42:22 -0400","drug-drug-interaction","evidence-supports","nical Pharmacology (12.3) ] . ","No dose adjustment of alprazolam, ibuprofen, levothyroxine, olanzapine, risperdione, warfarin, or strong CYP3A4 inhibitors (e.g., ketoconazole) is necessary when these drugs are used in combination with EMSAM. EMSAM had no clinically relevant effect on pharmacokinetics of these drugs.","","ncit:negative","ncit:Qualitative",,"olanzapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","EMSAM","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:17:34 -0400","DDI-clinical-trial","evidence-supports","","Risperidone In subjects who had received EMSAM 6 mg per 24 hours for 10 days, co-administration with risperidone (2 mg per day for 7 days), a substrate for CYP2D6, did not affect the pharmacokinetics of selegiline or risperidone [see Drug Interactions (7.4) and (7.5)]. Warfarin","","ncit:negative","ncit:quantitative",,"EMSAM","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","6","risperidone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","2","Daily","Oral","7","Daily","transdermal","10","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e338e89-3cf2-48eb-b6e2-a06c608c6513.html","2015-08-20 11:17:13 -0400","DDI-clinical-trial","evidence-supports","CYP2C9, CYP2C19 and CYP3A4/5. ","In an in vivo drug-drug interaction trial, the Cmax and AUC of dextromethorphan (CYP2D6 substrate) were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily (plus prednisone 5 mg twice daily). The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold [see Drug Interactions (7.2)].","","ncit:positive","ncit:quantitative",,"dextromethorphan","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","1000","abiraterone acetate","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","30","UNK","UNK","Unk","Daily","UNK","Unk","Unk","2.9","Fold","Increase","Unk","UNK","UNK","2.8","Fold","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f356c1b-96bd-4ef1-960c-91cf4905e6b1.html","2015-11-02 16:13:06 -0500","DDI-clinical-trial","evidence-supports","","Olanzapine — Fluoxetine (60 mg single dose or 60 mg daily dose for 8 days) causes a small (mean 16%) increase in the maximum concentration of olanzapine and a small (mean 16%) decrease in olanzapine clearance. The magnitude of the impact of this factor is small in comparison to the overall variability between individuals, and therefore dose modification is not routinely recommended. ","","ncit:positive","ncit:quantitative",,"olanzapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","Fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","60","UNK","UNK","Unk","Daily","Oral","8","Unk","Unk","UNK","UNK","16","Percent","Decrease","16","Percent","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-09-14 11:21:10 -0400","drug-drug-interaction","evidence-supports","","An in vivo interaction study involving the coadministration under steady-state conditions of paroxetine and terfenadine, a substrate for cytochrome CYP3A4, revealed no effect of paroxetine on terfenadine pharmacokinetics."," In addition,","ncit:negative","ncit:Qualitative",,"paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","terfenadine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/cc9e1c8c-0e2b-44e2-878b-27057f786be9.html","2015-08-20 13:57:35 -0400","drug-drug-interaction","evidence-supports","beta blockers or diltiazem ) ","Experience with GILENYA in patients receiving concurrent therapy with drugs that slow the heart rate or atrioventricular conduction (e.g., beta blockers, digoxin, or heart rate-slowing calcium channel blockers such as diltiazem or verapamil) is limited. Because initiation of GILENYA treatment may result in an additional decrease in heart rate, concomitant use of these drugs during GILENYA initiation may be associated with severe bradycardia or heart block. Seek advice from the prescribing physician regarding the possibility to switch to drugs that do not slow the heart rate or atrioventricular conduction before initiating GILENYA. Patients who cannot switch, should have overnight continuous ECG monitoring after the first dose [see Dosage and Administration (2) and Warnings and Precautions (5.1)]","","ncit:positive","ncit:Qualitative",,"beta blockers","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","GILENYA","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:46:43 -0400","DDI-clinical-trial","evidence-supports","ocking ability of atenolol . ","Digoxin–In a placebo-controlled trial in normal volunteers, administration of sertraline for 17 days (including 200 mg/day for the last 10 days) did not change serum digoxin levels or digoxin renal clearance.","","ncit:negative","ncit:quantitative",,"digoxin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","sertraline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","UNK","UNK","Unk","Daily","Oral","17","10","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:32:33 -0500","DDI-clinical-trial","evidence-supports","","Digoxin - In subjects who had received 21 days of 40 mg/day Celexa, combined administration of Celexa and digoxin (single dose of 1 mg) did not significantly affect the pharmacokinetics of either citalopram or digoxin.","","ncit:negative","ncit:quantitative",,"citalopram","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","40","digoxin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","1","Daily","Oral","21","SD","Oral","1","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1809bcb4-5fcc-45ca-986a-4fa5edcd4b5e.html","2015-09-29 09:58:27 -0400","drug-drug-interaction","evidence-supports","er tricyclic antidepressants. ","The plasma concentration of CMI has been reported to be increased by the concomitant administration of haloperidol; plasma levels of several closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of methylphenidate or hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by the concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin), and such an effect may be anticipated with CMI as well. Administration of CMI has been reported to increase the plasma levels of phenobarbital, if given concomitantly (see CLINICAL PHARMACOLOGY, Interactions).","","ncit:positive","ncit:Qualitative",,"tricyclic antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","hepatic enzyme inducers","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:36:27 -0400","DDI-clinical-trial","evidence-supports"," of these changes is unknown. ","In a placebo-controlled trial in normal volunteers, the administration of two doses of sertraline did not significantly alter steady-state lithium levels or the renal clearance of lithium.","","ncit:negative","ncit:quantitative",,"sertraline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","lithium","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","pharmacokinetics of lithium . ","Lorazepam-There was no pharmacokinetic interaction between a single dose of Savella (50 mg) and lorazepam (1.5 mg). ","","ncit:negative","ncit:quantitative",,"lorazepam","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","50","Savella","dikbD2R:drug-product","dikbD2R:object-drug-of-interaction","1.5","SD","tablet","1","SD","tablet","1","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-10-28 14:38:28 -0400","DDI-clinical-trial","evidence-supports","). Drug-Drug Interactions  ","In vitro drug interaction studies reveal that paroxetine inhibits CYP2D6. Clinical drug interaction studies have been performed with substrates of CYP2D6 and show that paroxetine can inhibit the metabolism of drugs metabolized by CYP2D6 including desipramine, risperidone, and atomoxetine (see PRECAUTIONS: Drug Interactions)","","ncit:positive","ncit:quantitative",,"paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","atomoxetine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports","","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary",")","ncit:positive","ncit:Qualitative",,"flecainide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-10-28 15:23:31 -0400","DDI-clinical-trial","evidence-supports","IONS and WARNINGS . Pimozide ","In a controlled study of healthy volunteers, after paroxetine was titrated to 60 mg daily, coadministration of a single dose of 2 mg pimozide was associated with mean increases in pimozide AUC of 151% and Cmax of 62%, compared to pimozide administered alone. The increase in pimozide AUC and Cmax is due to the CYP2D6 inhibitory properties of paroxetine. Due to the narrow therapeutic index of pimozide and its known ability to prolong the QT interval, concomitant use of pimozide and paroxetine is contraindicated (see CONTRAINDICATIONS).","","ncit:positive","ncit:quantitative",,"pimozide","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","2","paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","60","SD","Oral","1","Daily","Oral","Unk","Unk","151","Percent","Increase","Unk","UNK","UNK","62","Percent","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:56:21 -0500","DDI-clinical-trial","evidence-supports","","Carbamazepine - Combined administration of Celexa (40 mg/day for 14 days) and carbamazepine (titrated to 400 mg/day for 35 days) did not significantly affect the pharmacokinetics of carbamazepine, a CYP3A4 substrate. Although trough citalopram plasma levels were unaffected, given the enzyme-inducing properties of carbamazepine, the possibility that carbamazepine might increase the clearance of citalopram should be considered if the two drugs are coadministered.","","ncit:negative","ncit:quantitative",,"Celexa","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","40","carbamazepine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","400","Daily","Oral","35","Daily","Oral","14","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/55816042-946d-4bec-9461-bd998628ff45.html","2015-10-14 11:57:06 -0400","drug-drug-interaction","evidence-supports","tantly administered rifampin. ","Rifampin has been reported to substantially decrease the plasma concentrations of the following antiviral drugs: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir. These antiviral drugs must not be co-administered with rifampin. (See CONTRAINDICATIONS.) ","","ncit:positive","ncit:Qualitative",,"Rifampin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","tipranavir","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:13:01 -0400","DDI-clinical-trial","evidence-supports","","Ketoconazole Seven-day treatment with ketoconazole (200 mg per day), a potent inhibitor of CYP3A4, did not affect the steady-state pharmacokinetics of selegiline in subjects who received EMSAM 6 mg per 24 hours for 7 days and no differences in the pharmacokinetics of ketoconazole were observed [see Drug Interactions (7.4) and (7.5)]. ","","ncit:negative","ncit:quantitative",,"selegiline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","6","ketoconazole","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","200","Daily","Oral","7","Daily","transdermal","7","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-09-14 11:32:07 -0400","drug-drug-interaction","evidence-supports","d. Fosamprenavir / Ritonavir ","Coadministration of fosamprenavir/ritonavir with paroxetine significantly decreased plasma levels of paroxetine. Any dose adjustment should be guided by clinical effect (tolerability and efficacy)","","ncit:positive","ncit:Qualitative",,"paroxetine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fosamprenavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:22:34 -0500","DDI-clinical-trial","evidence-supports"," 7.8 Digoxin ","In subjects who had received 21 days of 40 mg/day racemic citalopram, combined administration of citalopram and digoxin (single dose of 1 mg) did not significantly affect the pharmacokinetics of either citalopram or digoxin. ","","ncit:negative","ncit:quantitative",,"digoxin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","1","citalopram","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","SD","Oral","1","Daily","Oral","21","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f356c1b-96bd-4ef1-960c-91cf4905e6b1.html","2015-09-10 14:36:47 -0400","drug-drug-interaction","evidence-supports","","Antipsychotics — Some clinical data suggests a possible pharmacodynamic and/or pharmacokinetic interaction between SSRIs and antipsychotics. Elevation of blood levels of haloperidol and clozapine has been observed in patients receiving concomitant fluoxetine. ","","ncit:positive","ncit:Qualitative",,"fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","haloperidol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a16297df-3158-48db-85e5-5cd506885556.html","2015-09-29 09:27:10 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine, cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"quinidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-09-10 15:01:13 -0400","drug-drug-interaction","evidence-supports","yclic Antidepressants (TCAs) ","Significantly increased plasma TCA levels have been reported with the coadministration of fluvoxamine maleate and amitriptyline, clomipramine or imipramine. Caution is indicated with the coadministration of fluvoxamine maleate tablets and TCAs; plasma TCA concentrations may need to be monitored, and the dose of TCA may need to be reduced.","","ncit:positive","ncit:Qualitative",,"fluvoxamine maleate","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","imipramine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ea35caf8-c8c8-481a-97a2-25f68cbc240b.html","2015-09-29 09:04:36 -0400","drug-drug-interaction","evidence-supports","e in plasma AUC of the TCA ). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"sertraline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/829a4f51-c882-4b64-81f3-abfb03a52ebe.html","2015-10-29 09:10:04 -0400","DDI-clinical-trial","evidence-supports"," Drugs Metabolized by CYP2D6 ","Duloxetine is a moderate inhibitor of CYP2D6. When duloxetine was administered (at a dose of 60 mg twice daily) in conjunction with a single 50 mg dose of desipramine, a CYP2D6 substrate, the AUC of desipramine increased 3-fold [see WARNINGS AND PRECAUTIONS (5.12)]. ","","ncit:positive","ncit:quantitative",,"desipramine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","50","duloxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","60","SD","Oral","1","BID","Oral","Unk","Unk","3","Fold","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:33:12 -0400","DDI-clinical-trial","evidence-supports"," Phenytoin ","In healthy male patients (n=18), phenytoin (200 mg daily) increased mirtazapine (30 mg daily) clearance about 2-fold, resulting in a decrease in average plasma mirtazapine concentrations of 45%. Mirtazapine did not significantly affect the pharmacokinetics of phenytoin.","","ncit:positive","ncit:quantitative",,"phenytoin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","mirtazapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","30","Daily",,"Unk","Daily","Oral","Unk","18","Unk","UNK","UNK","2","Fold","Increase","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","0 mg) and lorazepam (1.5 mg). ","Pregabalin-There were no clinically significant changes in the steady-state pharmacokinetics of milnacipran or pregabalin following twice a day co-administration of 50 mg milnacipran and 150 mg pregabalin. ","","ncit:negative","ncit:quantitative",,"pregabalin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","50","milnacipran","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","150","BID","tablet","Unk","BID","tablet","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 13:28:11 -0400","DDI-clinical-trial","evidence-supports","","Ibuprofen In subjects who had received EMSAM 6 mg per 24 hours for 11 days, combined administration with the CYP2C9 substrate ibuprofen (800 mg single dose) did not affect the pharmacokinetics of either selegiline or ibuprofen [see Drug Interactions (7.4) and (7.5)]. ","","ncit:negative","ncit:quantitative",,"ibuprofen","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","800","EMSAM","dikbD2R:drug-product","dikbD2R:object-drug-of-interaction","6","Daily","transdermal","11","SD","Oral","1","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a16297df-3158-48db-85e5-5cd506885556.html","2015-09-29 09:27:10 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine, cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","selective serotonin reuptake inhibitors","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/cc9e1c8c-0e2b-44e2-878b-27057f786be9.html","2015-08-20 13:57:35 -0400","drug-drug-interaction","evidence-supports","beta blockers or diltiazem ) ","Experience with GILENYA in patients receiving concurrent therapy with drugs that slow the heart rate or atrioventricular conduction (e.g., beta blockers, digoxin, or heart rate-slowing calcium channel blockers such as diltiazem or verapamil) is limited. Because initiation of GILENYA treatment may result in an additional decrease in heart rate, concomitant use of these drugs during GILENYA initiation may be associated with severe bradycardia or heart block. Seek advice from the prescribing physician regarding the possibility to switch to drugs that do not slow the heart rate or atrioventricular conduction before initiating GILENYA. Patients who cannot switch, should have overnight continuous ECG monitoring after the first dose [see Dosage and Administration (2) and Warnings and Precautions (5.1)].","","ncit:positive","ncit:Qualitative",,"digoxin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","GILENYA","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1809bcb4-5fcc-45ca-986a-4fa5edcd4b5e.html","2015-09-29 11:41:50 -0400","drug-drug-interaction","evidence-supports","as well."," Administration of CMI has been reported to increase the plasma levels of phenobarbital, if given concomitantly","","ncit:positive","ncit:Qualitative",,"phenobarbital","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","CMI","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:48:50 -0400","drug-drug-interaction","evidence-supports","nsporter 3 (OAT3) substrates ","Teriflunomide inhibits the activity of OAT3 in vivo. In patients taking AUBAGIO, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) which are OAT3 substrates as required [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","methotrexate","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:43:15 -0400","drug-drug-interaction","evidence-supports","ffect of Other Drugs on EMSAM ","Carbamazepine is contraindicated with MAOIs, including selegiline [see Contraindications (4), Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)]. ","","ncit:positive","ncit:Qualitative",,"selegiline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Carbamazepine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports"," be an inhibitor of P450 2D6. ","The plasma concentration of imipramine may increase when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decrease by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), and adjustment of the dosage of imipramine may therefore be necessary.","","ncit:positive","ncit:Qualitative",,"imipramine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:43:15 -0400","drug-drug-interaction","evidence-supports","nical Pharmacology (12.3) ] . ","No dose adjustment for EMSAM is needed when EMSAM is used concomitantly with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and CYP3A4 inhibitors (e.g., ketoconazole). No clinically meaningful change in selegiline exposure was seen when EMSAM was co-administered with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and ketoconazole [see Clinical Pharmacology (12.3)]. ","","ncit:negative","ncit:Qualitative",,"ketoconazole","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","EMSAM","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:48:13 -0400","DDI-clinical-trial","evidence-supports"," Amitriptyline ","In healthy, CYP2D6 extensive metabolizer patients (n=32), amitriptyline (75 mg daily), at steady state, did not cause relevant changes in the pharmacokinetics of steady state mirtazapine (30 mg daily); mirtazapine also did not cause relevant changes to the pharmacokinetics of amitriptyline.","","ncit:negative","ncit:quantitative",,"amitriptyline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","75","mirtazapine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","30","Daily","Oral","Unk","Daily","Oral","Unk","32","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:39:59 -0400","DDI-clinical-trial","evidence-supports","olol and Other Beta-Blockers ","Coadministration of fluvoxamine maleate 100 mg per day and propranolol 160 mg per day in normal volunteers resulted in a mean 5-fold increase (range 2 to 17) in minimum propranolol plasma concentrations. In this study, there was a slight potentiation of the propranolol-induced reduction in heart rate and reduction in the exercise diastolic pressure. ","","ncit:positive","ncit:quantitative",,"propranolol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","160","fluvoxamine maleate","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","Daily","Oral","Unk","Daily","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","5","Fold","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ea35caf8-c8c8-481a-97a2-25f68cbc240b.html","2015-09-29 09:04:36 -0400","drug-drug-interaction","evidence-supports","e in plasma AUC of the TCA ). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","selective serotonin reuptake inhibitors","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:48:50 -0400","drug-drug-interaction","evidence-supports","nsporter 3 (OAT3) substrates ","Teriflunomide inhibits the activity of OAT3 in vivo. In patients taking AUBAGIO, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) which are OAT3 substrates as required [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"penicillin G","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e338e89-3cf2-48eb-b6e2-a06c608c6513.html","2015-08-20 11:10:08 -0400","DDI-clinical-trial","evidence-supports","ibit or Induce CYP3A4 Enzymes ","Based on in vitro data, ZYTIGA is a substrate of CYP3A4. In a dedicated drug interaction trial, co-administration of rifampin, a strong CYP3A4 inducer, decreased exposure of abiraterone by 55%. Avoid concomitant strong CYP3A4 inducers during ZYTIGA treatment. If a strong CYP3A4 inducer must be co-administered, increase the ZYTIGA dosing frequency [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].","","ncit:positive","ncit:quantitative",,"abiraterone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","rifampin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","55","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:17:34 -0400","DDI-clinical-trial","evidence-supports","","Warfarin Warfarin is a substrate for CYP2C9 and CYP3A4 metabolism pathways. In healthy volunteers titrated with Coumadin®# (warfarin sodium) to clinical levels of anticoagulation (INR of 1.5 to 2), co-administration with EMSAM 6 mg per 24 hours for 7 days did not affect the pharmacokinetics of the individual warfarin enantiomers. EMSAM did not alter the clinical pharmacodynamic effects of warfarin as measured by INR, Factor VII or Factor X levels [see Drug Interactions (7.4) and (7.5)].","","ncit:negative","ncit:quantitative",,"EMSAM","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","6","warfarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","Daily","transdermal","7","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-09-29 11:28:40 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type IC antiarrhythmics propafenone and flecainide). While all the SSRIs, e.g., fluoxetine, sertraline, paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","quinidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f356c1b-96bd-4ef1-960c-91cf4905e6b1.html","2015-11-03 12:56:19 -0500","DDI-clinical-trial","evidence-supports","","Tricyclic Antidepressants (TCAs) — In 2 studies, previously stable plasma levels of imipramine and desipramine have increased greater than 2- to 10-fold when fluoxetine has been administered in combination. This influence may persist for 3 weeks or longer after fluoxetine is discontinued. Thus, the dose of TCAs may need to be reduced and plasma TCA concentrations may need to be monitored temporarily when fluoxetine is coadministered or has been recently discontinued [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)]. ","","ncit:positive","ncit:quantitative",,"imipramine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","2 to 10","Fold","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"sertraline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e338e89-3cf2-48eb-b6e2-a06c608c6513.html","2015-08-20 11:30:25 -0400","DDI-clinical-trial","evidence-supports","e Drug Interactions (7.2) ] . ","In a clinical study to determine the effects of abiraterone acetate 1,000 mg daily (plus prednisone 5 mg twice daily) on a single 100 mg dose of the CYP1A2 substrate theophylline, no increase in systemic exposure of theophylline was observed.","","ncit:negative","ncit:quantitative",,"abiraterone acetate","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","theophylline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","1000","SD","UNK","1","Daily","UNK","Unk","Unk","0","Percent","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","pran and 150 mg pregabalin . ","Warfarin-Steady-state milnacipran (200 mg/day) did not affect the pharmacokinetics of R-warfarin and S-warfarin or the pharmacodynamics (as assessed by measurement of prothrombin INR) of a single dose of 25 mg warfarin. The pharmacokinetics of Savella were not altered by warfarin. ","","ncit:negative","ncit:quantitative",,"milnacipran","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","25","warfarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","200","SD","tablet","1","Daily","tablet","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/7c295b64-ec39-42ec-9f02-da5b42e775e1.html","2015-08-20 10:29:59 -0400","DDI-clinical-trial","evidence-supports","de induces hepatic enzymes . ","In vitro studies have shown that R-bicalutamide is an inhibitor of CYP 3A4 with lesser inhibitory effects on CYP 2C9, 2C19 and 2D6 activity. Clinical studies have shown that with co-administration of bicalutamide, mean midazolam (a CYP 3A4 substrate) levels may be increased 1.5 fold (for Cmax) and 1.9 fold (for AUC). Hence, caution should be exercised when bicalutamide is co-administered with CYP 3A4 substrates.","","ncit:positive","ncit:quantitative",,"bicalutamide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","midazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","1.9","Fold","Increase","Unk","UNK","UNK","1.5","Fold","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:36:27 -0400","DDI-clinical-trial","evidence-supports","dDOSAGE AND ADMINISTRATION . ","Drugs Metabolized by P450 3A4–In three separate in vivo interaction studies, sertraline was co-administered with cytochrome P450 3A4 substrates, terfenadine, carbamazepine, or cisapride under steady-state conditions. The results of these studies indicated that sertraline did not increase plasma concentrations of terfenadine, carbamazepine, or cisapride. These data indicate that sertraline’s extent of inhibition of P450 3A4 activity is not likely to be of clinical significance. Results of the interaction study with cisapride indicate that sertraline 200 mg (q.d.) induces the metabolism of cisapride (cisapride AUC and Cmax were reduced by about 35%).","","ncit:negative","ncit:quantitative",,"carbamazepine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","sertraline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:48:50 -0400","drug-drug-interaction","evidence-supports","nsporter 3 (OAT3) substrates ","Teriflunomide inhibits the activity of OAT3 in vivo. In patients taking AUBAGIO, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) which are OAT3 substrates as required [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","cimetidine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:32:33 -0500","DDI-clinical-trial","evidence-supports","","Cimetidine - In subjects who had received 21 days of 40 mg/day Celexa, combined administration of 400 mg twice a day cimetidine for 8 days resulted in an increase in citalopram AUC and Cmax of 43% and 39%, respectively. ","","ncit:positive","ncit:quantitative",,"cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","400","citalopram","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","40","Daily","Oral","21","BID","Oral","8","Unk","43","Percent","Increase","Unk","UNK","UNK","39","Percent","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:35:22 -0500","DDI-clinical-trial","evidence-supports"," 7.17 Ritonavir ","Combined administration of a single dose of ritonavir (600 mg), both a CYP3A4 substrate and a potent inhibitor of CYP3A4, and escitalopram (20 mg) did not affect the pharmacokinetics of either ritonavir or escitalopram. ","","ncit:negative","ncit:quantitative",,"ritonavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","escitalopram","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","20","UNK","Oral","Unk","UNK","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 12:50:04 -0400","drug-drug-interaction","evidence-supports"," B3 (OATP1B1/1B3) substrates ","Teriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo. For a patient taking AUBAGIO, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking AUBAGIO [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","rifampin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:27:26 -0500","DDI-clinical-trial","evidence-supports","","Coadministration of racemic citalopram (40 mg/day for 10 days) and lithium (30 mmol/day for 5 days) had no significant effect on the pharmacokinetics of citalopram or lithium. Nevertheless, plasma lithium levels should be monitored with appropriate adjustment to the lithium dose in accordance with standard clinical practice. Because lithium may enhance the serotonergic effects of escitalopram, caution should be exercised when Lexapro and lithium are coadministered","","ncit:negative","ncit:quantitative",,"citalopram","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","40","lithium","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","30 mmol","Daily","Oral","10","Daily","IV","5","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 12:50:04 -0400","drug-drug-interaction","evidence-supports"," B3 (OATP1B1/1B3) substrates ","Teriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo. For a patient taking AUBAGIO, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking AUBAGIO [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","simvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","drug-drug-interaction","evidence-supports","see Drug Interactions (7) ] . ","Teriflunomide did not affect the pharmacokinetics of bupropion (a CYP2B6 substrate), midazolam (a CYP3A4 substrate), S-warfarin (a CYP2C9 substrate), omeprazole (a CYP2C19 substrate), and metoprolol (a CYP2D6 substrate).","","ncit:negative","ncit:Qualitative",,"metoprolol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-09-14 11:31:14 -0400","DDI-clinical-trial","evidence-supports","ld be reduced. Beta-Blockers ","In a study where propranolol (80 mg twice daily) was dosed orally for 18 days, the established steady-state plasma concentrations of propranolol were unaltered during coadministration with paroxetine (30 mg once daily) for the final 10 days. The effects of propranolol on paroxetine have not been evaluated (see ADVERSE REACTIONS: Postmarketing Reports).","","ncit:negative","ncit:quantitative",,"propranolol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","80","paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","30","BID","Oral","18","Daily","Oral","10","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a9ff32c4-3bcf-4e51-ae8c-81ff0191ec35.html","2015-10-28 17:22:11 -0400","DDI-clinical-trial","evidence-supports",", metoprolol , atomoxetine ) ","In vitro studies showed minimal inhibitory effect of desvenlafaxine on CYP2D6. Clinical studies have shown that desvenlafaxine does not have a clinically relevant effect on CYP2D6 metabolism at the dose of 100 mg daily. When desvenlafaxine succinate was administered at a dose of 100 mg daily in conjunction with a single 50 mg dose of desipramine, a CYP2D6 substrate, the Cmax and AUC of desipramine increased approximately 25% and 17%, respectively. When 400 mg (8 times the recommended 50 mg dose) was administered, the Cmax and AUC of desipramine increased approximately 50% and 90%, respectively. Concomitant use of desvenlafaxine with a drug metabolized by CYP2D6 can result in higher concentrations of that drug [see Drug Interactions (7.5)].","","ncit:positive","ncit:quantitative",,"desipramine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","400","desvenlafaxine succinate","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","SD","Oral","1","Daily","Oral","Unk","Unk","90","Percent","Increase","Unk","UNK","UNK","50","Percent","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1809bcb4-5fcc-45ca-986a-4fa5edcd4b5e.html","2015-10-29 11:26:06 -0400","drug-drug-interaction","evidence-supports","","Co-administration of haloperidol with CMI increases plasma concentrations of CMI. ","Co-administration of","ncit:positive","ncit:Qualitative",,"CMI","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction",,"haloperidol","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-10-29 11:30:54 -0400","drug-drug-interaction","evidence-supports","","Concurrent administration of cimetidine and tricyclic antidepressants can produce clinically significant increases in the plasma concentrations of the tricyclic antidepressants."," Conversely, decreases in plas","ncit:positive","ncit:Qualitative",,"tricyclic antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1809bcb4-5fcc-45ca-986a-4fa5edcd4b5e.html","2015-09-29 09:58:27 -0400","drug-drug-interaction","evidence-supports","er tricyclic antidepressants. ","The plasma concentration of CMI has been reported to be increased by the concomitant administration of haloperidol; plasma levels of several closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of methylphenidate or hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by the concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin), and such an effect may be anticipated with CMI as well. Administration of CMI has been reported to increase the plasma levels of phenobarbital, if given concomitantly (see CLINICAL PHARMACOLOGY, Interactions).","","ncit:positive","ncit:Qualitative",,"fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","tricyclic antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:13:55 -0400","DDI-clinical-trial","evidence-supports","","Olanzapine In subjects who had received EMSAM 6 mg per 24 hours for 10 days, co-administration with olanzapine, a substrate for CYP1A2, CYP2D6, and possibly CYP2A6, did not affect the pharmacokinetics of selegiline or olanzapine [see Drug Interactions (7.4) and (7.5)].","","ncit:negative","ncit:quantitative",,"olanzapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","EMSAM","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","6","UNK","UNK","Unk","Daily","transdermal","10","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","ed in healthy adult subjects. ","Carbamazepine-There were no clinically significant changes in the pharmacokinetics of milnacipran following co-administration of Savella (100 mg/day) and carbamazepine (200 mg twice a day). No changes were observed in the pharmacokinetics of carbamazepine or its epoxide metabolite due to co-administration with Savella. ","","ncit:negative","ncit:quantitative",,"carbamazepine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","milnacipran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","200","Daily","tablet","Unk","BID","tablet","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:43:54 -0400","drug-drug-interaction","evidence-supports","AUBAGIO on CYP1A2 substrates ","Teriflunomide may be a weak inducer of CYP1A2 in vivo. In patients taking AUBAGIO, exposure of drugs metabolized by CYP1A2 (e.g., alosetron, duloxetine, theophylline, tizanidine) may be reduced. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP1A2 as required [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","theophylline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","atment switch is recommended. ","Digoxin-There was no pharmacokinetic interaction between Savella (200 mg/day) and digoxin (0.2 mg/day Lanoxicaps) following multiple-dose administration to healthy subjects. ","","ncit:negative","ncit:quantitative",,"digoxin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","0.2","Savella","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","200","Daily","tablet","Unk","Daily","tablet","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:38:35 -0500","DDI-clinical-trial","evidence-supports","","Pimozide - In a controlled study, a single dose of pimozide 2 mg co-administered with citalopram 40 mg given once daily for 11 days was associated with a mean increase in QTc values of approximately 10 msec compared to pimozide given alone. Citalopram did not alter the mean AUC or Cmax of pimozide. The mechanism of this pharmacodynamic interaction is not known.","","ncit:negative","ncit:quantitative",,"citalopram","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","pimozide","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","2","SD","Oral","1","Daily","Oral","11","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:48:50 -0400","drug-drug-interaction","evidence-supports","nsporter 3 (OAT3) substrates ","Teriflunomide inhibits the activity of OAT3 in vivo. In patients taking AUBAGIO, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) which are OAT3 substrates as required [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"ciprofloxacin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c66a11c1-3093-45ef-b348-3b196c05ba0c.html","2015-10-01 10:31:02 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dosage regimen of a TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:32:33 -0500","drug-drug-interaction","evidence-supports","ss this question are limited. ","CYP3A4 and CYP 2C19 inhibitors: Since CYP3A4 and CYP 2C19 are the primary enzymes involved in the metabolism of citalopram, it is expected that potent inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, and macrolide antibiotics) and potent inhibitors of CYP2C19 (e.g., omeprazole) might decrease the clearance of citalopram. However, coadministration of citalopram and the potent CYP3A4 inhibitor ketoconazole did not significantly affect the pharmacokinetics of citalopram. Celexa 20 mg/day is the maximum recommended dose in patients taking concomitant cimetidine or another CYP2C19 inhibitor, because of the risk of QT prolongation (see WARNINGS and DOSAGE AND ADMINISTRATION).","","ncit:negative","ncit:Qualitative",,"ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","citalopram","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1809bcb4-5fcc-45ca-986a-4fa5edcd4b5e.html","2015-09-29 09:58:27 -0400","drug-drug-interaction","evidence-supports","er tricyclic antidepressants. ","The plasma concentration of CMI has been reported to be increased by the concomitant administration of haloperidol; plasma levels of several closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of methylphenidate or hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by the concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin), and such an effect may be anticipated with CMI as well. Administration of CMI has been reported to increase the plasma levels of phenobarbital, if given concomitantly (see CLINICAL PHARMACOLOGY, Interactions).","","ncit:positive","ncit:Qualitative",,"barbiturates","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction","","tricyclic antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-10-28 15:26:32 -0400","DDI-clinical-trial","evidence-supports","","The effect of paroxetine on the pharmacokinetics of atomoxetine has been evaluated when both drugs were at steady state. In healthy volunteers who were extensive metabolizers of CYP2D6, paroxetine 20 mg daily was given in combination with 20 mg atomoxetine every 12 hours. This resulted in increases in steady state atomoxetine AUC values that were 6- to 8-fold greater and in atomoxetine Cmax values that were 3- to 4-fold greater than when atomoxetine was given alone. Dosage adjustment of atomoxetine may be necessary and it is recommended that atomoxetine be initiated at a reduced dose when it is given with paroxetine.","","ncit:positive","ncit:quantitative",,"paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","atomoxetine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","20","Q12","Oral","Unk","Daily","Oral","Unk","Unk","6-8","Fold","Increase","Unk","UNK","UNK","3-4","Fold","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:43:54 -0400","drug-drug-interaction","evidence-supports","AUBAGIO on CYP1A2 substrates ","Teriflunomide may be a weak inducer of CYP1A2 in vivo. In patients taking AUBAGIO, exposure of drugs metabolized by CYP1A2 (e.g., alosetron, duloxetine, theophylline, tizanidine) may be reduced. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP1A2 as required [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","duloxetine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:36:27 -0400","DDI-clinical-trial","evidence-supports","dDOSAGE AND ADMINISTRATION . ","Drugs Metabolized by P450 3A4–In three separate in vivo interaction studies, sertraline was co-administered with cytochrome P450 3A4 substrates, terfenadine, carbamazepine, or cisapride under steady-state conditions. The results of these studies indicated that sertraline did not increase plasma concentrations of terfenadine, carbamazepine, or cisapride. These data indicate that sertraline’s extent of inhibition of P450 3A4 activity is not likely to be of clinical significance. Results of the interaction study with cisapride indicate that sertraline 200 mg (q.d.) induces the metabolism of cisapride (cisapride AUC and Cmax were reduced by about 35%).","","ncit:negative","ncit:quantitative",,"sertraline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","terfenadine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ea35caf8-c8c8-481a-97a2-25f68cbc240b.html","2015-09-29 09:04:36 -0400","drug-drug-interaction","evidence-supports","e in plasma AUC of the TCA ). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"propafenone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c3ca69e6-1ea0-4c2c-abcb-7264b2e79a87.html","2015-10-29 10:29:25 -0400","drug-drug-interaction","evidence-supports","ients receiving maprotiline . ","Because of the pharmacologic similarity of maprotiline hydrochloride to the tricyclic antidepressants, the plasma concentration of maprotiline may be increased when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), as has occurred with tricyclic antidepressants. Adjustment of the dosage of maprotiline hydrochloride may therefore be necessary in such cases.","","ncit:positive","ncit:Qualitative",,"fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"maprotiline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-10-29 11:30:54 -0400","drug-drug-interaction","evidence-supports","","Certain drugs, particularly the psychostimulants and the phenothiazines, increase plasma levels of concomitantly administered tricyclic antidepressants through competition for the same metabolic enzyme systems. ","Concurrent administration of","ncit:positive","ncit:Qualitative",,"psychostimulants","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction",,"tricyclic antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/55816042-946d-4bec-9461-bd998628ff45.html","2015-10-14 11:57:06 -0400","drug-drug-interaction","evidence-supports","tantly administered rifampin. ","Rifampin has been reported to substantially decrease the plasma concentrations of the following antiviral drugs: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir. These antiviral drugs must not be co-administered with rifampin. (See CONTRAINDICATIONS.) ","","ncit:positive","ncit:Qualitative",,"darunavir","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Rifampin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a9ff32c4-3bcf-4e51-ae8c-81ff0191ec35.html","2015-10-28 17:22:13 -0400","DDI-clinical-trial","evidence-supports","ized by CYP3A4 ( midazolam ) ","In vitro, desvenlafaxine does not inhibit or induce the CYP3A4 isozyme. In a clinical study, desvenlafaxine 400 mg daily (8 times the recommended 50 mg dose) was co-administered with a single 4 mg dose of midazolam (a CYP3A4 substrate). The AUC and Cmax of midazolam decreased by approximately 31% and 16%, respectively. Concomitant use of desvenlafaxine with a drug metabolized by CYP3A4 can result in lower exposures to that drug. ","","ncit:positive","ncit:quantitative",,"midazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","4","desvenlafaxine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","400","SD","Oral","1","Daily","Oral","Unk","Unk","31","Percent","Decrease","Unk","UNK","UNK","16","Percent","Decrease","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:48:13 -0400","DDI-clinical-trial","evidence-supports"," Lithium ","No relevant clinical effects or significant changes in pharmacokinetics have been observed in healthy male subjects on concurrent treatment with subtherapeutic levels of lithium (600 mg/day for 10 days) at steady state and a single 30-mg dose of mirtazapine. The effects of higher doses of lithium on the pharmacokinetics of mirtazapine are unknown.","","ncit:negative","ncit:quantitative",,"mirtazapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","30","lithium","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","SD","Oral","1","Daily","Oral","10","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","stration to healthy subjects. ","Fluoxetine-Switching from fluoxetine (20 mg once a day), a strong inhibitor of CYP2D6 and a moderate inhibitor of CYP2C19, to milnacipran (100 mg/day) without a washout period did not affect the pharmacokinetics of milnacipran. ","","ncit:negative","ncit:quantitative",,"fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","milnacipran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","20","Daily","tablet","Unk","Daily","tablet","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-09-29 11:28:40 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type IC antiarrhythmics propafenone and flecainide). While all the SSRIs, e.g., fluoxetine, sertraline, paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","flecainide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"quinidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 14:01:28 -0500","DDI-clinical-trial","evidence-supports","","Imipramine and Other Tricyclic Antidepressants (TCAs) - In vitro studies suggest that citalopram is a relatively weak inhibitor of CYP2D6. Coadministration of Celexa (40 mg/day for 10 days) with the TCA imipramine (single dose of 100 mg), a substrate for CYP2D6, did not significantly affect the plasma concentrations of imipramine or citalopram. However, the concentration of the imipramine metabolite desipramine was increased by approximately 50%. The clinical significance of the desipramine change is unknown. Nevertheless, caution is indicated in the coadministration of TCAs with Celexa.","","ncit:negative","ncit:quantitative",,"Imipramine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","citalopram","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","40","Daily","Oral","10","SD","Oral","1","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f356c1b-96bd-4ef1-960c-91cf4905e6b1.html","2015-09-10 14:36:47 -0400","drug-drug-interaction","evidence-supports","","Anticonvulsants — Patients on stable doses of phenytoin and carbamazepine have developed elevated plasma anticonvulsant concentrations and clinical anticonvulsant toxicity following initiation of concomitant fluoxetine treatment.","","ncit:positive","ncit:Qualitative",,"carbamazepine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","DDI-clinical-trial","evidence-supports","RP and OATP1B1/1B3 Substrates ","There was an increase in mean rosuvastatin Cmax and AUC (2.65- and 2.51-fold, respectively), following repeated doses of teriflunomide , suggesting that teriflunomide is an inhibitor of BCRP transporter and organic anion transporting polypeptide 1B1 and 1B3 (OATP1B1/1B3) [see Drug Interactions (7)].","","ncit:positive","ncit:quantitative",,"rosuvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","2.51","Fold","Increase","Unk","UNK","UNK","2.65","Fold","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:38:24 -0400","drug-drug-interaction","evidence-supports","AUBAGIO on CYP2C8 substrates ","Teriflunomide is an inhibitor of CYP2C8 in vivo. In patients taking AUBAGIO, exposure of drugs metabolized by CYP2C8 (e.g., paclitaxel, pioglitazone, repaglinide, rosiglitazone) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP2C8 as required [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"rosiglitazone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 12:53:42 -0400","drug-drug-interaction","evidence-supports"," B3 (OATP1B1/1B3) substrates ","Teriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo. For a patient taking AUBAGIO, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking AUBAGIO [see Clinical Pharmacology (12.3)]","","ncit:positive","ncit:Qualitative",,"Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","rosuvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/829a4f51-c882-4b64-81f3-abfb03a52ebe.html","2015-10-29 09:30:25 -0400","DDI-clinical-trial","evidence-supports"," 7.2 Inhibitors of CYP2D6 ","Concomitant use of duloxetine (40 mg once daily) with paroxetine (20 mg once daily) increased the concentration of duloxetine AUC by about 60%, and greater degrees of inhibition are expected with higher doses of paroxetine. Similar effects would be expected with other potent CYP2D6 inhibitors (e.g., fluoxetine, quinidine) [see WARNINGS AND PRECAUTIONS (5.12)]. ","","ncit:positive","ncit:quantitative",,"paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","duloxetine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","40","Daily","Oral","Unk","Daily","Oral","Unk","Unk","50","Percent","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a9ff32c4-3bcf-4e51-ae8c-81ff0191ec35.html","2015-10-28 17:17:45 -0400","DDI-clinical-trial","evidence-supports","CYP3A4 substrates (Figure 2). ","Clinical studies have shown that desvenlafaxine (100 mg daily) does not have a clinically relevant effect on tamoxifen and aripiprazole, compounds that are metabolized by a combination of both CYP2D6 and CYP3A4 enzymes (Figure 2).","","ncit:negative","ncit:quantitative",,"desvenlafaxine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","tamoxifen","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","Daily","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:43:54 -0400","drug-drug-interaction","evidence-supports","AUBAGIO on CYP1A2 substrates ","Teriflunomide may be a weak inducer of CYP1A2 in vivo. In patients taking AUBAGIO, exposure of drugs metabolized by CYP1A2 (e.g., alosetron, duloxetine, theophylline, tizanidine) may be reduced. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP1A2 as required [see Clinical Pharmacology (12.3)]","","ncit:positive","ncit:Qualitative",,"Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","tizanidine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:43:54 -0400","drug-drug-interaction","evidence-supports","BAGIO on oral contraceptives ","AUBAGIO may increase the systemic exposures of ethinylestradiol and levonorgestrel. Consideration should be given to the type or dose of contraceptives used in combination with AUBAGIO [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"AUBAGIO","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","ethinylestradiol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","0 mg) and lorazepam (1.5 mg). ","Pregabalin-There were no clinically significant changes in the steady-state pharmacokinetics of milnacipran or pregabalin following twice a day co-administration of 50 mg milnacipran and 150 mg pregabalin. ","","ncit:negative","ncit:quantitative",,"milnacipran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","50","pregabalin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","150","BID","tablet","Unk","BID","tablet","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c66a11c1-3093-45ef-b348-3b196c05ba0c.html","2015-10-01 10:31:02 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dosage regimen of a TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","flecainide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:33:30 -0500","DDI-clinical-trial","evidence-supports"," 7.16 Ketoconazole ","Combined administration of racemic citalopram (40 mg) and ketoconazole (200 mg), a potent CYP3A4 inhibitor, decreased the Cmax and AUC of ketoconazole by 21% and 10%, respectively, and did not significantly affect the pharmacokinetics of citalopram. ","","ncit:negative","ncit:quantitative",,"citalopram","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","40","ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","UNK","Oral","Unk","UNK","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 14:00:45 -0500","DDI-clinical-trial","evidence-supports","","Ketoconazole - Combined administration of Celexa (40 mg) and ketoconazole (200 mg) decreased the Cmax and AUC of ketoconazole by 21% and 10%, respectively, and did not significantly affect the pharmacokinetics of citalopram.","","ncit:negative","ncit:quantitative",,"citalopram","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","40","ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","UNK","Oral","Unk","UNK","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ea35caf8-c8c8-481a-97a2-25f68cbc240b.html","2015-09-29 09:04:36 -0400","drug-drug-interaction","evidence-supports","e in plasma AUC of the TCA ). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 12:50:04 -0400","drug-drug-interaction","evidence-supports"," B3 (OATP1B1/1B3) substrates ","Teriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo. For a patient taking AUBAGIO, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking AUBAGIO [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","mitoxantrone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a9ff32c4-3bcf-4e51-ae8c-81ff0191ec35.html","2015-10-28 17:17:46 -0400","DDI-clinical-trial","evidence-supports","CYP3A4 substrates (Figure 2). ","Clinical studies have shown that desvenlafaxine (100 mg daily) does not have a clinically relevant effect on tamoxifen and aripiprazole, compounds that are metabolized by a combination of both CYP2D6 and CYP3A4 enzymes (Figure 2).","","ncit:negative","ncit:quantitative",,"desvenlafaxine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","aripiprazole","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","Daily","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:35:24 -0400","DDI-clinical-trial","evidence-supports"," Carbamazepine ","In healthy male patients (n=24), carbamazepine (400 mg b.i.d.) increased mirtazapine (15 mg b.i.d.) clearance about 2-fold, resulting in a decrease in average plasma mirtazapine concentrations of 60%. When phenytoin, carbamazepine, or another inducer of hepatic metabolism (such as rifampicin) is added to mirtazapine therapy, the mirtazapine dose may have to be increased. If treatment with such a medicinal product is discontinued, it may be necessary to reduce the mirtazapine dose.","","ncit:positive","ncit:quantitative",,"mirtazapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","15","carbamazepine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","400","BID","Oral","Unk","BID","Oral","Unk","24","Unk","UNK","UNK","2","Fold","Increase","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/cc9e1c8c-0e2b-44e2-878b-27057f786be9.html","2015-08-20 13:53:28 -0400","DDI-clinical-trial","evidence-supports","ions (5.1)] . Ketoconazole ","The blood levels of fingolimod and fingolimod-phosphate are increased by 1.7-fold when used concomitantly with ketoconazole. Patients who use GILENYA and systemic ketoconazole concomitantly should be closely monitored, as the risk of adverse reactions is greater.","","ncit:positive","ncit:quantitative",,"fingolimod","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","1.7","Fold","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/7c295b64-ec39-42ec-9f02-da5b42e775e1.html","2015-08-20 10:29:59 -0400","drug-drug-interaction","evidence-supports","","Clinical studies have not shown any drug interactions between bicalutamide and LHRH analogs (goserelin or leuprolide). There is no evidence that bicalutamide induces hepatic enzymes","","ncit:negative","ncit:Qualitative",,"leuprolide","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","bicalutamide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:35:22 -0500","DDI-clinical-trial","evidence-supports"," 7.17 Ritonavir ","Combined administration of a single dose of ritonavir (600 mg), both a CYP3A4 substrate and a potent inhibitor of CYP3A4, and escitalopram (20 mg) did not affect the pharmacokinetics of either ritonavir or escitalopram. ","","ncit:negative","ncit:quantitative",,"escitalopram","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","ritonavir","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","600","UNK","Oral","Unk","UNK","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:22:34 -0500","DDI-clinical-trial","evidence-supports"," 7.7 Cimetidine ","In subjects who had received 21 days of 40 mg/day racemic citalopram, combined administration of 400 mg twice a day cimetidine for 8 days resulted in an increase in citalopram AUC and Cmax of 43% and 39%, respectively. The clinical significance of these findings is unknown. ","","ncit:positive","ncit:quantitative",,"cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","400","citalopram","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","40","Daily","Oral","21","BID","Oral","8","Unk","43","Percent","Increase","Unk","UNK","UNK","39","Percent","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","DDI-clinical-trial","evidence-supports","(7) ] . Oral Contraceptives ","There was an increase in mean ethinylestradiol Cmax and AUC0–24 (1.58- and 1.54-fold, respectively) and levonorgestrel Cmax and AUC0–24 (1.33- and 1.41-fold, respectively) following repeated doses of teriflunomide [see Drug Interactions (7)].","","ncit:positive","ncit:quantitative",,"teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","ethinylestradiol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","1.54","Fold","Increase","Unk","UNK","UNK","1.58","Fold","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-09-29 11:28:40 -0400","drug-drug-interaction","evidence-supports","0","Other substances, particularly barbiturates and alcohol, induce liver enzyme activity and thereby reduce tricyclic antidepressant plasma levels. Similar effects have been reported with tobacco smoke.","","ncit:positive","ncit:Qualitative",,"barbiturates","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction","","tricyclic antidepressant","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a16297df-3158-48db-85e5-5cd506885556.html","2015-09-29 09:27:10 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine, cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c66a11c1-3093-45ef-b348-3b196c05ba0c.html","2015-10-29 11:36:34 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dosage regimen of a TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction",,"SSRIs","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ea35caf8-c8c8-481a-97a2-25f68cbc240b.html","2015-09-29 09:04:36 -0400","drug-drug-interaction","evidence-supports","e in plasma AUC of the TCA ). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:41:13 -0400","drug-drug-interaction","evidence-supports"," Ketoconazole ","In healthy, male, Caucasian patients (n=24), coadministration of the potent CYP3A4 inhibitor ketoconazole (200 mg b.i.d. for 6.5 days) increased the peak plasma levels and the AUC of a single 30-mg dose of mirtazapine by approximately 40% and 50%, respectively. Caution should be exercised when coadministering mirtazapine with potent CYP3A4 inhibitors, HIV protease inhibitors, azole antifungals, erythromycin, or nefazodone.","","ncit:positive","ncit:Qualitative",,"mirtazapine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"azole antifungals","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:02:39 -0500","DDI-clinical-trial","evidence-supports","","In a healthy volunteer study, ritonavir 100 mg twice daily reduced the AUC and Cmax of bupropion by 22% and 21%, respectively. The exposure of the hydroxybupropion metabolite was decreased by 23%, the threohydrobupropion decreased by 38%, and the erythrohydrobupropion decreased by 48%. ","In a second healthy volunteer study,","ncit:positive","ncit:quantitative",,"bupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","ritonavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","UNK","UNK","Unk","BID","Oral","Unk","Unk","22","Percent","Decrease","Unk","UNK","UNK","21","Percent","Decrease","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e17dc299-f52d-414d-ab6e-e809bd6f8acb.html","2015-11-04 14:14:49 -0500","drug-drug-interaction","evidence-supports","(TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","flecainide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports"," Drugs Metabolized by CYP2D6 ","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","","ncit:positive","ncit:Qualitative",,"Bupropion","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"metoprolol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e17dc299-f52d-414d-ab6e-e809bd6f8acb.html","2015-11-04 14:14:49 -0500","drug-drug-interaction","evidence-supports","(TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:13:14 -0500","DDI-clinical-trial","evidence-supports","erythrohydrobupropion decreased by 68%. ","In another healthy volunteer study, lopinavir 400 mg/ritonavir 100 mg twice daily decreased bupropion AUC and Cmax by 57%. The AUC and Cmax of hydroxybupropion metabolite were decreased by 50% and 31%, respectively.","","ncit:positive","ncit:quantitative",,"ritonavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","hydroxybupropion","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","BID","Oral","Unk","Unk","50","Percent","Decrease","Unk","UNK","UNK","31","Percent","Decrease","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:20:54 -0400","DDI-clinical-trial","evidence-supports"," Diazepam ","The coadministration of fluvoxamine maleate tablets and diazepam is generally not advisable. Because fluvoxamine reduces the clearance of both diazepam and its active metabolite, N-desmethyldiazepam, there is a strong likelihood of substantial accumulation of both species during chronic coadministration. Evidence supporting the conclusion that it is inadvisable to coadminister fluvoxamine and diazepam is derived from a study in which healthy volunteers taking 150 mg/day of fluvoxamine were administered a single oral dose of 10 mg of diazepam. In these subjects (N = 8), the clearance of diazepam was reduced by 65% and that of N-desmethyldiazepam to a level that was too low to measure over the course of the 2 week long study. It is likely that this experience significantly underestimates the degree of accumulation that might occur with repeated diazepam administration. Moreover, as noted with alprazolam, the effect of fluvoxamine may even be more pronounced when it is administered at higher doses. Accordingly, diazepam and fluvoxamine should not ordinarily be coadministered. ","","ncit:positive","ncit:quantitative",,"N-desmethyldiazepam","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","Unk","fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","150","UNK","UNK","Unk","Daily","Oral","Unk","8","Unk","UNK","UNK","unmeasurable","UNK","Decrease","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e17dc299-f52d-414d-ab6e-e809bd6f8acb.html","2015-11-04 14:10:24 -0500","drug-drug-interaction","evidence-challenges","","Concurrent administration of cimetidine and tricyclic antidepressants can produce clinically significant increases in the plasma concentrations of the tricyclic antidepressant."," The patient should be informed that the response to alcohol may be exaggerated","ncit:positive","ncit:Qualitative",,"cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"tricyclic antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:41:13 -0400","drug-drug-interaction","evidence-supports"," Ketoconazole ","In healthy, male, Caucasian patients (n=24), coadministration of the potent CYP3A4 inhibitor ketoconazole (200 mg b.i.d. for 6.5 days) increased the peak plasma levels and the AUC of a single 30-mg dose of mirtazapine by approximately 40% and 50%, respectively. Caution should be exercised when coadministering mirtazapine with potent CYP3A4 inhibitors, HIV protease inhibitors, azole antifungals, erythromycin, or nefazodone.","","ncit:positive","ncit:Qualitative",,"mirtazapine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"HIV protease inhibitors","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","metabolism have not been studied. ","A clinically significant fluvoxamine interaction is possible with drugs having a narrow therapeutic ratio such as pimozide, warfarin, theophylline, certain benzodiazepines, omeprazole and phenytoin. If fluvoxamine maleate tablets are to be administered together with a drug that is eliminated via oxidative metabolism and has a narrow therapeutic window, plasma levels and/or pharmacodynamic effects of the latter drug should be monitored closely, at least until steady-state conditions are reached [see Contraindications (4) and Warnings and Precautions (5)]. ","","ncit:positive","ncit:Qualitative",,"fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"phenytoin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:37:50 -0500","DDI-clinical-trial","evidence-supports"," Alprazolam ","When alprazolam (1 mg BID) and nefazodone (200 mg BID) were coadministered, steady-state peak concentrations, AUC and half-life values for alprazolam increased by approximately 2 fold. Nefazodone plasma concentrations were unaffected by alprazolam. If alprazolam is coadministered with nefazodone, a 50% reduction in the initial alprazolam dosage is recommended. No dosage adjustment is required for nefazodone.","","ncit:positive","ncit:quantitative",,"nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","alprazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","1","SD","Oral","1","BID","Oral","Unk","Unk","2","Fold","Increase","Unk","UNK","UNK","Unk","UNK","UNK","2","Fold","Increase" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:27:20 -0500","drug-drug-interaction","evidence-supports","Clinical Pharmacology (12.3) ]. Inducers of CYP2B6 ","Ritonavir, Lopinavir, and Efavirenz: Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure. Dosage increase of WELLBUTRIN XL may be necessary when coadministered with ritonavir, lopinavir, or efavirenz but should not exceed the maximum recommended dose [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"Lopinavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"hydroxybupropion","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 14:25:13 -0400","DDI-clinical-trial","evidence-supports","5.7 Potential Alosetron Interaction ","Because alosetron is metabolized by a variety of hepatic CYP drug metabolizing enzymes, inducers or inhibitors of these enzymes may change the clearance of alosetron. Fluvoxamine is a known potent inhibitor of CYP1A2 and also inhibits CYP3A4, CYP2C9, and CYP2C19. In a pharmacokinetic study, 40 healthy female subjects received fluvoxamine in escalating doses from 50 mg to 200 mg a day for 16 days, with coadministration of alosetron 1 mg on the last day. Fluvoxamine increased mean alosetron plasma concentration (AUC) approximately 6-fold and prolonged the half-life by approximately 3-fold [see Contraindications (4.1)] and Lotronex™† (alosetron) package insert. ","","ncit:positive","ncit:quantitative",,"Fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","50 to 200","alosetron","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","1","SD","Oral","1","Daily","Oral","16","40","6","Fold","Increase","Unk","UNK","UNK","Unk","UNK","UNK","3","Fold","Increase" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:43:14 -0500","DDI-clinical-trial","evidence-supports"," Alprazolam ","When alprazolam (1 mg BID) and nefazodone (200 mg BID) were coadministered, steady-state peak concentrations, AUC and half-life values for alprazolam increased by approximately 2 fold. Nefazodone plasma concentrations were unaffected by alprazolam. If alprazolam is coadministered with nefazodone, a 50% reduction in the initial alprazolam dosage is recommended. No dosage adjustment is required for nefazodone.","","ncit:negative","ncit:quantitative",,"nefazodone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","200","alprazolam","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","1","BID","Oral","Unk","SD","Oral","1","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:36:55 -0500","DDI-clinical-trial","evidence-supports"," Triazolam ","When a single oral 0.25 mg dose of triazolam was coadministered with nefazodone (200 mg BID) at steady state, triazolam half-life and AUC increased 4 fold and peak concentrations increased 1.7 fold. Nefazodone plasma concentrations were unaffected by triazolam. Coadministration of nefazodone potentiated the effects of triazolam on psychomotor performance tests. If triazolam is coadministered with nefazodone, a 75% reduction in the initial triazolam dosage is recommended. Because not all commercially available dosage forms of triazolam permit sufficient dosage reduction, coadministration of triazolam with nefazodone should be avoided for most patients, including the elderly. In the exceptional case where coadministration of triazolam with nefazodone may be considered appropriate, only the lowest possible dose of triazolam should be used (see CONTRAINDICATIONS and PRECAUTIONS).","","ncit:positive","ncit:quantitative",,"triazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","0.25","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","SD","Oral","1","BID","Oral","Unk","Unk","4","Fold","Increase","Unk","UNK","UNK","1.7","Fold","Increase","4","Fold","Increase" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:42:05 -0500","DDI-clinical-trial","evidence-supports","Potential for Other Drugs to Affect WELLBUTRIN XL ","In vitro studies indicate that bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists for drug interactions between WELLBUTRIN XL and drugs that are inhibitors or inducers of CYP2B6. In addition, in vitro studies suggest that paroxetine, sertraline, norfluoxetine, fluvoxamine, and nelfinavir, inhibit the hydroxylation of bupropion.","","ncit:positive","ncit:quantitative",,"norfluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","bupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b8881a81-75d7-43e8-825f-37c352c146dc.html","2015-11-04 14:19:06 -0500","drug-drug-interaction","evidence-supports","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquine hydroxylase) is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small or quite large (8 fold increase in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics, propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction",,"cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:13:14 -0500","DDI-clinical-trial","evidence-supports","erythrohydrobupropion decreased by 68%. ","In another healthy volunteer study, lopinavir 400 mg/ritonavir 100 mg twice daily decreased bupropion AUC and Cmax by 57%. The AUC and Cmax of hydroxybupropion metabolite were decreased by 50% and 31%, respectively.","","ncit:positive","ncit:quantitative","Combined lopinavir/ritonavir dose","lopinavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","400","bupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","BID","Oral","Unk","Unk","57","Percent","Decrease","Unk","UNK","UNK","57","Percent","Decrease","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e17dc299-f52d-414d-ab6e-e809bd6f8acb.html","2015-11-04 14:14:49 -0500","drug-drug-interaction","evidence-supports","(TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","sertraline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/0177d783-773c-41bf-9db9-eb7e5c64474a.html","2015-11-05 10:40:12 -0500","drug-drug-interaction","evidence-supports","Drugs Metabolized by P450 2D6 ","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7-10% of caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of the isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.","","ncit:positive","ncit:Qualitative",,"fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"tricyclic antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/0177d783-773c-41bf-9db9-eb7e5c64474a.html","2015-11-05 10:40:12 -0500","drug-drug-interaction","evidence-supports","Drugs Metabolized by P450 2D6 ","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7-10% of caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of the isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.","","ncit:positive","ncit:Qualitative",,"SSRIs","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction",,"tricyclic antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports"," Drugs Metabolized by CYP2D6 ","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","","ncit:positive","ncit:Qualitative",,"paroxetine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Bupropion","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports"," Drugs Metabolized by CYP2D6 ","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","","ncit:positive","ncit:Qualitative",,"Bupropion","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"flecainide","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:46:57 -0500","DDI-clinical-trial","evidence-supports"," Inhibitors of CYP2B6 ","Ticlopidine, Clopidogrel: In a study in healthy male volunteers, clopidogrel 75 mg once daily or ticlopidine 250 mg twice daily increased exposures (Cmax and AUC) of bupropion by 40% and 60% for clopidogrel, by 38% and 85% for ticlopidine, respectively. The exposures of hydroxybupropion were decreased. ","","ncit:positive","ncit:quantitative",,"bupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","clopidogrel","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","75","UNK","UNK","Unk","Daily","Oral","Unk","Unk","60","Percent","Increase","Unk","UNK","UNK","40","Percent","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:53:54 -0500","DDI-clinical-trial","evidence-supports","and AUC values of hydroxybupropion by 32% and 24%, respectively. ","Cimetidine: Following oral administration of bupropion 300 mg with and without cimetidine 800 mg in 24 healthy young male volunteers, the pharmacokinetics of bupropion and hydroxybupropion were unaffected. However, there were 16% and 32% increases in the AUC and Cmax, respectively, of the combined moieties of threohydrobupropion and erythrohydrobupropion.","","ncit:positive","ncit:quantitative","Combined moieties of threohydrobupropion and erythrohydrobupropion","threohydrobupropion and erythrohydrobupropion","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","Unk","bupropion","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","800","UNK","UNK","Unk","UNK","Oral","Unk","24","16","Percent","Increase","Unk","UNK","UNK","32","Percent","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/0177d783-773c-41bf-9db9-eb7e5c64474a.html","2015-11-05 10:40:12 -0500","drug-drug-interaction","evidence-supports","Drugs Metabolized by P450 2D6 ","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7-10% of caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of the isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.","","ncit:positive","ncit:Qualitative",,"antidepressants","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction",,"tricyclic antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:43:14 -0500","drug-drug-interaction","evidence-supports","Potential Terfenadine, Astemizole, Cisapride, and Pimozide Interactions ","Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. Increased plasma concentrations of terfenadine, astemizole, cisapride, and pimozide are associated with QT prolongation and with rare cases of serious cardiovascular adverse events, including death, due principally to ventricular tachycardia of the torsade de pointes type. Nefazodone has been shown in vitro to be an inhibitor of CYP3A4. Consequently, it is recommended that nefazodone not be used in combination with either terfenadine, astemizole, cisapride, or pimozide (see CONTRAINDICATIONS and PRECAUTIONS).","","ncit:positive","ncit:Qualitative",,"nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"terfenadine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:46:57 -0500","DDI-clinical-trial","evidence-supports"," Inhibitors of CYP2B6 ","Ticlopidine, Clopidogrel: In a study in healthy male volunteers, clopidogrel 75 mg once daily or ticlopidine 250 mg twice daily increased exposures (Cmax and AUC) of bupropion by 40% and 60% for clopidogrel, by 38% and 85% for ticlopidine, respectively. The exposures of hydroxybupropion were decreased. ","","ncit:positive","ncit:quantitative",,"ticlopidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","250","bupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","BID","Oral","Unk","Unk","85","Percent","Increase","Unk","UNK","UNK","38","Percent","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports"," Drugs Metabolized by CYP2D6 ","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","","ncit:positive","ncit:Qualitative",,"Bupropion","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:29:30 -0400","DDI-clinical-trial","evidence-supports"," Ramelteon ","When fluvoxamine 100 mg twice daily was administered for 3 days prior to single-dose coadministration of ramelteon 16 mg and fluvoxamine, the AUC for ramelteon increased approximately 190-fold and the Cmax increased approximately 70-fold compared to ramelteon administered alone. Ramelteon should not be used in combination with fluvoxamine. ","","ncit:positive","ncit:quantitative",,"fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","ramelteon","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","16","SD","Oral","1","BID","Oral","3","Unk","190","Fold","Increase","Unk","UNK","UNK","70","Fold","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports"," Drugs Metabolized by CYP2D6 ","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","","ncit:positive","ncit:Qualitative",,"Bupropion","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"antipsychotics","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/0177d783-773c-41bf-9db9-eb7e5c64474a.html","2015-11-05 10:40:12 -0500","drug-drug-interaction","evidence-supports","Drugs Metabolized by P450 2D6 ","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7-10% of caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of the isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.","","ncit:positive","ncit:Qualitative",,"tricyclic antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","propafenone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:56:02 -0500","DDI-clinical-trial","evidence-supports","may be necessary when coadministered with nefazodone . ","Lorazepam – When lorazepam (2 mg BID) and nefazodone (200 mg BID) were coadministered to steady state, there was no change in any pharmacokinetic parameter for either drug compared to each drug administered alone. Therefore, dosage adjustment is not necessary for either drug when coadministered.","","ncit:negative","ncit:quantitative",,"lorazepam","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","2","nefazodone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","200","BID","Oral","Unk","BID","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:41:13 -0400","drug-drug-interaction","evidence-supports"," Ketoconazole ","In healthy, male, Caucasian patients (n=24), coadministration of the potent CYP3A4 inhibitor ketoconazole (200 mg b.i.d. for 6.5 days) increased the peak plasma levels and the AUC of a single 30-mg dose of mirtazapine by approximately 40% and 50%, respectively. Caution should be exercised when coadministering mirtazapine with potent CYP3A4 inhibitors, HIV protease inhibitors, azole antifungals, erythromycin, or nefazodone.","","ncit:positive","ncit:Qualitative",,"nefazodone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","mirtazapine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e17dc299-f52d-414d-ab6e-e809bd6f8acb.html","2015-11-04 14:10:24 -0500","drug-drug-interaction","evidence-supports","","Drugs Metabolized by P450 2D6 – The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA).","","ncit:positive","ncit:Qualitative","8 fold plasma concentration increase","debrisoquin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"tricyclic antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e17dc299-f52d-414d-ab6e-e809bd6f8acb.html","2015-11-04 14:14:49 -0500","drug-drug-interaction","evidence-supports","(TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"antidepressants","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b8881a81-75d7-43e8-825f-37c352c146dc.html","2015-11-04 14:21:12 -0500","drug-drug-interaction","evidence-supports","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquine hydroxylase) is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small or quite large (8 fold increase in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics, propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"sertraline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","7.1 Potential Interactions with Drugs that Inhibit or are Metabolized by Cytochrome P450 Isoenzymes ","Multiple hepatic cytochrome P450 isoenzymes are involved in the oxidative biotransformation of a large number of structurally different drugs and endogenous compounds. The available knowledge concerning the relationship of fluvoxamine and the cytochrome P450 isoenzyme system has been obtained mostly from pharmacokinetic interaction studies conducted in healthy volunteers, but some preliminary in vitro data are also available. Based on a finding of substantial interactions of fluvoxamine with certain of these drugs [see later parts of this section and also Warnings and Precautions (5)] and limited in vitro data for CYP3A4, it appears that fluvoxamine inhibits several cytochrome P450 isoenzymes that are known to be involved in the metabolism of other drugs such as: CYP1A2 (e.g., warfarin, theophylline, propranolol, tizanidine), CYP2C9 (e.g., warfarin), CYP3A4 (e.g., alprazolam), and CYP2C19 (e.g., omeprazole). ","","ncit:positive","ncit:Qualitative",,"omeprazole","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:40:32 -0500","drug-drug-interaction","evidence-supports","XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index. ","Drugs that require metabolic activation by CYP2D6 to be effective (e.g., tamoxifen), theoretically could have reduced efficacy when administered concomitantly with inhibitors of CYP2D6 such as bupropion. Patients treated concomitantly with WELLBUTRIN XL and such drugs may require increased doses of the drug [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"tamoxifen","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","bupropion","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:30:13 -0500","drug-drug-interaction","evidence-supports"," Drugs Metabolized by CYP2D6 ","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","","ncit:positive","ncit:Qualitative",,"Bupropion","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"nortriptyline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:36:27 -0400","DDI-clinical-trial","evidence-supports","should be contraindicated (see CONTRAINDICATIONS ). ","Results of a placebo-controlled trial in normal volunteers suggest that chronic administration of sertraline 200 mg/day does not produce clinically important inhibition of phenytoin metabolism. Nonetheless, at this time, it is recommended that plasma phenytoin concentrations be monitored following initiation of sertraline therapy with appropriate adjustments to the phenytoin dose, particularly in patients with multiple underlying medical conditions and/or those receiving multiple concomitant medications.","","ncit:negative","ncit:quantitative",,"sertraline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","phenytoin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:42:42 -0500","DDI-clinical-trial","evidence-supports","Potential for Other Drugs to Affect WELLBUTRIN XL ","In vitro studies indicate that bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists for drug interactions between WELLBUTRIN XL and drugs that are inhibitors or inducers of CYP2B6. In addition, in vitro studies suggest that paroxetine, sertraline, norfluoxetine, fluvoxamine, and nelfinavir, inhibit the hydroxylation of bupropion.","","ncit:positive","ncit:quantitative",,"bupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:45:24 -0500","DDI-clinical-trial","evidence-supports","Interaction With Carbamazepine ","The coadministration of carbamazepine 200 mg BID with nefazodone 200 mg BID, at steady state for both drugs, resulted in almost 95% reductions in AUCs for nefazodone and hydroxynefazodone, likely resulting in insufficient plasma nefazodone and hydroxynefazodone concentrations for achieving an antidepressant effect for nefazodone. Consequently, it is recommended that nefazodone not be used in combination with carbamazepine (see CONTRAINDICATIONS and PRECAUTIONS).","","ncit:positive","ncit:quantitative",,"nefazodone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","200","carbamazepine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","BID","Oral","Unk","BID","Oral","Unk","Unk","95","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:55:58 -0500","DDI-clinical-trial","evidence-supports","."," Citalopram: Citalopram did not affect the pharmacokinetics of bupropion and its three metabolites.","","ncit:negative","ncit:quantitative",,"Citalopram","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","bupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports"," Drugs Metabolized by CYP2D6 ","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","","ncit:positive","ncit:Qualitative",,"Bupropion","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"beta-blockers","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/0177d783-773c-41bf-9db9-eb7e5c64474a.html","2015-11-05 10:40:12 -0500","drug-drug-interaction","evidence-supports","Drugs Metabolized by P450 2D6 ","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7-10% of caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of the isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.","","ncit:positive","ncit:Qualitative",,"flecainide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"tricyclic antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:27:20 -0500","drug-drug-interaction","evidence-supports","Clinical Pharmacology (12.3) ]. Inducers of CYP2B6 ","Ritonavir, Lopinavir, and Efavirenz: Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure. Dosage increase of WELLBUTRIN XL may be necessary when coadministered with ritonavir, lopinavir, or efavirenz but should not exceed the maximum recommended dose [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"hydroxybupropion","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","","ritonavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ea35caf8-c8c8-481a-97a2-25f68cbc240b.html","2015-10-29 11:11:52 -0400","drug-drug-interaction","evidence-supports","Paralytic ileus may occur in patients taking tricyclic antidepressants in combination with anticholinergic type drugs. ","Cimetidine is reported to reduce hepatic metabolism of certain tricyclic antidepressants, thereby delaying elimination and increasing steady-state concentrations of these drugs. Clinically significant effects have been reported with the tricyclic antidepressants when used concomitantly with cimetidine. Increases in plasma levels of tricyclic antidepressants, and in the frequency and severity of side effects, particularly anticholinergic, have been reported when cimetidine was added to the drug regimen. Discontinuation of cimetidine in well controlled patients receiving tricyclic antidepressants and cimetidine may decrease the plasma levels and efficacy of the antidepressants.","","ncit:positive","ncit:Qualitative",,"cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"tricyclic antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:32:38 -0400","DDI-clinical-trial","evidence-supports"," Warfarin ","When fluvoxamine maleate (50 mg t.i.d.) was administered concomitantly with warfarin for 2 weeks, warfarin plasma concentrations increased by 98% and prothrombin times were prolonged. Thus patients receiving oral anticoagulants and fluvoxamine maleate tablets should have their prothrombin time monitored and their anticoagulant dose adjusted accordingly. No dosage adjustment is required for fluvoxamine maleate tablets. ","","ncit:positive","ncit:quantitative","Increased plasma concentration of warfarin","fluvoxamine maleate","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","50","warfarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","14","TID","Oral","14","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","metabolism have not been studied. ","A clinically significant fluvoxamine interaction is possible with drugs having a narrow therapeutic ratio such as pimozide, warfarin, theophylline, certain benzodiazepines, omeprazole and phenytoin. If fluvoxamine maleate tablets are to be administered together with a drug that is eliminated via oxidative metabolism and has a narrow therapeutic window, plasma levels and/or pharmacodynamic effects of the latter drug should be monitored closely, at least until steady-state conditions are reached [see Contraindications (4) and Warnings and Precautions (5)]. ","","ncit:positive","ncit:Qualitative",,"fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"benzodiazepines","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","7.1 Potential Interactions with Drugs that Inhibit or are Metabolized by Cytochrome P450 Isoenzymes ","Multiple hepatic cytochrome P450 isoenzymes are involved in the oxidative biotransformation of a large number of structurally different drugs and endogenous compounds. The available knowledge concerning the relationship of fluvoxamine and the cytochrome P450 isoenzyme system has been obtained mostly from pharmacokinetic interaction studies conducted in healthy volunteers, but some preliminary in vitro data are also available. Based on a finding of substantial interactions of fluvoxamine with certain of these drugs [see later parts of this section and also Warnings and Precautions (5)] and limited in vitro data for CYP3A4, it appears that fluvoxamine inhibits several cytochrome P450 isoenzymes that are known to be involved in the metabolism of other drugs such as: CYP1A2 (e.g., warfarin, theophylline, propranolol, tizanidine), CYP2C9 (e.g., warfarin), CYP3A4 (e.g., alprazolam), and CYP2C19 (e.g., omeprazole). ","","ncit:positive","ncit:Qualitative",,"warfarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:29:30 -0400","drug-drug-interaction","evidence-supports"," Methadone ","Significantly increased methadone (plasma level:dose) ratios have been reported when fluvoxamine maleate was administered to patients receiving maintenance methadone treatment, with symptoms of opioid intoxication in one patient. Opioid withdrawal symptoms were reported following fluvoxamine maleate discontinuation in another patient. ","","ncit:positive","ncit:Qualitative","Increased plasma levels","fluvoxamine maleate","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"methadone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:30:13 -0500","drug-drug-interaction","evidence-supports"," Drugs Metabolized by CYP2D6 ","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","","ncit:positive","ncit:Qualitative",,"Bupropion","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"desipramine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:30:13 -0500","drug-drug-interaction","evidence-supports"," Drugs Metabolized by CYP2D6 ","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","","ncit:positive","ncit:Qualitative",,"imipramine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Bupropion","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:25:55 -0500","drug-drug-interaction","evidence-supports","Clinical Pharmacology (12.3) ]. Inducers of CYP2B6 ","Ritonavir, Lopinavir, and Efavirenz: Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure. Dosage increase of WELLBUTRIN XL may be necessary when coadministered with ritonavir, lopinavir, or efavirenz but should not exceed the maximum recommended dose [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"bupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Lopinavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:27:20 -0500","drug-drug-interaction","evidence-supports","Clinical Pharmacology (12.3) ]. Inducers of CYP2B6 ","Ritonavir, Lopinavir, and Efavirenz: Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure. Dosage increase of WELLBUTRIN XL may be necessary when coadministered with ritonavir, lopinavir, or efavirenz but should not exceed the maximum recommended dose [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"hydroxybupropion","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","","Efavirenz","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:52:07 -0500","DDI-clinical-trial","evidence-supports","and AUC values of hydroxybupropion by 32% and 24%, respectively. ","Cimetidine: Following oral administration of bupropion 300 mg with and without cimetidine 800 mg in 24 healthy young male volunteers, the pharmacokinetics of bupropion and hydroxybupropion were unaffected. However, there were 16% and 32% increases in the AUC and Cmax, respectively, of the combined moieties of threohydrobupropion and erythrohydrobupropion.","","ncit:negative","ncit:quantitative",,"bupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","300","cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","800","UNK","Oral","Unk","UNK","Oral","Unk","24","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b8881a81-75d7-43e8-825f-37c352c146dc.html","2015-11-04 14:21:12 -0500","drug-drug-interaction","evidence-supports","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquine hydroxylase) is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small or quite large (8 fold increase in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics, propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"propafenone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:08:54 -0500","DDI-clinical-trial","evidence-supports","erythrohydrobupropion decreased by 48%. ","In a second healthy volunteer study, ritonavir 600 mg twice daily decreased the AUC and Cmax of bupropion by 66% and 62% respectively. The exposure of the hydroxybupropion metabolite was decreased by 78%, the threohydrobupropion decreased by 50%, and the erythrohydrobupropion decreased by 68%. ","","ncit:positive","ncit:quantitative","Exposure decreased by 68%","ritonavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","erythrohydrobupropion","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","BID","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports"," Drugs Metabolized by CYP2D6 ","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","","ncit:positive","ncit:Qualitative",,"propafenone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Bupropion","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:37:51 -0400","drug-drug-interaction","evidence-supports","max were reduced by about 35%). ","Drugs Metabolized by P450 2D6–Many drugs effective in the treatment of major depressive disorder, e.g., the SSRIs, including sertraline, and most tricyclic antidepressant drugs effective in the treatment of major depressive disorder inhibit the biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase), and, thus, may increase the plasma concentrations of co-administered drugs that are metabolized by P450 2D6. The drugs for which this potential interaction is of greatest concern are those metabolized primarily by 2D6 and which have a narrow therapeutic index, e.g., the tricyclic antidepressant drugs effective in the treatment of major depressive disorder and the Type 1C antiarrhythmics propafenone and flecainide. The extent to which this interaction is an important clinical problem depends on the extent of the inhibition of P450 2D6 by the antidepressant and the therapeutic index of the co-administered drug. There is variability among the drugs effective in the treatment of major depressive disorder in the extent of clinically important 2D6 inhibition, and in fact sertraline at lower doses has a less prominent inhibitory effect on 2D6 than some others in the class. Nevertheless, even sertraline has the potential for clinically important 2D6 inhibition. Consequently, concomitant use of a drug metabolized by P450 2D6 with sertraline may require lower doses than usually prescribed for the other drug. Furthermore, whenever sertraline is withdrawn from co-therapy, an increased dose of the co-administered drug may be required (see Tricyclic Antidepressant Drugs Effective in the Treatment of Major Depressive Disorder under PRECAUTIONS).","","ncit:positive","ncit:Qualitative",,"sertraline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"flecainide","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 14:27:00 -0400","drug-drug-interaction","evidence-supports","","Benzodiazepines metabolized by hepatic oxidation (e.g., alprazolam, midazolam, triazolam, etc.) should be used with caution because the clearance of these drugs is likely to be reduced by fluvoxamine. ","The clearance of benzodiazepines metabolized by glucuronidation (e.g.,","ncit:positive","ncit:Qualitative",,"fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"alprazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:43:18 -0500","DDI-clinical-trial","evidence-supports","Potential for Other Drugs to Affect WELLBUTRIN XL ","In vitro studies indicate that bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists for drug interactions between WELLBUTRIN XL and drugs that are inhibitors or inducers of CYP2B6. In addition, in vitro studies suggest that paroxetine, sertraline, norfluoxetine, fluvoxamine, and nelfinavir, inhibit the hydroxylation of bupropion.","","ncit:positive","ncit:quantitative",,"nelfinavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","bupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 14:23:19 -0400","DDI-clinical-trial","evidence-supports","5.4 Potential Thioridazine Interaction ","The effect of fluvoxamine (25 mg b.i.d. for one week) on thioridazine steady-state concentrations was evaluated in ten male inpatients with schizophrenia. Concentrations of thioridazine and its two active metabolites, mesoridazine and sulforidazine, increased 3-fold following coadministration of fluvoxamine. Thioridazine administration produces a dose-related prolongation of the QTc interval, which is associated with serious ventricular arrhythmias, such as torsades de pointes-type arrhythmias, and sudden death. It is likely that this experience underestimates the degree of risk that might occur with higher doses of thioridazine. Moreover, the effect of fluvoxamine may be even more pronounced when it is administered at higher doses. Therefore, fluvoxamine and thioridazine should not be coadministered [see Contraindications (4.1)]. ","","ncit:positive","ncit:quantitative","3-fold concentration increase","thioridazine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","25","UNK","UNK","Unk","BID","Oral","7","10","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:08:54 -0500","DDI-clinical-trial","evidence-supports","erythrohydrobupropion decreased by 48%. ","In a second healthy volunteer study, ritonavir 600 mg twice daily decreased the AUC and Cmax of bupropion by 66% and 62% respectively. The exposure of the hydroxybupropion metabolite was decreased by 78%, the threohydrobupropion decreased by 50%, and the erythrohydrobupropion decreased by 68%. ","","ncit:positive","ncit:quantitative","Exposure decreased 50%","ritonavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","threohydrobupropion","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","BID","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/cc9e1c8c-0e2b-44e2-878b-27057f786be9.html","2015-08-20 13:57:35 -0400","drug-drug-interaction","evidence-supports"," Immune-Modulating Therapies ","Antineoplastic, immune-modulating, or immunosuppressive therapies, (including corticosteroids) are expected to increase the risk of immunosuppression, and the risk of additive immune system effects must be considered if these therapies are coadministered with GILENYA. When switching from drugs with prolonged immune effects, such as natalizumab, teriflunomide or mitoxantrone, the duration and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects when initiating GILENYA [see Warnings and Precautions (5.2)].","","ncit:positive","ncit:Qualitative",,"GILENYA","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","","natalizumab","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/55816042-946d-4bec-9461-bd998628ff45.html","2015-10-14 11:57:06 -0400","drug-drug-interaction","evidence-supports","tantly administered rifampin. ","Rifampin has been reported to substantially decrease the plasma concentrations of the following antiviral drugs: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir. These antiviral drugs must not be co-administered with rifampin. (See CONTRAINDICATIONS.) ","","ncit:positive","ncit:Qualitative",,"Rifampin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","atazanavir","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-10-29 11:30:54 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type IC antiarrhythmics propafenone and flecainide). While all the SSRIs, e.g., fluoxetine, sertraline, paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"sertraline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:40:46 -0400","DDI-clinical-trial","evidence-supports"," fluvoxamine maleate tablets. ","Coadministration of fluvoxamine maleate 100 mg per day with atenolol 100 mg per day (N = 6) did not affect the plasma concentrations of atenolol. Unlike propranolol and metoprolol which undergo hepatic metabolism, atenolol is eliminated primarily by renal excretion. ","","ncit:negative","ncit:quantitative",,"fluvoxamine maleate","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","atenolol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","100","Daily","Oral","Unk","Daily","Oral","Unk","6","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","pharmacokinetics of lithium . ","Lorazepam-There was no pharmacokinetic interaction between a single dose of Savella (50 mg) and lorazepam (1.5 mg). ","","ncit:negative","ncit:quantitative",,"lorazepam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","50","Savella","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","1.5","SD","tablet","1","SD","tablet","1","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","atment switch is recommended. ","Digoxin-There was no pharmacokinetic interaction between Savella (200 mg/day) and digoxin (0.2 mg/day Lanoxicaps) following multiple-dose administration to healthy subjects. ","","ncit:negative","ncit:quantitative",,"digoxin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","Savella","dikbD2R:drug-product","dikbD2R:object-drug-of-interaction","0.2","Daily","tablet","Unk","Daily","tablet","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:13:55 -0400","DDI-clinical-trial","evidence-supports","","Levothyroxine In healthy subjects who had received EMSAM 6 mg per 24 hours for 10 days, single dose administration with levothyroxine (150 mcg) did not alter the pharmacokinetics of either selegiline or levothyroxine [see Drug Interactions (7.4) and (7.5)].","","ncit:negative","ncit:quantitative",,"levothyroxine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","0.15","EMSAM","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","6","SD","Oral","1","Daily","transdermal","10","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","administration with Savella . ","Clomipramine-Switching from clomipramine (75 mg once a day) to milnacipran (100 mg/day) without a washout period did not lead to clinically significant changes in the pharmacokinetics of milnacipran. Because an increase in adverse events (eg, euphoria and postural hypotension) was observed after switching from clomipramine to milnacipran, monitoring of patients during treatment switch is recommended. ","","ncit:negative","ncit:quantitative",,"milnacipran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","75","clomipramine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","Daily","tablet","Unk","Daily","tablet","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a16297df-3158-48db-85e5-5cd506885556.html","2015-09-29 09:27:10 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine, cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"sertraline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/70b079e2-a1f7-4a93-8685-d60a4d7c1280.html","2015-10-14 12:10:56 -0400","DDI-clinical-trial","evidence-supports","ed (See CONTRAINDICATIONS ). ","CYP 2D6 inhibitors: In healthy subjects, co-administration of pimozide 2 mg (single dose) and paroxetine 60 mg resulted in a 151% increase in pimozide AUC and a 62% increase in pimozide Cmax compared to pimozide administered alone. The increase in pimozide AUC and Cmax is related to the CYP 2D6 inhibitory properties of paroxetine. Concomitant use of pimozide and paroxetine or other strong CYP 2D6 inhibitors are contraindicated (see CONTRAINDICATIONS).","","ncit:positive","ncit:quantitative",,"pimozide","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","2","paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","60","SD","Oral","1","UNK","Oral","Unk","Unk","151","Percent","Increase","Unk","UNK","UNK","62","Percent","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:38:24 -0400","drug-drug-interaction","evidence-supports","AUBAGIO on CYP2C8 substrates ","Teriflunomide is an inhibitor of CYP2C8 in vivo. In patients taking AUBAGIO, exposure of drugs metabolized by CYP2C8 (e.g., paclitaxel, pioglitazone, repaglinide, rosiglitazone) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP2C8 as required [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"pioglitazone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c3ca69e6-1ea0-4c2c-abcb-7264b2e79a87.html","2015-10-29 10:29:25 -0400","drug-drug-interaction","evidence-supports","ients receiving maprotiline . ","Because of the pharmacologic similarity of maprotiline hydrochloride to the tricyclic antidepressants, the plasma concentration of maprotiline may be increased when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), as has occurred with tricyclic antidepressants. Adjustment of the dosage of maprotiline hydrochloride may therefore be necessary in such cases.","","ncit:positive","ncit:Qualitative",,"maprotiline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","maprotiline","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","macokinetics of milnacipran . ","Lithium-Multiple doses of Savella (100 mg/day) did not affect the pharmacokinetics of lithium. ","","ncit:negative","ncit:quantitative",,"Savella","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","100","lithium","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","Daily","tablet","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e338e89-3cf2-48eb-b6e2-a06c608c6513.html","2015-08-20 11:10:08 -0400","drug-drug-interaction","evidence-supports","nical Pharmacology (12.3) ] . ","In a dedicated drug interaction trial, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone [see Clinical Pharmacology (12.3)].","","ncit:negative","ncit:Qualitative",,"ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","abiraterone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:20:54 -0400","DDI-clinical-trial","evidence-supports"," Diazepam ","The coadministration of fluvoxamine maleate tablets and diazepam is generally not advisable. Because fluvoxamine reduces the clearance of both diazepam and its active metabolite, N-desmethyldiazepam, there is a strong likelihood of substantial accumulation of both species during chronic coadministration. Evidence supporting the conclusion that it is inadvisable to coadminister fluvoxamine and diazepam is derived from a study in which healthy volunteers taking 150 mg/day of fluvoxamine were administered a single oral dose of 10 mg of diazepam. In these subjects (N = 8), the clearance of diazepam was reduced by 65% and that of N-desmethyldiazepam to a level that was too low to measure over the course of the 2 week long study. It is likely that this experience significantly underestimates the degree of accumulation that might occur with repeated diazepam administration. Moreover, as noted with alprazolam, the effect of fluvoxamine may even be more pronounced when it is administered at higher doses. Accordingly, diazepam and fluvoxamine should not ordinarily be coadministered. ","","ncit:positive","ncit:quantitative",,"alprazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","10","fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","150","SD","Oral","1","Daily","Oral","UNK","8","Unk","UNK","UNK","65","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b8881a81-75d7-43e8-825f-37c352c146dc.html","2015-11-04 14:19:06 -0500","drug-drug-interaction","evidence-supports","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquine hydroxylase) is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small or quite large (8 fold increase in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics, propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"quinidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e17dc299-f52d-414d-ab6e-e809bd6f8acb.html","2015-11-04 14:14:49 -0500","drug-drug-interaction","evidence-supports","(TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","quinidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:17:38 -0500","DDI-clinical-trial","evidence-supports","Drugs Metabolized by CYP2D6 ","In vitro, bupropion and hydroxybupropion are CYP2D6 inhibitors. In a clinical study of 15 male subjects (ages 19 to 35 years) who were extensive metabolizers of CYP2D6, bupropion given as 150 mg twice daily followed by a single dose of 50 mg desipramine increased the Cmax, AUC, and T1/2 of desipramine by an average of approximately 2-, 5-, and 2-fold, respectively. The effect was present for at least 7 days after the last dose of bupropion. Concomitant use of bupropion with other drugs metabolized by CYP2D6 has not been formally studied.","","ncit:positive","ncit:quantitative",,"desipramine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","50","bupropion","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","150","SD","Oral","1","BID","Oral","Unk","15","5","Fold","Increase","Unk","UNK","UNK","2","Fold","Increase","2","Fold","Increase" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 14:27:00 -0400","drug-drug-interaction","evidence-supports",", etc.) should be used with caution because the clearance of these drugs is likely to be reduced by fluvoxamine . ","The clearance of benzodiazepines metabolized by glucuronidation (e.g., lorazepam, oxazepam, temazepam) is unlikely to be affected by fluvoxamine. ","","ncit:negative","ncit:Qualitative",,"temazepam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","metabolism have not been studied. ","A clinically significant fluvoxamine interaction is possible with drugs having a narrow therapeutic ratio such as pimozide, warfarin, theophylline, certain benzodiazepines, omeprazole and phenytoin. If fluvoxamine maleate tablets are to be administered together with a drug that is eliminated via oxidative metabolism and has a narrow therapeutic window, plasma levels and/or pharmacodynamic effects of the latter drug should be monitored closely, at least until steady-state conditions are reached [see Contraindications (4) and Warnings and Precautions (5)]. ","","ncit:positive","ncit:Qualitative",,"pimozide","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-10-28 15:25:57 -0400","DDI-clinical-trial","evidence-supports","y clinical effect. Phenytoin ","When a single oral 30 mg dose of paroxetine was administered at phenytoin steady state (300 mg once daily for 14 days), paroxetine AUC and T½ were reduced (by an average of 50% and 35%, respectively) compared to paroxetine administered alone. In a separate study, when a single oral 300 mg dose of phenytoin was administered at paroxetine steady state (30 mg once daily for 14 days), phenytoin AUC was slightly reduced (12% on average) compared to phenytoin administered alone. Since both drugs exhibit nonlinear pharmacokinetics, the above studies may not address the case where the 2 drugs are both being chronically dosed. No initial dosage adjustments are considered necessary when these drugs are coadministered; any subsequent adjustments should be guided by clinical effect (see ADVERSE REACTIONS: Postmarketing Reports).","","ncit:positive","ncit:quantitative",,"phenytoin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","300","paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","30","SD","Oral","1","Daily","Oral","14","Unk","12","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","7.1 Potential Interactions with Drugs that Inhibit or are Metabolized by Cytochrome P450 Isoenzymes ","Multiple hepatic cytochrome P450 isoenzymes are involved in the oxidative biotransformation of a large number of structurally different drugs and endogenous compounds. The available knowledge concerning the relationship of fluvoxamine and the cytochrome P450 isoenzyme system has been obtained mostly from pharmacokinetic interaction studies conducted in healthy volunteers, but some preliminary in vitro data are also available. Based on a finding of substantial interactions of fluvoxamine with certain of these drugs [see later parts of this section and also Warnings and Precautions (5)] and limited in vitro data for CYP3A4, it appears that fluvoxamine inhibits several cytochrome P450 isoenzymes that are known to be involved in the metabolism of other drugs such as: CYP1A2 (e.g., warfarin, theophylline, propranolol, tizanidine), CYP2C9 (e.g., warfarin), CYP3A4 (e.g., alprazolam), and CYP2C19 (e.g., omeprazole). ","","ncit:positive","ncit:Qualitative",,"theophylline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ea35caf8-c8c8-481a-97a2-25f68cbc240b.html","2015-09-29 09:04:36 -0400","drug-drug-interaction","evidence-supports","e in plasma AUC of the TCA ). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"flecainide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/55816042-946d-4bec-9461-bd998628ff45.html","2015-10-14 11:57:06 -0400","drug-drug-interaction","evidence-supports","tantly administered rifampin. ","Rifampin has been reported to substantially decrease the plasma concentrations of the following antiviral drugs: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir. These antiviral drugs must not be co-administered with rifampin. (See CONTRAINDICATIONS.) ","","ncit:positive","ncit:Qualitative",,"Rifampin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","antiviral drugs","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:30:38 -0500","DDI-clinical-trial","evidence-supports"," 7.12 Theophylline ","Combined administration of racemic citalopram (40 mg/day for 21 days) and the CYP1A2 substrate theophylline (single dose of 300 mg) did not affect the pharmacokinetics of theophylline. The effect of theophylline on the pharmacokinetics of citalopram was not evaluated. ","","ncit:negative","ncit:quantitative",,"citalopram","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","theophylline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","3000","SD","Oral","1","Daily","Oral","21","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b8881a81-75d7-43e8-825f-37c352c146dc.html","2015-11-04 14:21:12 -0500","drug-drug-interaction","evidence-supports","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquine hydroxylase) is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small or quite large (8 fold increase in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics, propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"flecainide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c66a11c1-3093-45ef-b348-3b196c05ba0c.html","2015-10-01 10:31:02 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dosage regimen of a TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"sertraline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e17dc299-f52d-414d-ab6e-e809bd6f8acb.html","2015-11-04 14:14:49 -0500","drug-drug-interaction","evidence-supports","(TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:33:12 -0400","DDI-clinical-trial","evidence-supports"," Phenytoin ","In healthy male patients (n=18), phenytoin (200 mg daily) increased mirtazapine (30 mg daily) clearance about 2-fold, resulting in a decrease in average plasma mirtazapine concentrations of 45%. Mirtazapine did not significantly affect the pharmacokinetics of phenytoin.","","ncit:negative","ncit:quantitative",,"Mirtazapine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","30","phenytoin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","200","Daily","Oral","Unk","Daily","Oral","Unk","18","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/0177d783-773c-41bf-9db9-eb7e5c64474a.html","2015-11-05 10:40:12 -0500","drug-drug-interaction","evidence-supports","Drugs Metabolized by P450 2D6 ","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7-10% of caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of the isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.","","ncit:positive","ncit:Qualitative",,"paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"tricyclic antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-09-10 15:01:13 -0400","drug-drug-interaction","evidence-supports","yclic Antidepressants (TCAs) ","Significantly increased plasma TCA levels have been reported with the coadministration of fluvoxamine maleate and amitriptyline, clomipramine or imipramine. Caution is indicated with the coadministration of fluvoxamine maleate tablets and TCAs; plasma TCA concentrations may need to be monitored, and the dose of TCA may need to be reduced. ","","ncit:positive","ncit:Qualitative",,"amitriptyline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine maleate","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 13:28:11 -0400","DDI-clinical-trial","evidence-supports","","Carbamazepine Carbamazepine is an enzyme inducer and typically causes decreases in drug exposure; however, approximately 2-fold increased systemic exposure of selegiline and its metabolites, L-amphetamine and L-methamphetamine were seen after single application of EMSAM 6 mg per 24 hours in subjects who had received carbamazepine (400 mg per day) for 14 days. Changes in plasma selegiline concentrations were nearly 2-fold and variable across the subject population. Such increases may increase the risk of a hypertensive crisis when carbamazepine is used with EMSAM at any dose [see Contraindications (4), Warnings and Precautions (5.3) and Drug Interaction (7.4)].","","ncit:positive","ncit:quantitative",,"L-amphetamine","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","Unk","carbamazepine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","6","UNK","UNK","Unk","SD","transdermal","1","Unk","2","Fold","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-10-29 11:30:54 -0400","drug-drug-interaction","evidence-supports","renal elimination with aging. ","Certain drugs, particularly the psychostimulants and the phenothiazines, increase plasma levels of concomitantly administered tricyclic antidepressants through competition for the same metabolic enzyme systems.","","ncit:positive","ncit:Qualitative",,"phenothiazines","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction","","tricyclic antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:17:34 -0400","DDI-clinical-trial","evidence-supports","","Risperidone In subjects who had received EMSAM 6 mg per 24 hours for 10 days, co-administration with risperidone (2 mg per day for 7 days), a substrate for CYP2D6, did not affect the pharmacokinetics of selegiline or risperidone [see Drug Interactions (7.4) and (7.5)].","","ncit:negative","ncit:quantitative",,"EMSAM","dikbD2R:drug-product","dikbD2R:object-drug-of-interaction","6","risperidone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","2","Daily","transdermal","10","Daily","Oral","7","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:39:35 -0400","DDI-clinical-trial","evidence-supports"," Digoxin ","Administration of fluvoxamine maleate 100 mg daily for 18 days (N = 8) did not significantly affect the pharmacokinetics of a 1.25 mg single intravenous dose of digoxin. ","","ncit:negative","ncit:quantitative",,"digoxin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","1.25","fluvoxamine maleate","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","SD","IV","1","Daily","Oral","18","8","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-10-29 11:30:54 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type IC antiarrhythmics propafenone and flecainide). While all the SSRIs, e.g., fluoxetine, sertraline, paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:22:34 -0500","DDI-clinical-trial","evidence-supports"," 7.8 Digoxin ","In subjects who had received 21 days of 40 mg/day racemic citalopram, combined administration of citalopram and digoxin (single dose of 1 mg) did not significantly affect the pharmacokinetics of either citalopram or digoxin. ","","ncit:negative","ncit:quantitative",,"digoxin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","1","citalopram","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","40","Daily","Oral","21","SD","Oral","1","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1809bcb4-5fcc-45ca-986a-4fa5edcd4b5e.html","2015-09-29 09:58:27 -0400","drug-drug-interaction","evidence-supports","er tricyclic antidepressants. ","The plasma concentration of CMI has been reported to be increased by the concomitant administration of haloperidol; plasma levels of several closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of methylphenidate or hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by the concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin), and such an effect may be anticipated with CMI as well. Administration of CMI has been reported to increase the plasma levels of phenobarbital, if given concomitantly (see CLINICAL PHARMACOLOGY, Interactions).","","ncit:positive","ncit:Qualitative",,"CMI","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","haloperidol","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:42:22 -0400","drug-drug-interaction","evidence-supports","nical Pharmacology (12.3) ] . ","No dose adjustment for EMSAM is needed when EMSAM is used concomitantly with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and CYP3A4 inhibitors (e.g., ketoconazole). No clinically meaningful change in selegiline exposure was seen when EMSAM was co-administered with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and ketoconazole [see Clinical Pharmacology (12.3)]. ","","ncit:negative","ncit:Qualitative",,"olanzapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","EMSAM","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:42:22 -0400","drug-drug-interaction","evidence-supports","nical Pharmacology (12.3) ] . ","No dose adjustment of alprazolam, ibuprofen, levothyroxine, olanzapine, risperdione, warfarin, or strong CYP3A4 inhibitors (e.g., ketoconazole) is necessary when these drugs are used in combination with EMSAM. EMSAM had no clinically relevant effect on pharmacokinetics of these drugs.","","ncit:negative","ncit:Qualitative",,"EMSAM","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","","ibuprofen","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:16:45 -0400","DDI-clinical-trial","evidence-supports","","Pseudoephedrine EMSAM 6 mg per 24 hours for 10 days, co-administered with pseudoephedrine (60 mg, 3 times a day) did not affect the pharmacokinetics of pseudoephedrine. There were no clinically significant changes in blood pressure during pseudoephedrine administration alone, or in combination with EMSAM [see Drug Interactions (7.4) and (7.5)]. ","","ncit:negative","ncit:quantitative",,"pseudoephedrine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","60","EMSAM","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","6","TID","Oral","Unk","Daily","transdermal","10","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:38:24 -0400","drug-drug-interaction","evidence-supports","BAGIO on oral contraceptives ","AUBAGIO may increase the systemic exposures of ethinylestradiol and levonorgestrel. Consideration should be given to the type or dose of contraceptives used in combination with AUBAGIO [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"levonorgestrel","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","AUBAGIO","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-10-29 11:30:54 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type IC antiarrhythmics propafenone and flecainide). While all the SSRIs, e.g., fluoxetine, sertraline, paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction",,"cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","7.1 Potential Interactions with Drugs that Inhibit or are Metabolized by Cytochrome P450 Isoenzymes ","Multiple hepatic cytochrome P450 isoenzymes are involved in the oxidative biotransformation of a large number of structurally different drugs and endogenous compounds. The available knowledge concerning the relationship of fluvoxamine and the cytochrome P450 isoenzyme system has been obtained mostly from pharmacokinetic interaction studies conducted in healthy volunteers, but some preliminary in vitro data are also available. Based on a finding of substantial interactions of fluvoxamine with certain of these drugs [see later parts of this section and also Warnings and Precautions (5)] and limited in vitro data for CYP3A4, it appears that fluvoxamine inhibits several cytochrome P450 isoenzymes that are known to be involved in the metabolism of other drugs such as: CYP1A2 (e.g., warfarin, theophylline, propranolol, tizanidine), CYP2C9 (e.g., warfarin), CYP3A4 (e.g., alprazolam), and CYP2C19 (e.g., omeprazole). ","","ncit:positive","ncit:Qualitative",,"fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"alprazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:56:02 -0500","DDI-clinical-trial","evidence-supports","may be necessary when coadministered with nefazodone . ","Lorazepam – When lorazepam (2 mg BID) and nefazodone (200 mg BID) were coadministered to steady state, there was no change in any pharmacokinetic parameter for either drug compared to each drug administered alone. Therefore, dosage adjustment is not necessary for either drug when coadministered.","","ncit:negative","ncit:quantitative",,"nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","lorazepam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","2","BID","Oral","Unk","BID","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:48:50 -0400","drug-drug-interaction","evidence-supports","nsporter 3 (OAT3) substrates ","Teriflunomide inhibits the activity of OAT3 in vivo. In patients taking AUBAGIO, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) which are OAT3 substrates as required [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"ketoprofen","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:33:30 -0500","DDI-clinical-trial","evidence-supports"," 7.16 Ketoconazole ","Combined administration of racemic citalopram (40 mg) and ketoconazole (200 mg), a potent CYP3A4 inhibitor, decreased the Cmax and AUC of ketoconazole by 21% and 10%, respectively, and did not significantly affect the pharmacokinetics of citalopram. ","","ncit:positive","ncit:quantitative",,"citalopram","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","ketoconazole","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","200","UNK","Oral","Unk","UNK","Oral","Unk","Unk","21","Percent","Decrease","Unk","UNK","UNK","10","Percent","Decrease","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 12:50:04 -0400","drug-drug-interaction","evidence-supports"," B3 (OATP1B1/1B3) substrates ","Teriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo. For a patient taking AUBAGIO, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking AUBAGIO [see Clinical Pharmacology (12.3)]","","ncit:positive","ncit:Qualitative",,"methotrexate","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b8881a81-75d7-43e8-825f-37c352c146dc.html","2015-11-04 14:19:06 -0500","drug-drug-interaction","evidence-supports","Hyperpyrexia has been reported when tricyclic antidepressants are administered with anticholinergic agents or with neuroleptic drugs, particularly during hot weather. ","Cimetidine is reported to reduce hepatic metabolism of certain tricyclic antidepressants, thereby delaying elimination and increasing steady-state concentrations of these drugs. Clinically significant effects have been reported with the tricyclic antidepressants when used concomitantly with cimetidine. Increases in plasma levels of tricyclic antidepressants, and in the frequency and severity of side-effects, particularly anticholinergic, have been reported when cimetidine was added to the drug regimen. Discontinuation of cimetidine in well-controlled patients receiving tricyclic antidepressants and cimetidine may decrease the plasma levels and efficacy of the antidepressants.","","ncit:positive","ncit:Qualitative",,"Cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"tricyclic antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:31:16 -0400","DDI-clinical-trial","evidence-supports"," Theophylline ","The effect of steady-state fluvoxamine (50 mg bid) on the pharmacokinetics of a single dose of theophylline (375 mg as 442 mg aminophylline) was evaluated in 12 healthy non-smoking, male volunteers. The clearance of theophylline was decreased approximately 3-fold. Therefore, if theophylline is coadministered with fluvoxamine maleate, its dose should be reduced to one-third of the usual daily maintenance dose and plasma concentrations of theophylline should be monitored. No dosage adjustment is required for fluvoxamine maleate tablets.","","ncit:positive","ncit:quantitative",,"fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","50","theophylline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","375","SD","Oral","1","BID","Oral","Unk","12","Unk","UNK","UNK","3","Fold","Decrease","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:38:24 -0400","drug-drug-interaction","evidence-supports","AUBAGIO on CYP2C8 substrates ","Teriflunomide is an inhibitor of CYP2C8 in vivo. In patients taking AUBAGIO, exposure of drugs metabolized by CYP2C8 (e.g., paclitaxel, pioglitazone, repaglinide, rosiglitazone) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP2C8 as required [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","repaglinide","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:13:01 -0400","DDI-clinical-trial","evidence-supports","","Carbamazepine Carbamazepine is an enzyme inducer and typically causes decreases in drug exposure; however, approximately 2-fold increased systemic exposure of selegiline and its metabolites, L-amphetamine and L-methamphetamine were seen after single application of EMSAM 6 mg per 24 hours in subjects who had received carbamazepine (400 mg per day) for 14 days. Changes in plasma selegiline concentrations were nearly 2-fold and variable across the subject population. Such increases may increase the risk of a hypertensive crisis when carbamazepine is used with EMSAM at any dose [see Contraindications (4), Warnings and Precautions (5.3) and Drug Interaction (7.4)].","","ncit:positive","ncit:quantitative",,"carbamazepine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","400","selegiline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","6","SD","transdermal","1","Daily","Oral","14","Unk","2","Fold","Increase","Unk","UNK","UNK","2","Fold","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:24:24 -0500","drug-drug-interaction","evidence-supports","XL and drugs that are inhibitors or inducers of CYP2B6. Inhibitors of CYP2B6 ","Ticlopidine and Clopidogrel: Concomitant treatment with these drugs can increase bupropion exposures but decrease hydroxybupropion exposure. Based on clinical response, dosage adjustment of WELLBUTRIN XL may be necessary when coadministered with CYP2B6 inhibitors (e.g., ticlopidine or clopidogrel) [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"Ticlopidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"hydroxybupropion","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","metabolism have not been studied. ","A clinically significant fluvoxamine interaction is possible with drugs having a narrow therapeutic ratio such as pimozide, warfarin, theophylline, certain benzodiazepines, omeprazole and phenytoin. If fluvoxamine maleate tablets are to be administered together with a drug that is eliminated via oxidative metabolism and has a narrow therapeutic window, plasma levels and/or pharmacodynamic effects of the latter drug should be monitored closely, at least until steady-state conditions are reached [see Contraindications (4) and Warnings and Precautions (5)]. ","","ncit:positive","ncit:Qualitative",,"omeprazole","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/829a4f51-c882-4b64-81f3-abfb03a52ebe.html","2015-10-29 09:04:44 -0400","DDI-clinical-trial","evidence-supports"," 7.6 Temazepam ","Under steady-state conditions for duloxetine (20 mg qhs) and temazepam (30 mg qhs), the pharmacokinetics of duloxetine were not affected by co-administration. ","","ncit:negative","ncit:quantitative",,"duloxetine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","20","temazepam","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","30","UNK","Oral","Unk","UNK","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:56:02 -0500","DDI-clinical-trial","evidence-supports","Monoamine Oxidase Inhibitors – See WARNINGS . ","Haloperidol – When a single oral 5 mg dose of haloperidol was coadministered with nefazodone (200 mg BID) at steady state, haloperidol apparent clearance decreased by 35% with no significant increase in peak haloperidol plasma concentrations or time of peak. This change is of unknown clinical significance. Pharmacodynamic effects of haloperidol were generally not altered significantly. There were no changes in the pharmacokinetic parameters for nefazodone. Dosage adjustment of haloperidol may be necessary when coadministered with nefazodone.","","ncit:positive","ncit:quantitative",,"haloperidol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","5","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","SD","Oral","1","BID","Oral","Unk","Unk","Unk","UNK","UNK","35","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-09-10 15:01:13 -0400","drug-drug-interaction","evidence-supports","yclic Antidepressants (TCAs) ","Significantly increased plasma TCA levels have been reported with the coadministration of fluvoxamine maleate and amitriptyline, clomipramine or imipramine. Caution is indicated with the coadministration of fluvoxamine maleate tablets and TCAs; plasma TCA concentrations may need to be monitored, and the dose of TCA may need to be reduced. ","","ncit:positive","ncit:Qualitative",,"fluvoxamine maleate","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","clomipramine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:38:52 -0400","DDI-clinical-trial","evidence-supports"," Ketoconazole ","In healthy, male, Caucasian patients (n=24), coadministration of the potent CYP3A4 inhibitor ketoconazole (200 mg b.i.d. for 6.5 days) increased the peak plasma levels and the AUC of a single 30-mg dose of mirtazapine by approximately 40% and 50%, respectively. Caution should be exercised when coadministering mirtazapine with potent CYP3A4 inhibitors, HIV protease inhibitors, azole antifungals, erythromycin, or nefazodone.","","ncit:positive","ncit:quantitative",,"mirtazapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","30","ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","SD","Oral","1","BID","Oral","6.5","24","50","Percent","Increase","Unk","UNK","UNK","40","Percent","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/829a4f51-c882-4b64-81f3-abfb03a52ebe.html","2015-10-29 09:00:42 -0400","DDI-clinical-trial","evidence-supports","ibition of CYP1A2 and CYP2D6 ","Concomitant administration of duloxetine 40 mg twice daily with fluvoxamine 100 mg, a potent CYP1A2 inhibitor, to CYP2D6 poor metabolizer subjects (n=14) resulted in a 6-fold increase in duloxetine AUC and Cmax.","","ncit:positive","ncit:quantitative",,"duloxetine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","40","fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","BID","Oral","Unk","UNK","Oral","Unk","Unk","6","Fold","Increase","Unk","UNK","UNK","6","Fold","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 14:01:03 -0500","DDI-clinical-trial","evidence-supports","","Imipramine and Other Tricyclic Antidepressants (TCAs) - In vitro studies suggest that citalopram is a relatively weak inhibitor of CYP2D6. Coadministration of Celexa (40 mg/day for 10 days) with the TCA imipramine (single dose of 100 mg), a substrate for CYP2D6, did not significantly affect the plasma concentrations of imipramine or citalopram. However, the concentration of the imipramine metabolite desipramine was increased by approximately 50%. The clinical significance of the desipramine change is unknown. Nevertheless, caution is indicated in the coadministration of TCAs with Celexa.","","ncit:negative","ncit:quantitative",,"citalopram","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","imipramine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","100","SD","Oral","1","Daily","Oral","10","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/cc9e1c8c-0e2b-44e2-878b-27057f786be9.html","2015-08-20 13:57:35 -0400","drug-drug-interaction","evidence-supports","beta blockers or diltiazem ) ","Experience with GILENYA in patients receiving concurrent therapy with drugs that slow the heart rate or atrioventricular conduction (e.g., beta blockers, digoxin, or heart rate-slowing calcium channel blockers such as diltiazem or verapamil) is limited. Because initiation of GILENYA treatment may result in an additional decrease in heart rate, concomitant use of these drugs during GILENYA initiation may be associated with severe bradycardia or heart block. Seek advice from the prescribing physician regarding the possibility to switch to drugs that do not slow the heart rate or atrioventricular conduction before initiating GILENYA. Patients who cannot switch, should have overnight continuous ECG monitoring after the first dose [see Dosage and Administration (2) and Warnings and Precautions (5.1)]","","ncit:positive","ncit:Qualitative",,"GILENYA","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","","calcium channel blockers","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-09-14 11:03:10 -0400","DDI-clinical-trial","evidence-supports","y clinical effect. Phenytoin ","When a single oral 30 mg dose of paroxetine was administered at phenytoin steady state (300 mg once daily for 14 days), paroxetine AUC and T½ were reduced (by an average of 50% and 35%, respectively) compared to paroxetine administered alone. In a separate study, when a single oral 300 mg dose of phenytoin was administered at paroxetine steady state (30 mg once daily for 14 days), phenytoin AUC was slightly reduced (12% on average) compared to phenytoin administered alone. Since both drugs exhibit nonlinear pharmacokinetics, the above studies may not address the case where the 2 drugs are both being chronically dosed. No initial dosage adjustments are considered necessary when these drugs are coadministered; any subsequent adjustments should be guided by clinical effect (see ADVERSE REACTIONS: Postmarketing Reports).","","ncit:positive","ncit:quantitative",,"phenytoin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","300","paroxetine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","30","SD","Oral","1","Daily","Oral","14","Unk","50","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK","35","Percent","Decrease" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","DDI-clinical-trial","evidence-supports","2 in vivo . OAT3 Substrates ","There was an increase in mean cefaclor Cmax and AUC (1.43- and 1.54-fold, respectively), following repeated doses of teriflunomide, suggesting that teriflunomide is an inhibitor of organic anion transporter 3 (OAT3) in vivo [see Drug Interactions (7)].","","ncit:positive","ncit:quantitative",,"teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","cefaclor","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","1.54","Fold","Increase","Unk","UNK","UNK","1.43","Fold","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-09-29 11:28:40 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type IC antiarrhythmics propafenone and flecainide). While all the SSRIs, e.g., fluoxetine, sertraline, paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","phenothiazines","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:15:20 -0400","DDI-clinical-trial","evidence-supports","","Olanzapine In subjects who had received EMSAM 6 mg per 24 hours for 10 days, co-administration with olanzapine, a substrate for CYP1A2, CYP2D6, and possibly CYP2A6, did not affect the pharmacokinetics of selegiline or olanzapine [see Drug Interactions (7.4) and (7.5)].","","ncit:negative","ncit:quantitative",,"olanzapine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","EMSAM","dikbD2R:drug-product","dikbD2R:object-drug-of-interaction","6","Daily","transdermal","10","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 14:00:45 -0500","DDI-clinical-trial","evidence-supports","","Imipramine and Other Tricyclic Antidepressants (TCAs) - In vitro studies suggest that citalopram is a relatively weak inhibitor of CYP2D6. Coadministration of Celexa (40 mg/day for 10 days) with the TCA imipramine (single dose of 100 mg), a substrate for CYP2D6, did not significantly affect the plasma concentrations of imipramine or citalopram. However, the concentration of the imipramine metabolite desipramine was increased by approximately 50%. The clinical significance of the desipramine change is unknown. Nevertheless, caution is indicated in the coadministration of TCAs with Celexa.","","ncit:positive","ncit:quantitative",,"desipramine","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","Unk","citalopram","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","UNK","UNK","Unk","Daily","Oral","10","Unk","Unk","UNK","UNK","Unk","UNK","UNK","50","Percent","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 13:28:11 -0400","DDI-clinical-trial","evidence-supports","","Alprazolam In subjects who had received EMSAM 6 mg per 24 hours for 7 days, co-administration with alprazolam (15 mg per day), a CYP3A4 and CYP3A5 substrate, did not affect the pharmacokinetics of alprazolam or selegiline [see Drug Interactions (7.4) and (7.5)]. ","","ncit:negative","ncit:quantitative",,"EMSAM","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","6","alprazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","15","Daily","Oral","7","Daily","transdermal","7","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a9ff32c4-3bcf-4e51-ae8c-81ff0191ec35.html","2015-10-28 17:20:54 -0400","DDI-clinical-trial","evidence-supports",", metoprolol , atomoxetine ) ","In vitro studies showed minimal inhibitory effect of desvenlafaxine on CYP2D6. Clinical studies have shown that desvenlafaxine does not have a clinically relevant effect on CYP2D6 metabolism at the dose of 100 mg daily. When desvenlafaxine succinate was administered at a dose of 100 mg daily in conjunction with a single 50 mg dose of desipramine, a CYP2D6 substrate, the Cmax and AUC of desipramine increased approximately 25% and 17%, respectively. When 400 mg (8 times the recommended 50 mg dose) was administered, the Cmax and AUC of desipramine increased approximately 50% and 90%, respectively. Concomitant use of desvenlafaxine with a drug metabolized by CYP2D6 can result in higher concentrations of that drug [see Drug Interactions (7.5)].","","ncit:positive","ncit:quantitative",,"desipramine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","500","desvenlafaxine succinate","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","SD","Oral","1","Daily","Oral","Unk","Unk","17","Percent","Increase","Unk","UNK","UNK","25","Percent","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:25:55 -0500","drug-drug-interaction","evidence-supports","Clinical Pharmacology (12.3) ]. Inducers of CYP2B6 ","Ritonavir, Lopinavir, and Efavirenz: Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure. Dosage increase of WELLBUTRIN XL may be necessary when coadministered with ritonavir, lopinavir, or efavirenz but should not exceed the maximum recommended dose [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"bupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Efavirenz","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b8881a81-75d7-43e8-825f-37c352c146dc.html","2015-11-04 14:21:12 -0500","drug-drug-interaction","evidence-supports","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquine hydroxylase) is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small or quite large (8 fold increase in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics, propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","phenothiazines","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/f371258d-91b3-4b6a-ac99-434a1964c3af.html","2015-10-29 09:45:11 -0400","drug-drug-interaction","evidence-supports","is not an inhibitor of CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, P-gp, OATP1B1, OATP1B3, OAT1, OAT3, or OCT2. ","Concomitant use of FETZIMA with alprazolam or carbamazepine, substrates of CYP3A4, had no significant effect on alprazolam or carbamazepine plasma concentrations ","","ncit:negative","ncit:Qualitative",,"carbamazepine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","FETZIMA","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c3ca69e6-1ea0-4c2c-abcb-7264b2e79a87.html","2015-09-30 12:41:52 -0400","drug-drug-interaction","evidence-supports","ients receiving maprotiline . ","Because of the pharmacologic similarity of maprotiline hydrochloride to the tricyclic antidepressants, the plasma concentration of maprotiline may be increased when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), as has occurred with tricyclic antidepressants. Adjustment of the dosage of maprotiline hydrochloride may therefore be necessary in such cases.","","ncit:positive","ncit:Qualitative",,"maprotiline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:07:34 -0500","DDI-clinical-trial","evidence-supports","erythrohydrobupropion decreased by 48%. ","In a second healthy volunteer study, ritonavir 600 mg twice daily decreased the AUC and Cmax of bupropion by 66% and 62% respectively. The exposure of the hydroxybupropion metabolite was decreased by 78%, the threohydrobupropion decreased by 50%, and the erythrohydrobupropion decreased by 68%. ","","ncit:positive","ncit:quantitative",,"bupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","ritonavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","UNK","UNK","Unk","BID","Oral","Unk","Unk","66","Percent","Decrease","Unk","UNK","UNK","62","Percent","Decrease","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:35:24 -0400","DDI-clinical-trial","evidence-supports"," Cimetidine ","In healthy male patients (n=12), when cimetidine, a weak inhibitor of CYP1A2, CYP2D6, and CYP3A4, given at 800 mg b.i.d. at steady state was coadministered with mirtazapine (30 mg daily) at steady state, the Area Under the Curve (AUC) of mirtazapine increased more than 50%. Mirtazapine did not cause relevant changes in the pharmacokinetics of cimetidine. The mirtazapine dose may have to be decreased when concomitant treatment with cimetidine is started, or increased when cimetidine treatment is discontinued.","","ncit:negative","ncit:quantitative",,"cimetidine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","800","Mirtazapine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","30","BID","Oral","Unk","Daily","Oral","Unk","12","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","drug-drug-interaction","evidence-supports","ct of Other Drugs on AUBAGIO ","Potent CYP and transporter inducers: Rifampin did not affect the pharmacokinetics of teriflunomide.","","ncit:negative","ncit:Qualitative",,"teriflunomide","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Rifampin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f356c1b-96bd-4ef1-960c-91cf4905e6b1.html","2015-09-10 14:36:47 -0400","drug-drug-interaction","evidence-supports","","Anticonvulsants — Patients on stable doses of phenytoin and carbamazepine have developed elevated plasma anticonvulsant concentrations and clinical anticonvulsant toxicity following initiation of concomitant fluoxetine treatment. ","","ncit:positive","ncit:Qualitative",,"phenytoin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/7c295b64-ec39-42ec-9f02-da5b42e775e1.html","2015-08-20 10:29:59 -0400","drug-drug-interaction","evidence-supports","","Clinical studies have not shown any drug interactions between bicalutamide and LHRH analogs (goserelin or leuprolide). There is no evidence that bicalutamide induces hepatic enzymes.","","ncit:negative","ncit:Qualitative",,"goserelin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","bicalutamide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1809bcb4-5fcc-45ca-986a-4fa5edcd4b5e.html","2015-10-29 11:26:06 -0400","drug-drug-interaction","evidence-supports","plasma concentrations of CMI . ","Co-administration of CMI with phenobarbital increases plasma concentrations of phenobarbital ","","ncit:positive","ncit:Qualitative",,"CMI","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"phenobarbital","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:43:14 -0500","drug-drug-interaction","evidence-supports","Potential Terfenadine, Astemizole, Cisapride, and Pimozide Interactions ","Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. Increased plasma concentrations of terfenadine, astemizole, cisapride, and pimozide are associated with QT prolongation and with rare cases of serious cardiovascular adverse events, including death, due principally to ventricular tachycardia of the torsade de pointes type. Nefazodone has been shown in vitro to be an inhibitor of CYP3A4. Consequently, it is recommended that nefazodone not be used in combination with either terfenadine, astemizole, cisapride, or pimozide (see CONTRAINDICATIONS and PRECAUTIONS).","","ncit:positive","ncit:Qualitative",,"nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"astemizole","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c00d1607-ac36-457b-a34b-75ad74f9cf0a.html","2015-10-13 11:13:09 -0400","drug-drug-interaction","evidence-supports","ther Drugs to Affect INVIRASE ","The metabolism of saquinavir is mediated primarily by CYP3A. Additionally, saquinavir is a substrate for P-glycoprotein (P-gp). Therefore, drugs that affect CYP3A and/or P-gp may modify the pharmacokinetics of saquinavir. Coadministration with drugs that are potent inducers of CYP3A (e.g., phenobarbital, phenytoin, carbamazepine) may result in decreased plasma concentrations of saquinavir and reduced therapeutic effect.","","ncit:positive","ncit:Qualitative",,"saquinavir","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","carbamazepine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c66a11c1-3093-45ef-b348-3b196c05ba0c.html","2015-10-29 11:36:34 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dosage regimen of a TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"propafenone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 11:47:01 -0400","drug-drug-interaction","evidence-supports","Clinical Pharmacology (12.3) ] . ","No dose adjustment of alprazolam, ibuprofen, levothyroxine, olanzapine, risperdione, warfarin, or strong CYP3A4 inhibitors (e.g., ketoconazole) is necessary when these drugs are used in combination with EMSAM. EMSAM had no clinically relevant effect on pharmacokinetics of these drugs.","","ncit:negative","ncit:Qualitative",,"ketoconazole","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","EMSAM","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e338e89-3cf2-48eb-b6e2-a06c608c6513.html","2015-08-20 11:30:25 -0400","DDI-clinical-trial","evidence-supports","of theophylline was observed. ","Abiraterone is a substrate of CYP3A4, in vitro. In a clinical pharmacokinetic interaction study of healthy subjects pretreated with a strong CYP3A4 inducer (rifampin, 600 mg daily for 6 days) followed by a single dose of abiraterone acetate 1,000 mg, the mean plasma AUC∞ of abiraterone was decreased by 55% [see Drug Interactions (7.1)].","","ncit:positive","ncit:quantitative",,"abiraterone acetate","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","600","rifampin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","1000","SD","UNK","1","Daily","UNK","6","Unk","55","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:56:21 -0500","DDI-clinical-trial","evidence-supports","","Triazolam - Combined administration of Celexa (titrated to 40 mg/day for 28 days) and the CYP3A4 substrate triazolam (single dose of 0.25 mg) did not significantly affect the pharmacokinetics of either citalopram or triazolam.","","ncit:negative","ncit:quantitative",,"Celexa","dikbD2R:drug-product","dikbD2R:object-drug-of-interaction","40","triazolam","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","0.25","Daily","Oral","28","SD","Oral","1","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:29:30 -0400","drug-drug-interaction","evidence-supports"," Clozapine ","Elevated serum levels of clozapine have been reported in patients taking fluvoxamine maleate and clozapine. Since clozapine-related seizures and orthostatic hypotension appear to be dose related, the risk of these adverse events may be higher when fluvoxamine and clozapine are coadministered. Patients should be closely monitored when fluvoxamine maleate and clozapine are used concurrently. ","","ncit:positive","ncit:Qualitative",,"clozapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine maleate","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 12:50:04 -0400","drug-drug-interaction","evidence-supports"," B3 (OATP1B1/1B3) substrates ","Teriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo. For a patient taking AUBAGIO, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking AUBAGIO [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"nateglinide","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/cc9e1c8c-0e2b-44e2-878b-27057f786be9.html","2015-08-20 13:57:35 -0400","drug-drug-interaction","evidence-supports"," Immune-Modulating Therapies ","Antineoplastic, immune-modulating, or immunosuppressive therapies, (including corticosteroids) are expected to increase the risk of immunosuppression, and the risk of additive immune system effects must be considered if these therapies are coadministered with GILENYA. When switching from drugs with prolonged immune effects, such as natalizumab, teriflunomide or mitoxantrone, the duration and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects when initiating GILENYA [see Warnings and Precautions (5.2)].","","ncit:positive","ncit:Qualitative",,"GILENYA","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","","teriflunomide","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:46:43 -0400","DDI-clinical-trial","evidence-supports","450 2D6 under PRECAUTIONS ). ","Hypoglycemic Drugs–In a placebo-controlled trial in normal volunteers, administration of sertraline for 22 days (including 200 mg/day for the final 13 days) caused a statistically significant 16% decrease from baseline in the clearance of tolbutamide following an intravenous 1000 mg dose. Sertraline administration did not noticeably change either the plasma protein binding or the apparent volume of distribution of tolbutamide, suggesting that the decreased clearance was due to a change in the metabolism of the drug. The clinical significance of this decrease in tolbutamide clearance is unknown.","","ncit:positive","ncit:quantitative",,"tolbutamide","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","1000","sertraline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","SD","IV","1","Daily","Oral","22","Unk","Unk","UNK","UNK","16","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a16297df-3158-48db-85e5-5cd506885556.html","2015-09-29 09:27:10 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine, cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"propafenone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ea35caf8-c8c8-481a-97a2-25f68cbc240b.html","2015-09-29 09:04:36 -0400","drug-drug-interaction","evidence-supports","e in plasma AUC of the TCA ). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:48:13 -0500","DDI-clinical-trial","evidence-supports","olized by Cytochrome P4502D6 ","In vitro studies did not reveal an inhibitory effect of escitalopram on CYP2D6. In addition, steady state levels of racemic citalopram were not significantly different in poor metabolizers and extensive CYP2D6 metabolizers after multiple-dose administration of citalopram, suggesting that coadministration, with escitalopram, of a drug that inhibits CYP2D6, is unlikely to have clinically significant effects on escitalopram metabolism. However, there are limited in vivo data suggesting a modest CYP2D6 inhibitory effect for escitalopram, i.e., coadministration of escitalopram (20 mg/day for 21 days) with the tricyclic antidepressant desipramine (single dose of 50 mg), a substrate for CYP2D6, resulted in a 40% increase in Cmax and a 100% increase in AUC of desipramine. The clinical significance of this finding is unknown. Nevertheless, caution is indicated in the coadministration of escitalopram and drugs metabolized by CYP2D6. ","","ncit:positive","ncit:quantitative",,"desipramine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","50","escitalopram","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","SD","Oral","1","Daily","Oral","21","Unk","100","Percent","Increase","Unk","UNK","UNK","40","Percent","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-09-14 11:21:10 -0400","DDI-clinical-trial","evidence-supports","stered with lithium. Digoxin ","The steady-state pharmacokinetics of paroxetine was not altered when administered with digoxin at steady state. Mean digoxin AUC at steady state decreased by 15% in the presence of paroxetine. Since there is little clinical experience, the concurrent administration of paroxetine and digoxin should be undertaken with caution.","","ncit:positive","ncit:quantitative",,"paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","digoxin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","15","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:13:01 -0400","DDI-clinical-trial","evidence-supports","","Ketoconazole Seven-day treatment with ketoconazole (200 mg per day), a potent inhibitor of CYP3A4, did not affect the steady-state pharmacokinetics of selegiline in subjects who received EMSAM 6 mg per 24 hours for 7 days and no differences in the pharmacokinetics of ketoconazole were observed [see Drug Interactions (7.4) and (7.5)]. ","","ncit:negative","ncit:quantitative",,"ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","selegiline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","6","Daily","transdermal","7","Daily","Oral","7","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c3ca69e6-1ea0-4c2c-abcb-7264b2e79a87.html","2015-10-29 10:29:25 -0400","drug-drug-interaction","evidence-supports","ients receiving maprotiline . ","Because of the pharmacologic similarity of maprotiline hydrochloride to the tricyclic antidepressants, the plasma concentration of maprotiline may be increased when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), as has occurred with tricyclic antidepressants. Adjustment of the dosage of maprotiline hydrochloride may therefore be necessary in such cases.","","ncit:positive","ncit:Qualitative",,"phenytoin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","maprotiline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 13:28:11 -0400","DDI-clinical-trial","evidence-supports","","Alprazolam In subjects who had received EMSAM 6 mg per 24 hours for 7 days, co-administration with alprazolam (15 mg per day), a CYP3A4 and CYP3A5 substrate, did not affect the pharmacokinetics of alprazolam or selegiline [see Drug Interactions (7.4) and (7.5)]. ","","ncit:negative","ncit:quantitative",,"alprazolam","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","15","EMSAM","dikbD2R:drug-product","dikbD2R:object-drug-of-interaction","6","Daily","transdermal","7","Daily","Oral","7","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:42:22 -0400","drug-drug-interaction","evidence-supports","nical Pharmacology (12.3) ] . ","No dose adjustment of alprazolam, ibuprofen, levothyroxine, olanzapine, risperdione, warfarin, or strong CYP3A4 inhibitors (e.g., ketoconazole) is necessary when these drugs are used in combination with EMSAM. EMSAM had no clinically relevant effect on pharmacokinetics of these drugs.","","ncit:negative","ncit:Qualitative",,"EMSAM","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","","warfarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 12:50:04 -0400","drug-drug-interaction","evidence-supports"," B3 (OATP1B1/1B3) substrates ","Teriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo. For a patient taking AUBAGIO, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking AUBAGIO [see Clinical Pharmacology (12.3)]","","ncit:positive","ncit:Qualitative",,"repaglinide","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:43:14 -0500","drug-drug-interaction","evidence-supports","Potential Terfenadine, Astemizole, Cisapride, and Pimozide Interactions ","Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. Increased plasma concentrations of terfenadine, astemizole, cisapride, and pimozide are associated with QT prolongation and with rare cases of serious cardiovascular adverse events, including death, due principally to ventricular tachycardia of the torsade de pointes type. Nefazodone has been shown in vitro to be an inhibitor of CYP3A4. Consequently, it is recommended that nefazodone not be used in combination with either terfenadine, astemizole, cisapride, or pimozide (see CONTRAINDICATIONS and PRECAUTIONS).","","ncit:positive","ncit:Qualitative",,"cisapride","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:24:24 -0500","drug-drug-interaction","evidence-supports","XL and drugs that are inhibitors or inducers of CYP2B6. Inhibitors of CYP2B6 ","Ticlopidine and Clopidogrel: Concomitant treatment with these drugs can increase bupropion exposures but decrease hydroxybupropion exposure. Based on clinical response, dosage adjustment of WELLBUTRIN XL may be necessary when coadministered with CYP2B6 inhibitors (e.g., ticlopidine or clopidogrel) [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"bupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Clopidogrel","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c3ca69e6-1ea0-4c2c-abcb-7264b2e79a87.html","2015-10-29 10:29:25 -0400","drug-drug-interaction","evidence-supports","is rapidly tapered in patients receiving maprotiline . ","Because of the pharmacologic similarity of maprotiline hydrochloride to the tricyclic antidepressants, the plasma concentration of maprotiline may be increased when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), as has occurred with tricyclic antidepressants. Adjustment of the dosage of maprotiline hydrochloride may therefore be necessary in such cases.","","ncit:positive","ncit:Qualitative",,"barbiturates","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","","maprotiline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/0177d783-773c-41bf-9db9-eb7e5c64474a.html","2015-11-05 10:40:12 -0500","drug-drug-interaction","evidence-supports","Drug Interactions Cimetidine ","There is evidence that cimetidine inhibits the elimination of tricyclic antidepressants. Downward adjustment of SURMONTIL dosage may be required if cimetidine therapy is initiated; upward adjustment if cimetidine therapy is discontinued.","","ncit:positive","ncit:Qualitative",,"cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"SURMONTIL","dikbD2R:drug-product","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:43:54 -0400","drug-drug-interaction","evidence-supports","AUBAGIO on CYP1A2 substrates ","Teriflunomide may be a weak inducer of CYP1A2 in vivo. In patients taking AUBAGIO, exposure of drugs metabolized by CYP1A2 (e.g., alosetron, duloxetine, theophylline, tizanidine) may be reduced. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP1A2 as required [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","alosetron","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/f371258d-91b3-4b6a-ac99-434a1964c3af.html","2015-10-29 09:45:11 -0400","DDI-clinical-trial","evidence-supports","ketoconazole (see Figure 1 ). ","No dose adjustment of FETZIMA is needed when co-administered with a CYP3A4 inducer or substrate. In vivo studies showed no clinically meaningful change in levomilnacipran exposure when co-administered with the CYP3A4 inducer carbamazepine or the CYP3A4 substrate alprazolam (see Figure 1). ","","ncit:negative","ncit:quantitative",,"levomilnacipran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","alprazolam","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","phenothiazines","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:36:27 -0400","DDI-clinical-trial","evidence-supports","dDOSAGE AND ADMINISTRATION . ","Drugs Metabolized by P450 3A4–In three separate in vivo interaction studies, sertraline was co-administered with cytochrome P450 3A4 substrates, terfenadine, carbamazepine, or cisapride under steady-state conditions. The results of these studies indicated that sertraline did not increase plasma concentrations of terfenadine, carbamazepine, or cisapride. These data indicate that sertraline’s extent of inhibition of P450 3A4 activity is not likely to be of clinical significance. Results of the interaction study with cisapride indicate that sertraline 200 mg (q.d.) induces the metabolism of cisapride (cisapride AUC and Cmax were reduced by about 35%).","","ncit:positive","ncit:quantitative",,"cisapride","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","sertraline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","UNK","UNK","Unk","QD","Oral","Unk","Unk","35","Percent","Decrease","Unk","UNK","UNK","35","Percent","Decrease","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:42:22 -0400","drug-drug-interaction","evidence-supports","nical Pharmacology (12.3) ] . ","No dose adjustment for EMSAM is needed when EMSAM is used concomitantly with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and CYP3A4 inhibitors (e.g., ketoconazole). No clinically meaningful change in selegiline exposure was seen when EMSAM was co-administered with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and ketoconazole [see Clinical Pharmacology (12.3)]. ","","ncit:negative","ncit:Qualitative",,"risperidone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","EMSAM","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:42:05 -0500","DDI-clinical-trial","evidence-supports","Potential for Other Drugs to Affect WELLBUTRIN XL ","In vitro studies indicate that bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists for drug interactions between WELLBUTRIN XL and drugs that are inhibitors or inducers of CYP2B6. In addition, in vitro studies suggest that paroxetine, sertraline, norfluoxetine, fluvoxamine, and nelfinavir, inhibit the hydroxylation of bupropion.","","ncit:positive","ncit:quantitative",,"sertraline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","bupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b8881a81-75d7-43e8-825f-37c352c146dc.html","2015-11-04 14:21:12 -0500","drug-drug-interaction","evidence-supports","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquine hydroxylase) is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small or quite large (8 fold increase in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics, propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:24:24 -0500","drug-drug-interaction","evidence-supports","XL and drugs that are inhibitors or inducers of CYP2B6. Inhibitors of CYP2B6 ","Ticlopidine and Clopidogrel: Concomitant treatment with these drugs can increase bupropion exposures but decrease hydroxybupropion exposure. Based on clinical response, dosage adjustment of WELLBUTRIN XL may be necessary when coadministered with CYP2B6 inhibitors (e.g., ticlopidine or clopidogrel) [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"Clopidogrel","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"hydroxybupropion","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/0177d783-773c-41bf-9db9-eb7e5c64474a.html","2015-11-05 10:40:12 -0500","drug-drug-interaction","evidence-supports","Drugs Metabolized by P450 2D6 ","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7-10% of caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of the isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.","","ncit:positive","ncit:Qualitative",,"tricyclic antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","sertraline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:13:14 -0500","DDI-clinical-trial","evidence-supports","erythrohydrobupropion decreased by 68%. ","In another healthy volunteer study, lopinavir 400 mg/ritonavir 100 mg twice daily decreased bupropion AUC and Cmax by 57%. The AUC and Cmax of hydroxybupropion metabolite were decreased by 50% and 31%, respectively.","","ncit:positive","ncit:quantitative","Combined lopinavir/ritonavir dose","bupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","ritonavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","UNK","UNK","Unk","BID","Oral","Unk","Unk","57","Percent","Decrease","Unk","UNK","UNK","57","Percent","Decrease","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-09-14 11:32:07 -0400","drug-drug-interaction","evidence-supports","d. Fosamprenavir / Ritonavir ","Coadministration of fosamprenavir/ritonavir with paroxetine significantly decreased plasma levels of paroxetine. Any dose adjustment should be guided by clinical effect (tolerability and efficacy).","","ncit:positive","ncit:Qualitative",,"ritonavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","paroxetine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/55816042-946d-4bec-9461-bd998628ff45.html","2015-10-14 11:57:06 -0400","drug-drug-interaction","evidence-supports","tantly administered rifampin. ","Rifampin has been reported to substantially decrease the plasma concentrations of the following antiviral drugs: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir. These antiviral drugs must not be co-administered with rifampin. (See CONTRAINDICATIONS.) ","","ncit:positive","ncit:Qualitative",,"Rifampin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","saquinavir","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 13:28:11 -0400","DDI-clinical-trial","evidence-supports","","Carbamazepine Carbamazepine is an enzyme inducer and typically causes decreases in drug exposure; however, approximately 2-fold increased systemic exposure of selegiline and its metabolites, L-amphetamine and L-methamphetamine were seen after single application of EMSAM 6 mg per 24 hours in subjects who had received carbamazepine (400 mg per day) for 14 days. Changes in plasma selegiline concentrations were nearly 2-fold and variable across the subject population. Such increases may increase the risk of a hypertensive crisis when carbamazepine is used with EMSAM at any dose [see Contraindications (4), Warnings and Precautions (5.3) and Drug Interaction (7.4)].","","ncit:positive","ncit:quantitative",,"methamphetamine","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","Unk","carbamazepine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","6","UNK","UNK","Unk","SD","transdermal","1","Unk","2","Fold","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:38:36 -0400","DDI-clinical-trial","evidence-supports"," Tacrine ","In a study of 13 healthy, male volunteers, a single 40 mg dose of tacrine added to fluvoxamine 100 mg/day administered at steady-state was associated with 5- and 8-fold increases in tacrine Cmax and AUC, respectively, compared to the administration of tacrine alone. Five subjects experienced nausea, vomiting, sweating, and diarrhea following coadministration, consistent with the cholinergic effects of tacrine. ","","ncit:positive","ncit:quantitative",,"fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","tacrine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","40","SD","Oral","1","Daily","Oral","Unk","13","8","Fold","Increase","Unk","UNK","UNK","5","Fold","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/ea35caf8-c8c8-481a-97a2-25f68cbc240b.html","2015-09-29 09:04:36 -0400","drug-drug-interaction","evidence-supports","e in plasma AUC of the TCA ). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","phenothiazines","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports"," Drugs Metabolized by CYP2D6 ","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","","ncit:positive","ncit:Qualitative",,"Bupropion","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"risperidone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/55816042-946d-4bec-9461-bd998628ff45.html","2015-10-14 11:57:06 -0400","drug-drug-interaction","evidence-supports","tantly administered rifampin. ","Rifampin has been reported to substantially decrease the plasma concentrations of the following antiviral drugs: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir. These antiviral drugs must not be co-administered with rifampin. (See CONTRAINDICATIONS.) ","","ncit:positive","ncit:Qualitative",,"Rifampin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","fosamprenavir","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/829a4f51-c882-4b64-81f3-abfb03a52ebe.html","2015-10-29 09:24:53 -0400","DDI-clinical-trial","evidence-supports"," Drugs Metabolized by CYP2C9 ","Results of in vitro studies demonstrate that duloxetine does not inhibit activity. In a clinical study, the pharmacokinetics of S-warfarin, a CYP2C9 substrate, were not significantly affected by duloxetine [see DRUG INTERACTIONS (7.4)]. ","","ncit:negative","ncit:quantitative",,"duloxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","warfarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a16297df-3158-48db-85e5-5cd506885556.html","2015-09-29 09:27:10 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine, cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f356c1b-96bd-4ef1-960c-91cf4905e6b1.html","2015-09-10 14:36:47 -0400","drug-drug-interaction","evidence-supports","","Antipsychotics — Some clinical data suggests a possible pharmacodynamic and/or pharmacokinetic interaction between SSRIs and antipsychotics. Elevation of blood levels of haloperidol and clozapine has been observed in patients receiving concomitant fluoxetine. ","","ncit:positive","ncit:Qualitative",,"clozapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:30:38 -0500","DDI-clinical-trial","evidence-supports"," 7.10 Pimozide and Celexa ","In a controlled study, a single dose of pimozide 2 mg co-administered with racemic citalopram 40 mg given once daily for 11 days was associated with a mean increase in QTc values of approximately 10 msec compared to pimozide given alone. Racemic citalopram did not alter the mean AUC or Cmax of pimozide. The mechanism of this pharmacodynamic interaction is not known. ","","ncit:negative","ncit:quantitative",,"pimozide","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","2","citalopram","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","SD","Oral","1","Daily","Oral","11","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-10-28 15:23:30 -0400","DDI-clinical-trial","evidence-supports","s not studied. Phenobarbital ","Phenobarbital induces many cytochrome P450 (oxidative) enzymes. When a single oral 30 mg dose of paroxetine was administered at phenobarbital steady state (100 mg once daily for 14 days), paroxetine AUC and T½ were reduced (by an average of 25% and 38%, respectively) compared to paroxetine administered alone. The effect of paroxetine on phenobarbital pharmacokinetics was not studied. Since paroxetine exhibits nonlinear pharmacokinetics, the results of this study may not address the case where the 2 drugs are both being chronically dosed. No initial dosage adjustment of paroxetine is considered necessary when coadministered with phenobarbital; any subsequent adjustment should be guided by clinical effect.","","ncit:positive","ncit:quantitative",,"paroxetine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","30","phenobarbital","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","SD","Oral","1","Daily","Oral","14","Unk","25","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK","38","Percent","Decrease" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:48:13 -0500","DDI-clinical-trial","evidence-supports"," CYP3A4 and -2C19 Inhibitors ","In vitro studies indicated that CYP3A4 and -2C19 are the primary enzymes involved in the metabolism of escitalopram. However, coadministration of escitalopram (20 mg) and ritonavir (600 mg), a potent inhibitor of CYP3A4, did not significantly affect the pharmacokinetics of escitalopram. Because escitalopram is metabolized by multiple enzyme systems, inhibition of a single enzyme may not appreciably decrease escitalopram clearance.","","ncit:negative","ncit:quantitative",,"ritonavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","escitalopram","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","20","UNK","Oral","Unk","UNK","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:56:02 -0500","DDI-clinical-trial","evidence-supports","nefazodone by other highly bound drugs. ","Warfarin – There were no effects on the prothrombin or bleeding times or upon the pharmacokinetics of R-warfarin when nefazodone (200 mg BID) was administered for 1 week to subjects who had been pretreated for 2 weeks with warfarin. Although the coadministration of nefazodone did decrease the subjects’ exposure to S-warfarin by 12%, the lack of effects on the prothrombin and bleeding times indicates this modest change is not clinically significant. Although these results suggest no adjustments in warfarin dosage are required when nefazodone is administered to patients stabilized on warfarin, such patients should be monitored as required by standard medical practices.","","ncit:negative","ncit:quantitative","12% exposure decrease","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","warfarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","14","BID","Oral","7","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 14:28:56 -0400","DDI-clinical-trial","evidence-supports"," Alprazolam ","When fluvoxamine maleate (100 mg q.d.) and alprazolam (1 mg q.i.d.) were coadministered to steady state, plasma concentrations and other pharmacokinetic parameters (AUC, Cmax, T½) of alprazolam were approximately twice those observed when alprazolam was administered alone; oral clearance was reduced by about 50%. The elevated plasma alprazolam concentrations resulted in decreased psychomotor performance and memory. This interaction, which has not been investigated using higher doses of fluvoxamine, may be more pronounced if a 300 mg daily dose is coadministered, particularly since fluvoxamine exhibits non-linear pharmacokinetics over the dosage range 100 mg to 300 mg. If alprazolam is coadministered with fluvoxamine maleate tablets, the initial alprazolam dosage should be at least halved and titration to the lowest effective dose is recommended. No dosage adjustment is required for fluvoxamine maleate tablets. ","","ncit:positive","ncit:quantitative",,"fluvoxamine maleate","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","alprazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","1","QID","Oral","Unk","QD","Oral","Unk","Unk","2","Fold","Increase","50","Percent","Decrease","2","Fold","Increase","2","Fold","Increase" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:45:24 -0500","DDI-clinical-trial","evidence-supports","Interaction With Carbamazepine ","The coadministration of carbamazepine 200 mg BID with nefazodone 200 mg BID, at steady state for both drugs, resulted in almost 95% reductions in AUCs for nefazodone and hydroxynefazodone, likely resulting in insufficient plasma nefazodone and hydroxynefazodone concentrations for achieving an antidepressant effect for nefazodone. Consequently, it is recommended that nefazodone not be used in combination with carbamazepine (see CONTRAINDICATIONS and PRECAUTIONS).","","ncit:positive","ncit:quantitative",,"carbamazepine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","hydroxynefazodone","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","BID","Oral","Unk","Unk","95","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:52:07 -0500","DDI-clinical-trial","evidence-supports","and AUC values of hydroxybupropion by 32% and 24%, respectively. ","Cimetidine: Following oral administration of bupropion 300 mg with and without cimetidine 800 mg in 24 healthy young male volunteers, the pharmacokinetics of bupropion and hydroxybupropion were unaffected. However, there were 16% and 32% increases in the AUC and Cmax, respectively, of the combined moieties of threohydrobupropion and erythrohydrobupropion.","","ncit:negative","ncit:quantitative",,"cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","300","hydroxybupropion","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","Oral","Unk","24","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:05:45 -0500","DDI-clinical-trial","evidence-supports","Inducers of CYP2B6 Ritonavir and Lopinavir : ","In a healthy volunteer study, ritonavir 100 mg twice daily reduced the AUC and Cmax of bupropion by 22% and 21%, respectively. The exposure of the hydroxybupropion metabolite was decreased by 23%, the threohydrobupropion decreased by 38%, and the erythrohydrobupropion decreased by 48%. ","","ncit:positive","ncit:quantitative","Exposure decreased 48%","erythrohydrobupropion","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","Unk","ritonavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","UNK","UNK","Unk","BID","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:04:06 -0500","DDI-clinical-trial","evidence-supports","I","n a healthy volunteer study, ritonavir 100 mg twice daily reduced the AUC and Cmax of bupropion by 22% and 21%, respectively. The exposure of the hydroxybupropion metabolite was decreased by 23%, the threohydrobupropion decreased by 38%, and the erythrohydrobupropion decreased by 48%. ","","ncit:positive","ncit:quantitative","Exposure decreased by 23%","ritonavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","hydroxybupropion","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","BID","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","7.1 Potential Interactions with Drugs that Inhibit or are Metabolized by Cytochrome P450 Isoenzymes ","Multiple hepatic cytochrome P450 isoenzymes are involved in the oxidative biotransformation of a large number of structurally different drugs and endogenous compounds. The available knowledge concerning the relationship of fluvoxamine and the cytochrome P450 isoenzyme system has been obtained mostly from pharmacokinetic interaction studies conducted in healthy volunteers, but some preliminary in vitro data are also available. Based on a finding of substantial interactions of fluvoxamine with certain of these drugs [see later parts of this section and also Warnings and Precautions (5)] and limited in vitro data for CYP3A4, it appears that fluvoxamine inhibits several cytochrome P450 isoenzymes that are known to be involved in the metabolism of other drugs such as: CYP1A2 (e.g., warfarin, theophylline, propranolol, tizanidine), CYP2C9 (e.g., warfarin), CYP3A4 (e.g., alprazolam), and CYP2C19 (e.g., omeprazole). ","","ncit:positive","ncit:Qualitative",,"fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"propranolol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-09-29 11:28:40 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type IC antiarrhythmics propafenone and flecainide). While all the SSRIs, e.g., fluoxetine, sertraline, paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-10-29 11:30:54 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type IC antiarrhythmics propafenone and flecainide). While all the SSRIs, e.g., fluoxetine, sertraline, paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction",,"propafenone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:15:31 -0500","DDI-clinical-trial","evidence-supports","metabolite were decreased by 50% and 31%, respectively. ","Efavirenz: In a study of healthy volunteers, efavirenz 600 mg once daily for 2 weeks reduced the AUC and Cmax of bupropion by approximately 55% and 34%, respectively. The AUC of hydroxybupropion was unchanged, whereas Cmax of hydroxybupropion was increased by 50%.","","ncit:positive","ncit:quantitative",,"bupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","efavirenz","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","UNK","UNK","Unk","Daily","Oral","14","Unk","55","Percent","Decrease","Unk","UNK","UNK","34","Percent","Decrease","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports"," Drugs Metabolized by CYP2D6 ","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","","ncit:positive","ncit:Qualitative",,"Bupropion","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"antiarrhythmics","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:29:30 -0400","DDI-clinical-trial","evidence-supports"," Mexiletine ","The effect of steady-state fluvoxamine (50 mg b.i.d. for 7 days) on the single dose pharmacokinetics of mexiletine (200 mg) was evaluated in six healthy Japanese males. The clearance of mexiletine was reduced by 38% following coadministration with fluvoxamine compared to mexiletine alone. If fluvoxamine and mexiletine are coadministered, serum mexiletine levels should be monitored. ","","ncit:positive","ncit:quantitative",,"mexiletine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","200","fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","50","SD","Oral","1","BID","Oral","7","6","Unk","UNK","UNK","38","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:18:31 -0500","DDI-clinical-trial","evidence-supports","with other drugs metabolized by CYP2D6 has not been formally studied. ","Citalopram: Although citalopram is not primarily metabolized by CYP2D6, in one study bupropion increased the Cmax and AUC of citalopram by 30% and 40%, respectively. ","","ncit:positive","ncit:quantitative",,"citalopram","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","bupropion","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","40","Percent","Increase","Unk","UNK","UNK","30","Percent","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e338e89-3cf2-48eb-b6e2-a06c608c6513.html","2015-08-20 11:10:08 -0400","DDI-clinical-trial","evidence-supports","nical Pharmacology (12.3) ] . ","In a CYP2C8 drug-drug interaction trial in healthy subjects, the AUC of pioglitazone (CYP2C8 substrate) was increased by 46% when pioglitazone was given together with a single dose of 1,000 mg abiraterone acetate. Therefore, patients should be monitored closely for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with ZYTIGA [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:quantitative",,"abiraterone acetate","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","pioglitazone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","1000","UNK","UNK","Unk","SD","UNK","1","Unk","46","Percent","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 14:27:00 -0400","drug-drug-interaction","evidence-supports",", etc.) should be used with caution because the clearance of these drugs is likely to be reduced by fluvoxamine . ","The clearance of benzodiazepines metabolized by glucuronidation (e.g., lorazepam, oxazepam, temazepam) is unlikely to be affected by fluvoxamine. ","","ncit:negative","ncit:Qualitative",,"oxazepam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:38:35 -0500","DDI-clinical-trial","evidence-supports","","Lithium - Coadministration of Celexa (40 mg/day for 10 days) and lithium (30 mmol/day for 5 days) had no significant effect on the pharmacokinetics of citalopram or lithium. Nevertheless, plasma lithium levels should be monitored with appropriate adjustment to the lithium dose in accordance with standard clinical practice. Because lithium may enhance the serotonergic effects of citalopram, caution should be exercised when Celexa and lithium are coadministered.","","ncit:negative","ncit:quantitative",,"lithium","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","30 mmol","citalopram","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","Daily","IV","5","Daily","Oral","10","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f356c1b-96bd-4ef1-960c-91cf4905e6b1.html","2015-09-10 14:36:47 -0400","drug-drug-interaction","evidence-supports","","Lithium — There have been reports of both increased and decreased lithium levels when lithium was used concomitantly with fluoxetine. Cases of lithium toxicity and increased serotonergic effects have been reported. Lithium levels should be monitored when these drugs are administered concomitantly [see Warnings and Precautions (5.2)]. ","","ncit:positive","ncit:Qualitative",,"fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","Lithium","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:38:35 -0500","DDI-clinical-trial","evidence-supports","","Warfarin - Administration of 40 mg/day Celexa for 21 days did not affect the pharmacokinetics of warfarin, a CYP3A4 substrate. Prothrombin time was increased by 5%, the clinical significance of which is unknown.","","ncit:negative","ncit:quantitative",,"Celexa","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","40","warfarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","Daily","Oral","21","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-10-28 15:23:30 -0400","DDI-clinical-trial","evidence-supports","bolizing enzymes. Cimetidine ","Cimetidine inhibits many cytochrome P450 (oxidative) enzymes. In a study where paroxetine (30 mg once daily) was dosed orally for 4 weeks, steady-state plasma concentrations of paroxetine were increased by approximately 50% during coadministration with oral cimetidine (300 mg three times daily) for the final week. Therefore, when these drugs are administered concurrently, dosage adjustment of paroxetine after the 20 mg starting dose should be guided by clinical effect. The effect of paroxetine on cimetidine’s pharmacokinetics was not studied.","","ncit:positive","ncit:quantitative",,"cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","300","paroxetine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","30","Daily","Oral","28","TID","Oral","7","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports"," Drugs Metabolized by CYP2D6 ","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","","ncit:positive","ncit:Qualitative",,"Bupropion","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"sertraline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:38:24 -0400","drug-drug-interaction","evidence-supports","AUBAGIO on CYP2C8 substrates ","Teriflunomide is an inhibitor of CYP2C8 in vivo. In patients taking AUBAGIO, exposure of drugs metabolized by CYP2C8 (e.g., paclitaxel, pioglitazone, repaglinide, rosiglitazone) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP2C8 as required [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","paclitaxel","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-10-28 14:38:28 -0400","DDI-clinical-trial","evidence-supports","). Drug-Drug Interactions  ","In vitro drug interaction studies reveal that paroxetine inhibits CYP2D6. Clinical drug interaction studies have been performed with substrates of CYP2D6 and show that paroxetine can inhibit the metabolism of drugs metabolized by CYP2D6 including desipramine, risperidone, and atomoxetine (see PRECAUTIONS: Drug Interactions).","","ncit:positive","ncit:quantitative",,"desipramine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a16297df-3158-48db-85e5-5cd506885556.html","2015-09-29 09:27:10 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine, cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:49:25 -0400","DDI-clinical-trial","evidence-supports"," Diazepam ","Concomitant administration of diazepam (15 mg) had a minimal effect on plasma levels of mirtazapine (15 mg) in 12 healthy subjects. However, the impairment of motor skills produced by REMERON has been shown to be additive with those caused by diazepam. Accordingly, patients should be advised to avoid diazepam and other similar drugs while taking REMERON.","","ncit:negative","ncit:quantitative",,"diazepam","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","15","mirtazapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","15","UNK","Oral","Unk","UNK","Oral","Unk","12","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:15:20 -0400","DDI-clinical-trial","evidence-supports","","Phenylpropanolamine (PPA) In subjects who had received EMSAM 6 mg per 24 hours for 9 days, co-administration with PPA (25 mg every 4 hours for 24 hours) did not affect the pharmacokinetics of PPA. There was a higher incidence of significant blood pressure elevations with the co-administration of EMSAM and PPA than with PPA alone, suggesting a possible pharmacodynamic interaction [see Drug Interactions (7.4) and (7.5)]. ","","ncit:negative","ncit:quantitative","PPA given every 4 hours for 24 hours.","Phenylpropanolamine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","25","EMSAM","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","6","UNK","Oral","Unk","Daily","transdermal","9","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:48:13 -0400","DDI-clinical-trial","evidence-supports"," Paroxetine ","In an in vivo interaction study in healthy, CYP2D6 extensive metabolizer patients (n=24), mirtazapine (30 mg/day), at steady state, did not cause relevant changes in the pharmacokinetics of steady state paroxetine (40 mg/day), a CYP2D6 inhibitor.","","ncit:negative","ncit:quantitative",,"paroxetine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","40","mirtazapine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","30","Daily","Oral","Unk","Daily","Oral","Unk","24","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e338e89-3cf2-48eb-b6e2-a06c608c6513.html","2015-08-20 11:17:13 -0400","DDI-clinical-trial","evidence-supports","CYP2C9, CYP2C19 and CYP3A4/5. ","In an in vivo drug-drug interaction trial, the Cmax and AUC of dextromethorphan (CYP2D6 substrate) were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily (plus prednisone 5 mg twice daily). The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold [see Drug Interactions (7.2)].","","ncit:positive","ncit:quantitative",,"dextrorphan","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","1000","abiraterone acetate","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","Daily","UNK","Unk","Unk","1.3","Fold","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c66a11c1-3093-45ef-b348-3b196c05ba0c.html","2015-10-01 10:31:02 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dosage regimen of a TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 14:00:44 -0500","DDI-clinical-trial","evidence-supports","","Ketoconazole - Combined administration of Celexa (40 mg) and ketoconazole (200 mg) decreased the Cmax and AUC of ketoconazole by 21% and 10%, respectively, and did not significantly affect the pharmacokinetics of citalopram.","","ncit:positive","ncit:quantitative",,"citalopram","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","ketoconazole","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","200","UNK","Oral","Unk","UNK","Oral","Unk","Unk","21","Percent","Decrease","10","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:43:14 -0500","drug-drug-interaction","evidence-supports","Potential Terfenadine, Astemizole, Cisapride, and Pimozide Interactions ","Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. Increased plasma concentrations of terfenadine, astemizole, cisapride, and pimozide are associated with QT prolongation and with rare cases of serious cardiovascular adverse events, including death, due principally to ventricular tachycardia of the torsade de pointes type. Nefazodone has been shown in vitro to be an inhibitor of CYP3A4. Consequently, it is recommended that nefazodone not be used in combination with either terfenadine, astemizole, cisapride, or pimozide (see CONTRAINDICATIONS and PRECAUTIONS).","","ncit:positive","ncit:Qualitative",,"pimozide","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:30:13 -0500","drug-drug-interaction","evidence-supports"," Drugs Metabolized by CYP2D6 ","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","","ncit:positive","ncit:Qualitative",,"Bupropion","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"venlafaxine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports"," Drugs Metabolized by CYP2D6 ","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","","ncit:positive","ncit:Qualitative",,"haloperidol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Bupropion","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:48:50 -0400","drug-drug-interaction","evidence-supports","nsporter 3 (OAT3) substrates ","Teriflunomide inhibits the activity of OAT3 in vivo. In patients taking AUBAGIO, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) which are OAT3 substrates as required [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"cefaclor","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f356c1b-96bd-4ef1-960c-91cf4905e6b1.html","2015-11-02 16:12:40 -0500","DDI-clinical-trial","evidence-supports","","Drugs Metabolized by CYP3A4 — In an in vivo interaction study involving coadministration of fluoxetine with single doses of terfenadine (a CYP3A4 substrate), no increase in plasma terfenadine concentrations occurred with concomitant fluoxetine. ","","ncit:negative","ncit:quantitative",,"fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","terfenadine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","SD","UNK","1","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e17dc299-f52d-414d-ab6e-e809bd6f8acb.html","2015-11-04 14:14:49 -0500","drug-drug-interaction","evidence-supports","(TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports"," Drugs Metabolized by CYP2D6 ","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","","ncit:positive","ncit:Qualitative",,"Bupropion","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"thioridazine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:27:26 -0500","DDI-clinical-trial","evidence-supports"," 7.9 Lithium ","Coadministration of racemic citalopram (40 mg/day for 10 days) and lithium (30 mmol/day for 5 days) had no significant effect on the pharmacokinetics of citalopram or lithium. Nevertheless, plasma lithium levels should be monitored with appropriate adjustment to the lithium dose in accordance with standard clinical practice. Because lithium may enhance the serotonergic effects of escitalopram, caution should be exercised when Lexapro and lithium are coadministered. ","","ncit:negative","ncit:quantitative",,"citalopram","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","lithium","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","30 mmol","Daily","IV","5","Daily","Oral","10","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports"," be an inhibitor of P450 2D6. ","The plasma concentration of imipramine may increase when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decrease by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), and adjustment of the dosage of imipramine may therefore be necessary.","","ncit:positive","ncit:Qualitative",,"cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","imipramine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:38:35 -0500","DDI-clinical-trial","evidence-supports","","Theophylline - Combined administration of Celexa (40 mg/day for 21 days) and the CYP1A2 substrate theophylline (single dose of 300 mg) did not affect the pharmacokinetics of theophylline. The effect of theophylline on the pharmacokinetics of citalopram was not evaluated.","","ncit:negative","ncit:quantitative",,"theophylline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","300","Celexa","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","40","SD","Oral","1","Daily","Oral","21","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1809bcb4-5fcc-45ca-986a-4fa5edcd4b5e.html","2015-09-29 11:41:50 -0400","drug-drug-interaction","evidence-supports","er tricyclic antidepressants. ","The plasma concentration of CMI has been reported to be increased by the concomitant administration of haloperidol; plasma levels of several closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of methylphenidate or hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by the concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin), and such an effect may be anticipated with CMI as well. Administration of CMI has been reported to increase the plasma levels of phenobarbital, if given concomitantly (see CLINICAL PHARMACOLOGY, Interactions).","","ncit:positive","ncit:Qualitative",,"phenytoin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","tricyclic antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 11:48:50 -0400","drug-drug-interaction","evidence-supports","nsporter 3 (OAT3) substrates ","Teriflunomide inhibits the activity of OAT3 in vivo. In patients taking AUBAGIO, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) which are OAT3 substrates as required [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"zidovudine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:24:24 -0500","drug-drug-interaction","evidence-supports","XL and drugs that are inhibitors or inducers of CYP2B6. Inhibitors of CYP2B6 ","Ticlopidine and Clopidogrel: Concomitant treatment with these drugs can increase bupropion exposures but decrease hydroxybupropion exposure. Based on clinical response, dosage adjustment of WELLBUTRIN XL may be necessary when coadministered with CYP2B6 inhibitors (e.g., ticlopidine or clopidogrel) [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"bupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Ticlopidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","DDI-clinical-trial","evidence-supports"," Lorazepam ","A study of multiple doses of fluvoxamine maleate (50 mg b.i.d.) in healthy male volunteers (N = 12) and a single dose of lorazepam (4 mg single dose) indicated no significant pharmacokinetic interaction. On average, both lorazepam alone and lorazepam with fluvoxamine produced substantial decrements in cognitive functioning; however, the coadministration of fluvoxamine and lorazepam did not produce larger mean decrements compared to lorazepam alone. ","","ncit:negative","ncit:quantitative",,"fluvoxamine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","50","lorazepam","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","4","BID","Oral","Unk","SD","Oral","1","12","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:56:21 -0500","DDI-clinical-trial","evidence-supports","","Triazolam - Combined administration of Celexa (titrated to 40 mg/day for 28 days) and the CYP3A4 substrate triazolam (single dose of 0.25 mg) did not significantly affect the pharmacokinetics of either citalopram or triazolam.","","ncit:negative","ncit:quantitative",,"citalopram","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","triazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","0.25","SD","Oral","1","Daily","Oral","28","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports"," be an inhibitor of P450 2D6. ","The plasma concentration of imipramine may increase when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decrease by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), and adjustment of the dosage of imipramine may therefore be necessary.","","ncit:positive","ncit:Qualitative",,"imipramine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","barbiturates","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-09-14 11:31:14 -0400","drug-drug-interaction","evidence-supports","taken with caution. Diazepam ","Under steady-state conditions, diazepam does not appear to affect paroxetine kinetics. The effects of paroxetine on diazepam were not evaluated.","","ncit:negative","ncit:Qualitative",,"paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","diazepam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","DDI-clinical-trial","evidence-supports","s (7) ] . CYP1A2 Substrates ","Repeated doses of teriflunomide decreased mean Cmax and AUC of caffeine by 18% and 55%, respectively, suggesting that teriflunomide may be a weak inducer of CYP1A2 in vivo.","","ncit:positive","ncit:quantitative",,"caffeine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","55","Percent","Increase","Unk","UNK","UNK","18","Percent","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:42:22 -0400","drug-drug-interaction","evidence-supports","nical Pharmacology (12.3) ] . ","No dose adjustment for EMSAM is needed when EMSAM is used concomitantly with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and CYP3A4 inhibitors (e.g., ketoconazole). No clinically meaningful change in selegiline exposure was seen when EMSAM was co-administered with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and ketoconazole [see Clinical Pharmacology (12.3)]. ","","ncit:negative","ncit:Qualitative",,"levothyroxine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","EMSAM","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:32:33 -0500","DDI-clinical-trial","evidence-supports"," 7.15 Triazolam ","Combined administration of racemic citalopram (titrated to 40 mg/day for 28 days) and the CYP3A4 substrate triazolam (single dose of 0.25 mg) did not significantly affect the pharmacokinetics of either citalopram or triazolam.","","ncit:negative","ncit:quantitative",,"citalopram","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","40","triazolam","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","0.25","Daily","Oral","28","SD","Oral","1","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:21:18 -0500","DDI-clinical-trial","evidence-supports"," by 30% and 40%, respectively. "," Lamotrigine: Multiple oral doses of bupropion had no statistically significant effects on the single-dose pharmacokinetics of lamotrigine in 12 healthy volunteers.","","ncit:negative","ncit:quantitative",,"lamotrigine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","bupropion","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","SD","Oral","1","UNK","Oral","Unk","12","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","metabolism have not been studied. ","A clinically significant fluvoxamine interaction is possible with drugs having a narrow therapeutic ratio such as pimozide, warfarin, theophylline, certain benzodiazepines, omeprazole and phenytoin. If fluvoxamine maleate tablets are to be administered together with a drug that is eliminated via oxidative metabolism and has a narrow therapeutic window, plasma levels and/or pharmacodynamic effects of the latter drug should be monitored closely, at least until steady-state conditions are reached [see Contraindications (4) and Warnings and Precautions (5)]. ","","ncit:positive","ncit:Qualitative",,"theophylline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:42:22 -0400","drug-drug-interaction","evidence-supports","nical Pharmacology (12.3) ] . ","No dose adjustment of alprazolam, ibuprofen, levothyroxine, olanzapine, risperdione, warfarin, or strong CYP3A4 inhibitors (e.g., ketoconazole) is necessary when these drugs are used in combination with EMSAM. EMSAM had no clinically relevant effect on pharmacokinetics of these drugs.","","ncit:negative","ncit:Qualitative",,"EMSAM","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","","risperdione","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 12:50:04 -0400","drug-drug-interaction","evidence-supports"," B3 (OATP1B1/1B3) substrates ","Teriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo. For a patient taking AUBAGIO, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking AUBAGIO [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"rosuvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 12:50:04 -0400","drug-drug-interaction","evidence-supports"," B3 (OATP1B1/1B3) substrates ","Teriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo. For a patient taking AUBAGIO, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking AUBAGIO [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"atorvastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:36:27 -0400","DDI-clinical-trial","evidence-supports","I","n a controlled study of a single dose (2 mg) of pimozide, 200 mg sertraline (q.d.) co-administration to steady state was associated with a mean increase in pimozide AUC and Cmax of about 40%, but was not associated with any changes in EKG. Since the highest recommended pimozide dose (10 mg) has not been evaluated in combination with sertraline, the effect on QT interval and PK parameters at doses higher than 2 mg at this time are not known. While the mechanism of this interaction is unknown, due to the narrow therapeutic index of pimozide and due to the interaction noted at a low dose of pimozide, concomitant administration of sertraline and pimozide should be contraindicated (see ","","ncit:positive","ncit:quantitative",,"sertraline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","pimozide","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","2","SD","Oral","1","QD","Oral","Unk","Unk","40","Percent","Increase","Unk","UNK","UNK","40","Percent","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:42:22 -0400","drug-drug-interaction","evidence-supports","nical Pharmacology (12.3) ] . ","No dose adjustment for EMSAM is needed when EMSAM is used concomitantly with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and CYP3A4 inhibitors (e.g., ketoconazole). No clinically meaningful change in selegiline exposure was seen when EMSAM was co-administered with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and ketoconazole [see Clinical Pharmacology (12.3)]. ","","ncit:negative","ncit:Qualitative",,"EMSAM","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","","ibuprofen","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","drug-drug-interaction","evidence-supports","see Drug Interactions (7) ] . ","Teriflunomide did not affect the pharmacokinetics of bupropion (a CYP2B6 substrate), midazolam (a CYP3A4 substrate), S-warfarin (a CYP2C9 substrate), omeprazole (a CYP2C19 substrate), and metoprolol (a CYP2D6 substrate).","","ncit:negative","ncit:Qualitative",,"Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","omeprazole","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:41:13 -0400","drug-drug-interaction","evidence-supports"," Ketoconazole ","In healthy, male, Caucasian patients (n=24), coadministration of the potent CYP3A4 inhibitor ketoconazole (200 mg b.i.d. for 6.5 days) increased the peak plasma levels and the AUC of a single 30-mg dose of mirtazapine by approximately 40% and 50%, respectively. Caution should be exercised when coadministering mirtazapine with potent CYP3A4 inhibitors, HIV protease inhibitors, azole antifungals, erythromycin, or nefazodone.","","ncit:positive","ncit:Qualitative",,"erythromycin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","mirtazapine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/51ff7db5-aaf9-4c3c-86e6-958ebf16b60f.html","2015-11-06 15:34:44 -0500","DDI-clinical-trial","evidence-supports","). Nefazodone hydrochloride tablets are also contraindicated in patients who have demonstrated hypersensitivity to nefazodone hydrochloride, its inactive ingredients, or other phenylpiperazine antidepressants. ","The coadministration of triazolam and nefazodone causes a significant increase in the plasma level of triazolam (see WARNINGS and PRECAUTIONS), and a 75% reduction in the initial triazolam dosage is recommended if the two drugs are to be given together. Because not all commercially available dosage forms of triazolam permit a sufficient dosage reduction, the coadministration of triazolam and nefazodone should be avoided for most patients, including the elderly.","","ncit:positive","ncit:quantitative","Increased plasma level","nefazodone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","triazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/16a4a314-f97e-4e91-95e9-576a3773d284.html","2015-09-30 10:48:18 -0400","DDI-clinical-trial","evidence-supports","pran and 150 mg pregabalin . ","Warfarin-Steady-state milnacipran (200 mg/day) did not affect the pharmacokinetics of R-warfarin and S-warfarin or the pharmacodynamics (as assessed by measurement of prothrombin INR) of a single dose of 25 mg warfarin. The pharmacokinetics of Savella were not altered by warfarin. ","","ncit:negative","ncit:quantitative",,"Savella","dikbD2R:drug-product","dikbD2R:object-drug-of-interaction","25","warfarin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","Daily","tablet","Unk","SD","tablet","1","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-09-14 11:21:10 -0400","drug-drug-interaction","evidence-supports"," taking paroxetine . Lithium ","A multiple-dose study has shown that there is no pharmacokinetic interaction between paroxetine and lithium carbonate. However, due to the potential for serotonin syndrome, caution is advised when paroxetine is coadministered with lithium.","","ncit:negative","ncit:Qualitative",,"paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","lithium carbonate","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:34:37 -0500","drug-drug-interaction","evidence-supports"," Drugs Metabolized by CYP2D6 ","Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g. haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g. propafenone, and flecainide). When used concomitantly with WELLBUTRIN XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.","","ncit:positive","ncit:Qualitative",,"fluoxetine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Bupropion","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/f371258d-91b3-4b6a-ac99-434a1964c3af.html","2015-10-29 09:45:11 -0400","DDI-clinical-trial","evidence-supports","ther Drugs to Affect FETZIMA ","Dose adjustment is recommended when FETZIMA is co-administered with strong inhibitors of CYP3A4 (e.g. ketoconazole) [see Dosage and Administration (2.7)]. An in vivo study showed a clinically meaningful increase in levomilnacipran exposure when FETZIMA was co-administered with the CYP3A4 inhibitor ketoconazole (see Figure 1). ","","ncit:positive","ncit:quantitative",,"ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","levomilnacipran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c00d1607-ac36-457b-a34b-75ad74f9cf0a.html","2015-10-13 11:13:09 -0400","drug-drug-interaction","evidence-supports","ther Drugs to Affect INVIRASE ","The metabolism of saquinavir is mediated primarily by CYP3A. Additionally, saquinavir is a substrate for P-glycoprotein (P-gp). Therefore, drugs that affect CYP3A and/or P-gp may modify the pharmacokinetics of saquinavir. Coadministration with drugs that are potent inducers of CYP3A (e.g., phenobarbital, phenytoin, carbamazepine) may result in decreased plasma concentrations of saquinavir and reduced therapeutic effect.","","ncit:positive","ncit:Qualitative",,"saquinavir","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","phenytoin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:42:22 -0400","drug-drug-interaction","evidence-supports","nical Pharmacology (12.3) ] . ","No dose adjustment for EMSAM is needed when EMSAM is used concomitantly with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and CYP3A4 inhibitors (e.g., ketoconazole). No clinically meaningful change in selegiline exposure was seen when EMSAM was co-administered with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and ketoconazole [see Clinical Pharmacology (12.3)]. ","","ncit:negative","ncit:Qualitative",,"EMSAM","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","","alprazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/0177d783-773c-41bf-9db9-eb7e5c64474a.html","2015-11-05 10:40:12 -0500","drug-drug-interaction","evidence-supports","Drugs Metabolized by P450 2D6 ","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7-10% of caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of the isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.","","ncit:positive","ncit:Qualitative",,"tricyclic antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 14:27:00 -0400","drug-drug-interaction","evidence-supports"," Benzodiazepines ","Benzodiazepines metabolized by hepatic oxidation (e.g., alprazolam, midazolam, triazolam, etc.) should be used with caution because the clearance of these drugs is likely to be reduced by fluvoxamine. ","","ncit:positive","ncit:Qualitative",,"fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"triazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","drug-drug-interaction","evidence-supports","see Drug Interactions (7) ] . ","Teriflunomide did not affect the pharmacokinetics of bupropion (a CYP2B6 substrate), midazolam (a CYP3A4 substrate), S-warfarin (a CYP2C9 substrate), omeprazole (a CYP2C19 substrate), and metoprolol (a CYP2D6 substrate).","","ncit:negative","ncit:Qualitative",,"midazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:25:55 -0500","drug-drug-interaction","evidence-supports","Clinical Pharmacology (12.3) ]. Inducers of CYP2B6 ","Ritonavir, Lopinavir, and Efavirenz: Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure. Dosage increase of WELLBUTRIN XL may be necessary when coadministered with ritonavir, lopinavir, or efavirenz but should not exceed the maximum recommended dose [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:Qualitative",,"bupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","ritonavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-10-28 15:25:57 -0400","DDI-clinical-trial","evidence-supports","","Concomitant use of paroxetine with risperidone, a CYP2D6 substrate has also been evaluated. In 1 study, daily dosing of paroxetine 20 mg in patients stabilized on risperidone (4 to 8 mg/day) increased mean plasma concentrations of risperidone approximately 4-fold, decreased 9-hydroxyrisperidone concentrations approximately 10%, and increased concentrations of the active moiety (the sum of risperidone plus 9-hydroxyrisperidone) approximately 1.4-fold."," The effect of","ncit:positive","ncit:quantitative",,"paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","9-hydroxyrisperidone","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","Daily","Oral","Unk","Unk","10","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","drug-drug-interaction","evidence-supports","see Drug Interactions (7) ] . ","Teriflunomide did not affect the pharmacokinetics of bupropion (a CYP2B6 substrate), midazolam (a CYP3A4 substrate), S-warfarin (a CYP2C9 substrate), omeprazole (a CYP2C19 substrate), and metoprolol (a CYP2D6 substrate).","","ncit:negative","ncit:Qualitative",,"Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","warfarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/829a4f51-c882-4b64-81f3-abfb03a52ebe.html","2015-10-29 09:30:04 -0400","DDI-clinical-trial","evidence-supports","AIDs, Aspirin, and Warfarin) ","Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies of the case-control and cohort design that have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding have also shown that concurrent use of an NSAID or aspirin may potentiate this risk of bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs or SNRIs are co-administered with warfarin. Concomitant administration of warfarin (2 to 9 mg once daily) under steady state conditions with duloxetine 60 or 120 mg once daily for up to 14 days in healthy subjects (n=15) did not significantly change INR from baseline (mean INR changes ranged from 0.05 to +0.07). The total warfarin (protein bound plus free drug) pharmacokinetics (AUCτ,ss, Cmax,ss or tmax,ss) for both R- and S-warfarin were not altered by duloxetine. Because of the potential effect of duloxetine on platelets, patients receiving warfarin therapy should be carefully monitored when duloxetine is initiated or discontinued [see WARNINGS AND PRECAUTIONS (5.5)]. ","","ncit:negative","ncit:quantitative",,"duloxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","60 or 120","warfarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","2 to 9","Daily","UNK","Unk","Daily","Oral","14","15","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:48:28 -0500","DDI-clinical-trial","evidence-supports",", respectively. The exposures of hydroxybupropion were decreased. ","Prasugrel: In healthy subjects, prasugrel increased bupropion Cmax and AUC values by 14% and 18%, respectively, and decreased Cmax and AUC values of hydroxybupropion by 32% and 24%, respectively.","","ncit:positive","ncit:quantitative",,"prasugrel","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","bupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","18","Percent","Increase","Unk","UNK","UNK","14","Percent","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:40:32 -0500","DDI-clinical-trial","evidence-supports","Potential for Other Drugs to Affect WELLBUTRIN XL ","In vitro studies indicate that bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists for drug interactions between WELLBUTRIN XL and drugs that are inhibitors or inducers of CYP2B6. In addition, in vitro studies suggest that paroxetine, sertraline, norfluoxetine, fluvoxamine, and nelfinavir, inhibit the hydroxylation of bupropion.","","ncit:positive","ncit:quantitative",,"bupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:36:26 -0400","DDI-clinical-trial","evidence-supports","unknown. CNS Active Drugs– ","In a study comparing the disposition of intravenously administered diazepam before and after 21 days of dosing with either sertraline (50 to 200 mg/day escalating dose) or placebo, there was a 32% decrease relative to baseline in diazepam clearance for the sertraline group compared to a 19% decrease relative to baseline for the placebo group (p < 0.03). There was a 23% increase in Tmax for desmethyldiazepam in the sertraline group compared to a 20% decrease in the placebo group (p < 0.03). The clinical significance of these changes is unknown.","","ncit:positive","ncit:quantitative",,"sertraline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","50-200","diazepam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","IV","Unk","Daily","Oral","21","Unk","Unk","UNK","UNK","32","Percent","Decrease","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c66a11c1-3093-45ef-b348-3b196c05ba0c.html","2015-10-01 10:31:02 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dosage regimen of a TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"quinidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports"," be an inhibitor of P450 2D6. ","The plasma concentration of imipramine may increase when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decrease by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), and adjustment of the dosage of imipramine may therefore be necessary.","","ncit:positive","ncit:Qualitative",,"phenytoin","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","imipramine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/70b079e2-a1f7-4a93-8685-d60a4d7c1280.html","2015-10-14 12:07:40 -0400","DDI-clinical-trial","evidence-supports","ugs (see CONTRAINDICATIONS). ","Pimozide and Celexa: In a controlled study, a single dose of pimozide 2 mg coadministered with racemic citalopram 40 mg given once daily for 11 days was associated with a mean increase in QTc values of approximately 10 msec compared to pimozide given alone. Racemic citalopram did not alter the mean AUC or Cmax of pimozide. The mechanism of this pharmacodynamic interaction is not known. Concomitant use of Pimozide and Celexa or Lexapro is contraindicated (See CONTRAINDICATIONS).","","ncit:negative","ncit:quantitative",,"citalopram","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","pimozide","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","2","SD","Oral","1","Daily","Oral","11","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a9ff32c4-3bcf-4e51-ae8c-81ff0191ec35.html","2015-10-28 17:20:12 -0400","DDI-clinical-trial","evidence-supports","s of CYP3A4 ( ketoconazole ) ","CYP3A4 is a minor pathway for the metabolism of desvenlafaxine. In a clinical study, ketoconazole (200 mg BID) increased the area under the concentration vs. time curve (AUC) of desvenlafaxine (400 mg single dose) by about 43% and Cmax by about 8%. Concomitant use of desvenlafaxine with potent inhibitors of CYP3A4 may result in higher concentrations of desvenlafaxine. ","","ncit:positive","ncit:quantitative",,"desvenlafaxine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","400","ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","200","SD","Oral","1","BID","Oral","Unk","Unk","43","Percent","Increase","Unk","UNK","UNK","8","Percent","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-10-28 14:38:28 -0400","DDI-clinical-trial","evidence-supports","). Drug-Drug Interactions  ","In vitro drug interaction studies reveal that paroxetine inhibits CYP2D6. Clinical drug interaction studies have been performed with substrates of CYP2D6 and show that paroxetine can inhibit the metabolism of drugs metabolized by CYP2D6 including desipramine, risperidone, and atomoxetine (see PRECAUTIONS: Drug Interactions).","","ncit:positive","ncit:quantitative",,"risperidone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/0177d783-773c-41bf-9db9-eb7e5c64474a.html","2015-11-05 10:40:12 -0500","drug-drug-interaction","evidence-supports","Drugs Metabolized by P450 2D6 ","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7-10% of caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of the isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.","","ncit:positive","ncit:Qualitative",,"tricyclic antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction",,"quinidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 14:23:19 -0400","DDI-clinical-trial","evidence-supports","5.5 Potential Tizanidine Interaction ","Fluvoxamine is a potent inhibitor of CYP1A2 and tizanidine is a CYP1A2 substrate. The effect of fluvoxamine (100 mg daily for 4 days) on the pharmacokinetics and pharmacodynamics of a single 4 mg dose of tizanidine has been studied in ten healthy male subjects. Tizanidine Cmax was increased approximately 12-fold (range 5-fold to 32-fold), elimination half-life was increased by almost 3-fold, and AUC increased 33-fold (range 14-fold to 103-fold). The mean maximal effect on blood pressure was a 35 mm Hg decrease in systolic blood pressure, a 20 mm Hg decrease in diastolic blood pressure, and a 4 beat/min decrease in heart rate. Drowsiness was significantly increased and performance on the psychomotor task was significantly impaired. Fluvoxamine and tizanidine should not be used together [see Contraindications (4.1)].","","ncit:positive","ncit:quantitative",,"tizanidine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","4","Fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","SD","Oral","1","Daily","Oral","4","10","33","Fold","Increase","Unk","UNK","UNK","12","Fold","Increase","3","Fold","Increase" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/cc9e1c8c-0e2b-44e2-878b-27057f786be9.html","2015-08-20 13:57:35 -0400","drug-drug-interaction","evidence-supports"," Immune-Modulating Therapies ","Antineoplastic, immune-modulating, or immunosuppressive therapies, (including corticosteroids) are expected to increase the risk of immunosuppression, and the risk of additive immune system effects must be considered if these therapies are coadministered with GILENYA. When switching from drugs with prolonged immune effects, such as natalizumab, teriflunomide or mitoxantrone, the duration and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects when initiating GILENYA [see Warnings and Precautions (5.2)].","","ncit:positive","ncit:Qualitative",,"mitoxantrone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","GILENYA","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:42:22 -0400","drug-drug-interaction","evidence-supports","nical Pharmacology (12.3) ] . ","No dose adjustment of alprazolam, ibuprofen, levothyroxine, olanzapine, risperdione, warfarin, or strong CYP3A4 inhibitors (e.g., ketoconazole) is necessary when these drugs are used in combination with EMSAM. EMSAM had no clinically relevant effect on pharmacokinetics of these drugs.","","ncit:negative","ncit:Qualitative",,"levothyroxine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","EMSAM","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:38:35 -0500","DDI-clinical-trial","evidence-supports","","Lithium - Coadministration of Celexa (40 mg/day for 10 days) and lithium (30 mmol/day for 5 days) had no significant effect on the pharmacokinetics of citalopram or lithium. Nevertheless, plasma lithium levels should be monitored with appropriate adjustment to the lithium dose in accordance with standard clinical practice. Because lithium may enhance the serotonergic effects of citalopram, caution should be exercised when Celexa and lithium are coadministered.","","ncit:negative","ncit:quantitative",,"lithium","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","30 mmol","citalopram","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","40","Daily","Oral","10","Daily","IV","5","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/829a4f51-c882-4b64-81f3-abfb03a52ebe.html","2015-10-29 09:04:02 -0400","DDI-clinical-trial","evidence-supports"," 7.5 Lorazepam ","Under steady-state conditions for duloxetine (60 mg Q 12 hours) and lorazepam (2 mg Q 12 hours), the pharmacokinetics of duloxetine were not affected by co-administration. ","","ncit:negative","ncit:quantitative",,"lorazepam","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","2","duloxetine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","60","Q12",,"Unk","Q12","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","drug-drug-interaction","evidence-supports","see Drug Interactions (7) ] . ","Teriflunomide did not affect the pharmacokinetics of bupropion (a CYP2B6 substrate), midazolam (a CYP3A4 substrate), S-warfarin (a CYP2C9 substrate), omeprazole (a CYP2C19 substrate), and metoprolol (a CYP2D6 substrate).","","ncit:negative","ncit:Qualitative",,"Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","bupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","is a relatively weak inhibitor of CYP2D6. ","Approximately 7% of the normal population has a genetic code that leads to reduced levels of activity of CYP2D6. Such individuals have been referred to as “poor metabolizers” (PM) of drugs such as debrisoquin, dextromethorphan, and tricyclic antidepressants. While none of the drugs studied for drug interactions significantly affected the pharmacokinetics of fluvoxamine, an in vivo study of fluvoxamine single-dose pharmacokinetics in 13 PM subjects demonstrated altered pharmacokinetic properties compared to 16 “extensive metabolizers” (EM): mean Cmax, AUC, and half-life were increased by 52%, 200%, and 62%, respectively, in the PM compared to the EM group. This suggests that fluvoxamine is metabolized, at least in part, by CYP2D6. Caution is indicated in patients known to have reduced levels of CYP2D6 activity and those receiving concomitant drugs known to inhibit this cytochrome P450 isoenzyme (e.g., quinidine). ","","ncit:positive","ncit:Qualitative",,"fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"quinidine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c00d1607-ac36-457b-a34b-75ad74f9cf0a.html","2015-10-13 11:13:09 -0400","drug-drug-interaction","evidence-supports","ther Drugs to Affect INVIRASE ","The metabolism of saquinavir is mediated primarily by CYP3A. Additionally, saquinavir is a substrate for P-glycoprotein (P-gp). Therefore, drugs that affect CYP3A and/or P-gp may modify the pharmacokinetics of saquinavir. Coadministration with drugs that are potent inducers of CYP3A (e.g., phenobarbital, phenytoin, carbamazepine) may result in decreased plasma concentrations of saquinavir and reduced therapeutic effect.","","ncit:positive","ncit:Qualitative",,"phenobarbital","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","saquinavir","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b8881a81-75d7-43e8-825f-37c352c146dc.html","2015-11-04 14:19:06 -0500","drug-drug-interaction","evidence-supports","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquine hydroxylase) is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small or quite large (8 fold increase in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics, propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction",,"antidepressants","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","7.1 Potential Interactions with Drugs that Inhibit or are Metabolized by Cytochrome P450 Isoenzymes ","Multiple hepatic cytochrome P450 isoenzymes are involved in the oxidative biotransformation of a large number of structurally different drugs and endogenous compounds. The available knowledge concerning the relationship of fluvoxamine and the cytochrome P450 isoenzyme system has been obtained mostly from pharmacokinetic interaction studies conducted in healthy volunteers, but some preliminary in vitro data are also available. Based on a finding of substantial interactions of fluvoxamine with certain of these drugs [see later parts of this section and also Warnings and Precautions (5)] and limited in vitro data for CYP3A4, it appears that fluvoxamine inhibits several cytochrome P450 isoenzymes that are known to be involved in the metabolism of other drugs such as: CYP1A2 (e.g., warfarin, theophylline, propranolol, tizanidine), CYP2C9 (e.g., warfarin), CYP3A4 (e.g., alprazolam), and CYP2C19 (e.g., omeprazole). ","","ncit:positive","ncit:Qualitative",,"tizanidine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","DDI-clinical-trial","evidence-supports","(7) ] . Oral Contraceptives ","There was an increase in mean ethinylestradiol Cmax and AUC0–24 (1.58- and 1.54-fold, respectively) and levonorgestrel Cmax and AUC0–24 (1.33- and 1.41-fold, respectively) following repeated doses of teriflunomide [see Drug Interactions (7)].","","ncit:positive","ncit:quantitative",,"teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","levonorgestrel","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","1.41","Fold","Increase","Unk","UNK","UNK","1.33","Fold","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-09-14 11:21:10 -0400","DDI-clinical-trial","evidence-supports","","Concomitant use of paroxetine with risperidone, a CYP2D6 substrate has also been evaluated. In 1 study, daily dosing of paroxetine 20 mg in patients stabilized on risperidone (4 to 8 mg/day) increased mean plasma concentrations of risperidone approximately 4-fold, decreased 9-hydroxyrisperidone concentrations approximately 10%, and increased concentrations of the active moiety (the sum of risperidone plus 9-hydroxyrisperidone) approximately 1.4-fold."," The effect of","ncit:positive","ncit:quantitative",,"paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","risperidone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","4-8","Daily","Oral","Unk","Daily","Oral","Unk","Unk","4","Fold","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:13:01 -0400","DDI-clinical-trial","evidence-supports","","Ibuprofen In subjects who had received EMSAM 6 mg per 24 hours for 11 days, combined administration with the CYP2C9 substrate ibuprofen (800 mg single dose) did not affect the pharmacokinetics of either selegiline or ibuprofen [see Drug Interactions (7.4) and (7.5)]. ","","ncit:negative","ncit:quantitative",,"EMSAM","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","6","ibuprofen","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","800","SD","Oral","1","Daily","transdermal","11","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1809bcb4-5fcc-45ca-986a-4fa5edcd4b5e.html","2015-09-29 09:58:27 -0400","drug-drug-interaction","evidence-supports","er tricyclic antidepressants. ","The plasma concentration of CMI has been reported to be increased by the concomitant administration of haloperidol; plasma levels of several closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of methylphenidate or hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by the concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin), and such an effect may be anticipated with CMI as well. Administration of CMI has been reported to increase the plasma levels of phenobarbital, if given concomitantly (see CLINICAL PHARMACOLOGY, Interactions).","","ncit:positive","ncit:Qualitative",,"tricyclic antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","methylphenidate","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/cc9e1c8c-0e2b-44e2-878b-27057f786be9.html","2015-08-20 13:57:35 -0400","drug-drug-interaction","evidence-supports","beta blockers or diltiazem ) ","Experience with GILENYA in patients receiving concurrent therapy with drugs that slow the heart rate or atrioventricular conduction (e.g., beta blockers, digoxin, or heart rate-slowing calcium channel blockers such as diltiazem or verapamil) is limited. Because initiation of GILENYA treatment may result in an additional decrease in heart rate, concomitant use of these drugs during GILENYA initiation may be associated with severe bradycardia or heart block. Seek advice from the prescribing physician regarding the possibility to switch to drugs that do not slow the heart rate or atrioventricular conduction before initiating GILENYA. Patients who cannot switch, should have overnight continuous ECG monitoring after the first dose [see Dosage and Administration (2) and Warnings and Precautions (5.1)].","","ncit:positive","ncit:Qualitative",,"diltiazem","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","GILENYA","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:35:24 -0400","DDI-clinical-trial","evidence-supports"," Cimetidine ","In healthy male patients (n=12), when cimetidine, a weak inhibitor of CYP1A2, CYP2D6, and CYP3A4, given at 800 mg b.i.d. at steady state was coadministered with mirtazapine (30 mg daily) at steady state, the Area Under the Curve (AUC) of mirtazapine increased more than 50%. Mirtazapine did not cause relevant changes in the pharmacokinetics of cimetidine. The mirtazapine dose may have to be decreased when concomitant treatment with cimetidine is started, or increased when cimetidine treatment is discontinued.","","ncit:positive","ncit:quantitative",,"cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","800","mirtazapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","30","Daily","Oral","Unk","BID","Oral","Unk","12","50","Percent","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","SSRIs","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/3e593725-3fc9-458e-907d-19d51d5a7f9c.html","2015-09-29 11:28:40 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type IC antiarrhythmics propafenone and flecainide). While all the SSRIs, e.g., fluoxetine, sertraline, paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","SSRIs","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:30:38 -0500","DDI-clinical-trial","evidence-supports"," 7.13 Warfarin ","Administration of 40 mg/day racemic citalopram for 21 days did not affect the pharmacokinetics of warfarin, a CYP3A4 substrate. Prothrombin time was increased by 5%, the clinical significance of which is unknown. ","","ncit:negative","ncit:quantitative",,"citalopram","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","warfarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","Daily","Oral","21","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-10-28 15:25:57 -0400","DDI-clinical-trial","evidence-supports","","Many drugs, including most drugs effective in the treatment of major depressive disorder (paroxetine, other SSRIs and many tricyclics), are metabolized by the cytochrome P450 isozyme CYP2D6. Like other agents that are metabolized by CYP2D6, paroxetine may significantly inhibit the activity of this isozyme. In most patients (>90%), this CYP2D6 isozyme is saturated early during dosing with paroxetine. In 1 study, daily dosing of paroxetine (20 mg once daily) under steady-state conditions increased single dose desipramine (100 mg) Cmax, AUC, and T½ by an average of approximately 2-, 5-, and 3-fold, respectively. ","Concomitant use of","ncit:positive","ncit:quantitative",,"paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","desipramine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","100","SD","Oral","Unk","Daily","Oral","Unk","Unk","5","Fold","Increase","Unk","UNK","UNK","2","Fold","Increase","3","Fold","Increase" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e338e89-3cf2-48eb-b6e2-a06c608c6513.html","2015-08-20 11:32:27 -0400","drug-drug-interaction","evidence-supports","e Drug Interactions (7.1) ] . ","In a separate clinical pharmacokinetic interaction study of healthy subjects, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone [see Drug Interactions (7.1)].","","ncit:negative","ncit:Qualitative",,"abiraterone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","ketoconazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-09-03 15:42:22 -0400","drug-drug-interaction","evidence-supports","nical Pharmacology (12.3) ] . ","No dose adjustment of alprazolam, ibuprofen, levothyroxine, olanzapine, risperdione, warfarin, or strong CYP3A4 inhibitors (e.g., ketoconazole) is necessary when these drugs are used in combination with EMSAM. EMSAM had no clinically relevant effect on pharmacokinetics of these drugs. ","","ncit:negative","ncit:Qualitative",,"EMSAM","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","","alprazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/829a4f51-c882-4b64-81f3-abfb03a52ebe.html","2015-10-29 09:10:04 -0400","DDI-clinical-trial","evidence-supports"," Drugs Metabolized by CYP1A2 ","In vitro drug interaction studies demonstrate that duloxetine does not induce CYP1A2 activity. Therefore, an increase in the metabolism of CYP1A2 substrates (e.g., theophylline, caffeine) resulting from induction is not anticipated, although clinical studies of induction have not been performed. Duloxetine is an inhibitor of the CYP1A2 isoform in in vitro studies, and in two clinical studies the average (90% confidence interval) increase in theophylline AUC was 7% (1% to 15%) and 20% (13% to 27%) when co-administered with duloxetine (60 mg twice daily). ","","ncit:positive","ncit:quantitative",,"theophylline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","duloxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","60","UNK","UNK","Unk","BID","Oral","Unk","Unk","7-20","Percent","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:13:14 -0500","DDI-clinical-trial","evidence-supports","erythrohydrobupropion decreased by 68%. ","In another healthy volunteer study, lopinavir 400 mg/ritonavir 100 mg twice daily decreased bupropion AUC and Cmax by 57%. The AUC and Cmax of hydroxybupropion metabolite were decreased by 50% and 31%, respectively.","","ncit:positive","ncit:quantitative",,"hydroxybupropion","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","lopinavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","400","UNK","UNK","Unk","BID","Oral","Unk","Unk","50","Percent","Decrease","Unk","UNK","UNK","31","Percent","Decrease","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e17dc299-f52d-414d-ab6e-e809bd6f8acb.html","2015-11-04 14:14:49 -0500","drug-drug-interaction","evidence-supports","(TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"propafenone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/e17dc299-f52d-414d-ab6e-e809bd6f8acb.html","2015-11-04 14:14:49 -0500","drug-drug-interaction","evidence-supports","(TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","phenothiazines","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:38:04 -0400","drug-drug-interaction","evidence-supports"," Carbamazepine ","Elevated carbamazepine levels and symptoms of toxicity have been reported with the coadministration of fluvoxamine maleate and carbamazepine. ","","ncit:positive","ncit:Qualitative",,"carbamazepine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine maleate","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 14:27:00 -0400","drug-drug-interaction","evidence-supports"," Benzodiazepines ","Benzodiazepines metabolized by hepatic oxidation (e.g., alprazolam, midazolam, triazolam, etc.) should be used with caution because the clearance of these drugs is likely to be reduced by fluvoxamine.","","ncit:positive","ncit:Qualitative",,"midazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 13:32:33 -0500","DDI-clinical-trial","evidence-supports","","Digoxin - In subjects who had received 21 days of 40 mg/day Celexa, combined administration of Celexa and digoxin (single dose of 1 mg) did not significantly affect the pharmacokinetics of either citalopram or digoxin.","","ncit:negative","ncit:quantitative",,"citalopram","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","digoxin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","1","SD","Oral","1","Daily","Oral","21","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e338e89-3cf2-48eb-b6e2-a06c608c6513.html","2015-08-20 11:10:08 -0400","DDI-clinical-trial","evidence-supports"," on Drug Metabolizing Enzymes ","ZYTIGA is an inhibitor of the hepatic drug-metabolizing enzymes CYP2D6 and CYP2C8. In a CYP2D6 drug-drug interaction trial, the Cmax and AUC of dextromethorphan (CYP2D6 substrate) were increased 2.8- and 2.9-fold, respectively, when dextromethorphan was given with abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily. Avoid co-administration of abiraterone acetate with substrates of CYP2D6 with a narrow therapeutic index (e.g., thioridazine). If alternative treatments cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate drug [see Clinical Pharmacology (12.3)].","","ncit:positive","ncit:quantitative",,"abiraterone acetate","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","dextromethorphan","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","1000","UNK","UNK","Unk","Daily","UNK","Unk","Unk","2.9","Fold","Increase","Unk","UNK","UNK","2.8","Fold","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b891bd9f-fdb8-4862-89c5-ecdd700398a3.html","2015-10-27 14:13:55 -0400","DDI-clinical-trial","evidence-supports","","Levothyroxine In healthy subjects who had received EMSAM 6 mg per 24 hours for 10 days, single dose administration with levothyroxine (150 mcg) did not alter the pharmacokinetics of either selegiline or levothyroxine [see Drug Interactions (7.4) and (7.5)].","","ncit:negative","ncit:quantitative",,"EMSAM","dikbD2R:drug-product","dikbD2R:object-drug-of-interaction","6","levothyroxine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","0.15","Daily","transdermal","10","SD","Oral","1","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/75bf3473-2d70-4d41-93cd-afa1015e45bb.html","2015-10-01 10:49:57 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","propafenone","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/cc9e1c8c-0e2b-44e2-878b-27057f786be9.html","2015-08-20 13:57:35 -0400","drug-drug-interaction","evidence-supports","beta blockers or diltiazem ) ","Experience with GILENYA in patients receiving concurrent therapy with drugs that slow the heart rate or atrioventricular conduction (e.g., beta blockers, digoxin, or heart rate-slowing calcium channel blockers such as diltiazem or verapamil) is limited. Because initiation of GILENYA treatment may result in an additional decrease in heart rate, concomitant use of these drugs during GILENYA initiation may be associated with severe bradycardia or heart block. Seek advice from the prescribing physician regarding the possibility to switch to drugs that do not slow the heart rate or atrioventricular conduction before initiating GILENYA. Patients who cannot switch, should have overnight continuous ECG monitoring after the first dose [see Dosage and Administration (2) and Warnings and Precautions (5.1)].","","ncit:positive","ncit:Qualitative",,"GILENYA","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","","verapamil","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1809bcb4-5fcc-45ca-986a-4fa5edcd4b5e.html","2015-09-29 11:41:50 -0400","drug-drug-interaction","evidence-supports","er tricyclic antidepressants. ","The plasma concentration of CMI has been reported to be increased by the concomitant administration of haloperidol; plasma levels of several closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of methylphenidate or hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by the concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin), and such an effect may be anticipated with CMI as well. Administration of CMI has been reported to increase the plasma levels of phenobarbital, if given concomitantly (see CLINICAL PHARMACOLOGY, Interactions).","","ncit:positive","ncit:Qualitative",,"tricyclic antidepressants","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","CMI","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:48:13 -0500","DDI-clinical-trial","evidence-supports"," 7.20 Metoprolol ","Administration of 20 mg/day Lexapro for 21 days in healthy volunteers resulted in a 50% increase in Cmax and 82% increase in AUC of the beta-adrenergic blocker metoprolol (given in a single dose of 100 mg). Increased metoprolol plasma levels have been associated with decreased cardioselectivity. Coadministration of Lexapro and metoprolol had no clinically significant effects on blood pressure or heart rate. ","","ncit:positive","ncit:quantitative",,"metoprolol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","100","Lexapro","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","20","SD","Oral","1","Daily","Oral","21","Unk","82","Percent","Increase","Unk","UNK","UNK","50","Percent","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/b8881a81-75d7-43e8-825f-37c352c146dc.html","2015-11-04 14:21:12 -0500","drug-drug-interaction","evidence-supports","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquine hydroxylase) is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small or quite large (8 fold increase in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics, propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:36:27 -0400","DDI-clinical-trial","evidence-supports","apy is initiated or stopped. ","Cimetidine–In a study assessing disposition of sertraline (100 mg) on the second of 8 days of cimetidine administration (800 mg daily), there were significant increases in sertraline mean AUC (50%), Cmax (24%) and half-life (26%) compared to the placebo group. The clinical significance of these changes is unknown.","","ncit:positive","ncit:quantitative",,"sertraline","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","100","cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","800","SD","Oral","1","Daily","Oral","8","Unk","50","Percent","Increase","Unk","UNK","UNK","24","Percent","Increase","26","Percent","Increase" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c66a11c1-3093-45ef-b348-3b196c05ba0c.html","2015-10-01 10:31:02 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dosage regimen of a TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"phenothiazines","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction","","TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f356c1b-96bd-4ef1-960c-91cf4905e6b1.html","2015-11-03 12:56:19 -0500","DDI-clinical-trial","evidence-supports","","Tricyclic Antidepressants (TCAs) — In 2 studies, previously stable plasma levels of imipramine and desipramine have increased greater than 2- to 10-fold when fluoxetine has been administered in combination. This influence may persist for 3 weeks or longer after fluoxetine is discontinued. Thus, the dose of TCAs may need to be reduced and plasma TCA concentrations may need to be monitored temporarily when fluoxetine is coadministered or has been recently discontinued [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)]. ","","ncit:positive","ncit:quantitative",,"desipramine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","2 to 10","Fold","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 15:49:45 -0500","DDI-clinical-trial","evidence-supports",", respectively. The exposures of hydroxybupropion were decreased. ","Prasugrel: In healthy subjects, prasugrel increased bupropion Cmax and AUC values by 14% and 18%, respectively, and decreased Cmax and AUC values of hydroxybupropion by 32% and 24%, respectively.","","ncit:positive","ncit:quantitative",,"prasugrel","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","hydroxybupropion","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","24","Percent","Decrease","Unk","UNK","UNK","32","Percent","Decrease","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 13:06:41 -0400","DDI-clinical-trial","evidence-supports","er Drugs CYP2C8 Substrates ","There was an increase in mean repaglinide Cmax and AUC (1.7- and 2.4-fold, respectively), following repeated doses of teriflunomide and a single dose of 0.25 mg repaglinide, suggesting that teriflunomide is an inhibitor of CYP2C8 in vivo. The magnitude of interaction could be higher at the recommended repaglinide dose [see Drug Interactions (7)].","","ncit:positive","ncit:quantitative",,"repaglinide","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","0.25","SD","UNK","1","UNK","UNK","Unk","Unk","2.4","Fold","Increase","Unk","UNK","UNK","1.7","Fold","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5d103551-978f-472a-9c62-51e6e4dea068.html","2015-10-09 13:39:25 -0400","DDI-clinical-trial","evidence-supports","uring treatment with ACIPHEX. ","Concomitant treatment with rabeprazole (20 mg daily) and ketoconazole in healthy subjects decreased the bioavailability of ketoconazole by 30% and increased the AUC and Cmax for digoxin by 19% and 29%, respectively. Therefore, patients may need to be monitored when such drugs are taken concomitantly with rabeprazole. Co-administration of rabeprazole and antacids produced no clinically relevant changes in plasma rabeprazole concentrations.","","ncit:positive","ncit:quantitative",,"ketoconazole","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","rabeprazole","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","20","UNK","UNK","Unk","Daily","Oral","Unk","Unk","19","Percent","Increase","Unk","UNK","UNK","29","Percent","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4650d12c-b9c8-4525-b07f-a2d773eca155.html","2015-08-20 12:50:04 -0400","drug-drug-interaction","evidence-supports"," B3 (OATP1B1/1B3) substrates ","Teriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo. For a patient taking AUBAGIO, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking AUBAGIO [see Clinical Pharmacology (12.3)]","","ncit:positive","ncit:Qualitative",,"Teriflunomide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","pravastatin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a16297df-3158-48db-85e5-5cd506885556.html","2015-09-29 09:27:10 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine, cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"flecainide","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a16297df-3158-48db-85e5-5cd506885556.html","2015-09-29 09:27:10 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine, cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","phenothiazines","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:48:41 -0400","DDI-clinical-trial","evidence-supports"," Risperidone ","In an in vivo, nonrandomized, interaction study, subjects (n=6) in need of treatment with an antipsychotic and antidepressant drug, showed that mirtazapine (30 mg daily) at steady state did not influence the pharmacokinetics of risperidone (up to 3 mg b.i.d.).","","ncit:negative","ncit:quantitative",,"risperidone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","3","mirtazapine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","30","BID","Oral","Unk","Daily","Oral","Unk","6","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/5f356c1b-96bd-4ef1-960c-91cf4905e6b1.html","2015-09-10 14:36:47 -0400","drug-drug-interaction","evidence-supports","","Benzodiazepines — The half-life of concurrently administered diazepam may be prolonged in some patients [see Clinical Pharmacology (12.3)]. Coadministration of alprazolam and fluoxetine has resulted in increased alprazolam plasma concentrations and in further psychomotor performance decrement due to increased alprazolam levels. ","","ncit:positive","ncit:Qualitative",,"fluoxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","","alprazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c66a11c1-3093-45ef-b348-3b196c05ba0c.html","2015-10-29 11:36:33 -0400","drug-drug-interaction","evidence-supports","se in plasma AUC of the TCA). ","In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dosage regimen of a TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).","","ncit:positive","ncit:Qualitative",,"TCA","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction",,"cimetidine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/1809bcb4-5fcc-45ca-986a-4fa5edcd4b5e.html","2015-09-29 09:58:27 -0400","drug-drug-interaction","evidence-supports","er tricyclic antidepressants. ","The plasma concentration of CMI has been reported to be increased by the concomitant administration of haloperidol; plasma levels of several closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of methylphenidate or hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by the concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin), and such an effect may be anticipated with CMI as well. Administration of CMI has been reported to increase the plasma levels of phenobarbital, if given concomitantly (see CLINICAL PHARMACOLOGY, Interactions).","","ncit:positive","ncit:Qualitative",,"tricyclic antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","","hepatic enzyme inhibitors","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction","","","","","","","","","","","","","","","","","","","","" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-09-14 11:31:14 -0400","DDI-clinical-trial","evidence-supports"," not evaluated. Procyclidine ","Daily oral dosing of paroxetine (30 mg once daily) increased steady-state AUC0-24, Cmax, and Cmin values of procyclidine (5 mg oral once daily) by 35%, 37%, and 67%, respectively, compared to procyclidine alone at steady state. If anticholinergic effects are seen, the dose of procyclidine should be reduced.","","ncit:positive","ncit:quantitative",,"paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","30","procyclidine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","5","Daily","Oral","Unk","Daily","Oral","Unk","Unk","35","Percent","Increase","Unk","UNK","UNK","37","Percent","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/c25f968b-7037-4f60-9a02-2189769b0cbf.html","2015-10-28 16:37:51 -0400","drug-drug-interaction","evidence-supports","max were reduced by about 35%). ","Drugs Metabolized by P450 2D6–Many drugs effective in the treatment of major depressive disorder, e.g., the SSRIs, including sertraline, and most tricyclic antidepressant drugs effective in the treatment of major depressive disorder inhibit the biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase), and, thus, may increase the plasma concentrations of co-administered drugs that are metabolized by P450 2D6. The drugs for which this potential interaction is of greatest concern are those metabolized primarily by 2D6 and which have a narrow therapeutic index, e.g., the tricyclic antidepressant drugs effective in the treatment of major depressive disorder and the Type 1C antiarrhythmics propafenone and flecainide. The extent to which this interaction is an important clinical problem depends on the extent of the inhibition of P450 2D6 by the antidepressant and the therapeutic index of the co-administered drug. There is variability among the drugs effective in the treatment of major depressive disorder in the extent of clinically important 2D6 inhibition, and in fact sertraline at lower doses has a less prominent inhibitory effect on 2D6 than some others in the class. Nevertheless, even sertraline has the potential for clinically important 2D6 inhibition. Consequently, concomitant use of a drug metabolized by P450 2D6 with sertraline may require lower doses than usually prescribed for the other drug. Furthermore, whenever sertraline is withdrawn from co-therapy, an increased dose of the co-administered drug may be required (see Tricyclic Antidepressant Drugs Effective in the Treatment of Major Depressive Disorder under PRECAUTIONS).","","ncit:positive","ncit:Qualitative",,"propafenone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","","sertraline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:07:34 -0500","DDI-clinical-trial","evidence-supports","decreased by 48%. ","In a second healthy volunteer study, ritonavir 600 mg twice daily decreased the AUC and Cmax of bupropion by 66% and 62% respectively. The exposure of the hydroxybupropion metabolite was decreased by 78%, the threohydrobupropion decreased by 50%, and the erythrohydrobupropion decreased by 68%. ","","ncit:positive","ncit:quantitative","Exposure decreased by 78%","ritonavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","hydroxybupropion","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","BID","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/326e8ab0-6886-4749-9544-885b37070051.html","2015-10-28 14:38:28 -0400","DDI-clinical-trial","evidence-supports","Thioridazine administration alone produces prolongation of the QTc interval, which is associated with serious ventricular arrhythmias, such as torsade de pointes–type arrhythmias, and sudden death. This effect appears to be dose related.  ","An in vivo study suggests that drugs which inhibit CYP2D6, such as paroxetine, will elevate plasma levels of thioridazine. Therefore, it is recommended that paroxetine not be used in combination with thioridazine (see CONTRAINDICATIONS and PRECAUTIONS). ","","ncit:positive","ncit:quantitative",,"thioridazine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","paroxetine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:05:45 -0500","DDI-clinical-trial","evidence-supports","Inducers of CYP2B6 Ritonavir and Lopinavir : ","In a healthy volunteer study, ritonavir 100 mg twice daily reduced the AUC and Cmax of bupropion by 22% and 21%, respectively. The exposure of the hydroxybupropion metabolite was decreased by 23%, the threohydrobupropion decreased by 38%, and the erythrohydrobupropion decreased by 48%. ","","ncit:positive","ncit:quantitative","Exposure decreased by 38%","ritonavir","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","threohydrobupropion","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","Unk","UNK","UNK","Unk","BID","Oral","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/f371258d-91b3-4b6a-ac99-434a1964c3af.html","2015-10-29 09:45:11 -0400","drug-drug-interaction","evidence-supports"," is not an inhibitor of CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, P-gp, OATP1B1, OATP1B3, OAT1, OAT3, or OCT2. ","Concomitant use of FETZIMA with alprazolam or carbamazepine, substrates of CYP3A4, had no significant effect on alprazolam or carbamazepine plasma concentrations ","(see","ncit:negative","ncit:Qualitative",,"FETZIMA","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction",,"alprazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 14:27:00 -0400","drug-drug-interaction","evidence-supports",", etc.) should be used with caution because the clearance of these drugs is likely to be reduced by fluvoxamine . ","The clearance of benzodiazepines metabolized by glucuronidation (e.g., lorazepam, oxazepam, temazepam) is unlikely to be affected by fluvoxamine. ","","ncit:negative","ncit:Qualitative",,"fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"lorazepam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4e338e89-3cf2-48eb-b6e2-a06c608c6513.html","2015-08-20 11:32:27 -0400","DDI-clinical-trial","evidence-supports","e Drug Interactions (7.1) ] . ","In a CYP2C8 drug-drug interaction trial in healthy subjects, the AUC of pioglitazone was increased by 46% when pioglitazone was given together with a single dose of 1,000 mg abiraterone acetate [see Drug Interactions (7.2)].","","ncit:positive","ncit:quantitative",,"pioglitazone","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","1000","abiraterone acetate","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","SD","UNK","1","Unk","46","Percent","Increase","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:32:17 -0500","DDI-clinical-trial","evidence-supports"," 7.14 Carbamazepine ","Combined administration of racemic citalopram (40 mg/day for 14 days) and carbamazepine (titrated to 400 mg/day for 35 days) did not significantly affect the pharmacokinetics of carbamazepine, a CYP3A4 substrate. Although trough citalopram plasma levels were unaffected, given the enzyme-inducing properties of carbamazepine, the possibility that carbamazepine might increase the clearance of escitalopram should be considered if the two drugs are coadministered. ","","ncit:negative","ncit:quantitative",,"citalopram","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","carbamazepine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","400","Daily","Oral","35","Daily","Oral","14","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/0177d783-773c-41bf-9db9-eb7e5c64474a.html","2015-11-05 10:40:12 -0500","drug-drug-interaction","evidence-supports","Drugs Metabolized by P450 2D6 ","The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7-10% of caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of the isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.","","ncit:positive","ncit:Qualitative",,"phenothiazines","dikbD2R:drug-group","dikbD2R:precipitant-drug-of-interaction",,"tricyclic antidepressants","dikbD2R:drug-group","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","DDI-clinical-trial","evidence-supports"," Lorazepam ","A study of multiple doses of fluvoxamine maleate (50 mg b.i.d.) in healthy male volunteers (N = 12) and a single dose of lorazepam (4 mg single dose) indicated no significant pharmacokinetic interaction. On average, both lorazepam alone and lorazepam with fluvoxamine produced substantial decrements in cognitive functioning; however, the coadministration of fluvoxamine and lorazepam did not produce larger mean decrements compared to lorazepam alone. ","","ncit:negative","ncit:quantitative",,"lorazepam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","4","fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","50","SD","Oral","1","BID","Oral","Unk","12","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/829a4f51-c882-4b64-81f3-abfb03a52ebe.html","2015-10-29 08:58:27 -0400","DDI-clinical-trial","evidence-supports"," 7.1 Inhibitors of CYP1A2 ","When duloxetine 60 mg was co-administered with fluvoxamine 100 mg, a potent CYP1A2 inhibitor, to male subjects (n=14) duloxetine AUC was increased approximately 6-fold, the Cmax was increased about 2.5-fold, and duloxetine t1/2 was increased approximately 3-fold. Other drugs that inhibit CYP1A2 metabolism include cimetidine and quinolone antimicrobials such as ciprofloxacin and enoxacin [see WARNINGS AND PRECAUTIONS (5.12)]. ","","ncit:positive","ncit:quantitative",,"fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","100","duloxetine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","60","UNK","Oral","Unk","UNK","Oral","Unk","14","6","Fold","Increase","Unk","UNK","UNK","2.5","Fold","Increase","3","Fold","Increase" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/a435da9d-f6e8-4ddc-897d-8cd2bf777b21.html","2015-11-05 16:15:31 -0500","DDI-clinical-trial","evidence-supports","metabolite were decreased by 50% and 31%, respectively. ","Efavirenz: In a study of healthy volunteers, efavirenz 600 mg once daily for 2 weeks reduced the AUC and Cmax of bupropion by approximately 55% and 34%, respectively. The AUC of hydroxybupropion was unchanged, whereas Cmax of hydroxybupropion was increased by 50%.","","ncit:positive","ncit:quantitative",,"hydroxybupropion","dikbD2R:metabolite","dikbD2R:object-drug-of-interaction","Unk","efavirenz","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","600","UNK","UNK","Unk","Daily","Oral","14","Unk","Unk","UNK","UNK","Unk","UNK","UNK","50","Percent","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/53664f8d-3a93-9f2b-daee-380707e4062c.html","2015-10-27 15:37:39 -0400","drug-drug-interaction","evidence-supports","metabolism have not been studied. ","A clinically significant fluvoxamine interaction is possible with drugs having a narrow therapeutic ratio such as pimozide, warfarin, theophylline, certain benzodiazepines, omeprazole and phenytoin. If fluvoxamine maleate tablets are to be administered together with a drug that is eliminated via oxidative metabolism and has a narrow therapeutic window, plasma levels and/or pharmacodynamic effects of the latter drug should be monitored closely, at least until steady-state conditions are reached [see Contraindications (4) and Warnings and Precautions (5)]. ","","ncit:positive","ncit:Qualitative",,"fluvoxamine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction",,"warfarin","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","",,,,,,,,,,,,,,,,,,, +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/4259d9b1-de34-43a4-85a8-41dd214e9177.html","2015-11-02 14:00:44 -0500","DDI-clinical-trial","evidence-supports"," AND CLINICAL PHARMACOLOGY ). ","Metoprolol - Administration of 40 mg/day Celexa for 22 days resulted in a two-fold increase in the plasma levels of the beta-adrenergic blocker metoprolol. Increased metoprolol plasma levels have been associated with decreased cardioselectivity. Coadministration of Celexa and metoprolol had no clinically significant effects on blood pressure or heart rate.","","ncit:positive","ncit:quantitative",,"metoprolol","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","Celexa","dikbD2R:drug-product","dikbD2R:precipitant-drug-of-interaction","40","UNK","UNK","Unk","Daily","Oral","22","Unk","Unk","UNK","UNK","Unk","UNK","UNK","2","Fold","Increase","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/f371258d-91b3-4b6a-ac99-434a1964c3af.html","2015-10-29 09:45:10 -0400","DDI-clinical-trial","evidence-supports","ketoconazole (see Figure 1 ). ","No dose adjustment of FETZIMA is needed when co-administered with a CYP3A4 inducer or substrate. In vivo studies showed no clinically meaningful change in levomilnacipran exposure when co-administered with the CYP3A4 inducer carbamazepine or the CYP3A4 substrate alprazolam (see Figure 1). ","","ncit:negative","ncit:quantitative",,"levomilnacipran","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","Unk","carbamazepine","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","Unk","UNK","UNK","Unk","UNK","UNK","Unk","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/010f9162-9f7f-4b6d-a6e4-4f832f26f38e.html","2015-10-29 10:48:14 -0400","DDI-clinical-trial","evidence-supports"," Amitriptyline ","In healthy, CYP2D6 extensive metabolizer patients (n=32), amitriptyline (75 mg daily), at steady state, did not cause relevant changes in the pharmacokinetics of steady state mirtazapine (30 mg daily); mirtazapine also did not cause relevant changes to the pharmacokinetics of amitriptyline.","","ncit:negative","ncit:quantitative",,"amitriptyline","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","75","mirtazapine","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","30","Daily","Oral","Unk","Daily","Oral","Unk","32","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" +"http://dbmi-icode-01.dbmi.pitt.edu:80/DDI-labels/13bb8267-1cab-43e5-acae-55a4d957630a.html","2015-11-02 14:33:30 -0500","DDI-clinical-trial","evidence-supports"," 7.15 Triazolam ","Combined administration of racemic citalopram (titrated to 40 mg/day for 28 days) and the CYP3A4 substrate triazolam (single dose of 0.25 mg) did not significantly affect the pharmacokinetics of either citalopram or triazolam. ","","ncit:negative","ncit:quantitative",,"citalopram","dikbD2R:active-ingredient","dikbD2R:precipitant-drug-of-interaction","40","triazolam","dikbD2R:active-ingredient","dikbD2R:object-drug-of-interaction","0.25","SD","Oral","1","Daily","Oral","28","Unk","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK","Unk","UNK","UNK" diff --git a/translation/RDB_ETL/preprocess.py b/translation/RDB_ETL/preprocess.py index 7982bff..c816b2b 100644 --- a/translation/RDB_ETL/preprocess.py +++ b/translation/RDB_ETL/preprocess.py @@ -3,9 +3,10 @@ import uuid import datetime -#1. add psycopg2 module +#1. pip install psycopg2 #2. config -csvfiles = ['pkddi-katrina-latest-08142016.csv', 'pkddi-amy-latest-08152016.csv'] + +csvfiles = ['pkddi-katrina-latest-08152016.csv', 'pkddi-amy-latest-08152016.csv'] hostname = 'localhost' username = 'username' password = 'password' @@ -14,10 +15,11 @@ def main(): - print("Using psycopg2") + print("insert data ...") myConnection = psycopg2.connect(host=hostname, user=username, password=password, dbname=database) - clearall(myConnection) - myConnection.commit() + #delete all data in table + #clearall(myConnection) + #myConnection.commit() for csvfile in csvfiles: preprocess(csvfile) @@ -95,12 +97,20 @@ def load_method(conn, row, mp_claim_id): def load_oa_selector(conn, row): cur = conn.cursor() urn = uuid.uuid4().hex + if row['prefix'] == '': + prefix = 'NULL' + else: + prefix = "'" + row['prefix'] + "'" + if row['suffix'] == '': + suffix = 'NULL' + else: + suffix = "'" + row['suffix'] + "'" cur.execute("INSERT INTO oa_selector (urn, selector_type, exact, prefix, suffix)" + - "VALUES ( '" + urn + "', 'oa_selector', '" + str(row['exactText']) + "', NULL, NULL);") + "VALUES ( '" + urn + "', 'oa_selector', '" + row['exactText'] + "', " + prefix + ", " + suffix + ");") cur.execute("SELECT * FROM oa_selector WHERE urn = '" + urn + "';") for urn in cur.fetchall(): - print(urn) + #print(urn) tempid = urn[0] return tempid @@ -114,7 +124,7 @@ def load_oa_target(conn, row, has_selector): cur.execute("SELECT * FROM oa_target WHERE urn = '" + urn + "';") for urn in cur.fetchall(): - print(urn) + #print(urn) tempid = urn[0] return tempid @@ -129,7 +139,7 @@ def load_oa_claim_body(conn, row): cur.execute("SELECT * FROM oa_claim_body WHERE urn = '" + urn + "';") for urn in cur.fetchall(): - print(urn) + #print(urn) tempid = urn[0] return tempid @@ -159,7 +169,7 @@ def load_mp_claim_annotation(conn, row, has_body, has_target, creator): cur.execute("SELECT * FROM mp_claim_annotation WHERE urn = '" + urn + "';") for urn in cur.fetchall(): - print(urn) + #print(urn) tempid = urn[0] return tempid @@ -237,11 +247,6 @@ def load_mp_material_annotation(conn, row, mp_claim_id, has_target, creator): material_body_id = helper_load_material(conn, row, mp_claim_id, has_target, creator, 'participants') load_material_field(conn, row, material_body_id, 'participants') - cur.execute("SELECT * FROM mp_material_annotation WHERE mp_claim_id = " + str(mp_claim_id) + ";") - - for urn in cur.fetchall(): - print(urn) - def helper_load_material(conn, row, mp_claim_id, has_target, creator, data_type): ev_supports = 'false' @@ -302,31 +307,31 @@ def parse_date(csv_date): # add column: predicate, subject, object, subjectDose, objectDose def preprocess(csvfile): - writer = csv.writer(open('preProcess.csv', 'w'), lineterminator='\n') - reader = csv.reader( - open(csvfile, 'r')) + csv_columns = ['source', 'date', 'assertionType', 'evidenceType', 'prefix', 'exactText', 'suffix', + 'modality', 'statementType', 'comment', 'drug1Lab', 'drug1Type', 'drug1Role', 'dose1', + 'drug2Lab', 'drug2Type', 'drug2Role', 'dose2', 'objectRegimens', 'objectFormulation', + 'objectDuration', 'preciptRegimens', 'preciptFormulation', 'preciptDuration', + 'numOfParticipants', 'auc', 'aucType', 'aucDirection', 'cl', 'clType', 'clDirection', + 'cmax', 'cmaxType', 'cmaxDirection', 't12', 't12Type', 't12Direction', 'predicate', + 'subject', 'object', 'subjectDose', 'objectDose'] + writer = csv.DictWriter(open('preProcess.csv', 'w'), fieldnames=csv_columns) + writer.writeheader() + reader = csv.DictReader(open(csvfile, 'r')) all = [] - row = next(reader) - row.append('predicate') - row.append('subject') - row.append('object') - row.append('subjectDose') - row.append('objectDose') - all.append(row) for row in reader: - row.append('interact_with') - if 'object' in row[10]: - row.append(row[12]) - row.append(row[8]) - row.append(row[15]) - row.append(row[11]) + #print(row) + + row.update({'predicate': 'interact_with'}) + if 'object' in row['drug1Role']: + row.update({'subject': row['drug2Lab'], 'object': row['drug1Lab'], 'subjectDose': row['dose2'], 'objectDose': row['dose1']}) else: - row.append(row[8]) - row.append(row[12]) - row.append(row[11]) - row.append(row[15]) - if "'" in row[4]: - row[4] = row[4].replace("'", "''") + row.update({'subject': row['drug1Lab'], 'object': row['drug2Lab'], 'subjectDose': row['dose1'], 'objectDose': row['dose2']}) + if "'" in row['prefix']: + row['prefix'] = row['prefix'].replace("'", "''") + if "'" in row['exactText']: + row['exactText'] = row['exactText'].replace("'", "''") + if "'" in row['suffix']: + row['suffix'] = row['suffix'].replace("'", "''") all.append(row) writer.writerows(all) diff --git a/translation/README b/translation/README new file mode 100644 index 0000000..97df699 --- /dev/null +++ b/translation/README @@ -0,0 +1,33 @@ +-------------------------------------------------------------------- +build database : running DDL +-------------------------------------------------------------------- + +mp_evidence/mp_evidence_schema_08202016.sql + +-------------------------------------------------------------------- +insert data : running DML +-------------------------------------------------------------------- + +1. cd RDB_ETL/ + +2. pip install psycopg2 + +3. configure data in preProcess.py +“ +csvfiles = ['pkddi-katrina-latest-08152016.csv', 'pkddi-amy-latest-08152016.csv'] +hostname = 'localhost' +username = 'username' +password = 'password' +database = 'mpevidence' +“ + +4. python preProcess.py + +-------------------------------------------------------------------- +* content in preProcess.py +-------------------------------------------------------------------- +1. preprocess csv, generate preProcess.csv +2. insert data into every table +3. delete all data in table + +