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Simvastatin co‐prescribed with protease inhibitors despite dangerous drug interactions

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Katherine M Coyne, Marta Boffito, Nick Theobald, and David Asboe +
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Author information ► Article notes ► Copyright and License information ►
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Drug interactions with anti‐retrovirals are frequent and can be dangerous. Protease inhibitors (PIs) inhibit the metabolism of simvastatin, and co‐administration is contraindicated. Despite this, we have seen a recent cluster of patients prescribed simvastatin whilst on PIs.

A 58‐year‐old man was taking abacavir, lamivudine, atazanavir and ritonavir. His HIV physician noted raised cholesterol and wrote to the patient and his general practitioner (GP), stating that simvastatin is not recommended with his antiretroviral combination, but low dose atorvastatin or pravastatin is safe. Simvastatin was prescribed by the GP.

A 52‐year‐old woman was taking didanosine, efavirenz, atazanavir and ritonavir, as well as gliclazide, doxazosin and bendrofluazide. A letter from her HIV physician to her GP listed her medications and mentioned that her cholesterol was 8.5. Her GP started simvastatin. The patient took the first dose but stopped after reading the medication insert leaflet.

A 53‐year‐old man was taking stavudine, lamivudine and nelfinavir. Pravastatin was started by his HIV physician, and letters were written regularly to his GP about current medications. Pravastatin was changed to simvastatin by his GP 6 years later.

At least four other patients at our centre on protease inhibitors (PIs) have recently been switched to simvastatin by GPs. None have suffered adverse consequences, although similar cases have resulted in rhabdomyolysis and death.

PIs, including ritonavir, atazanavir, lopinavir, saquinavir and nelfinavir, inhibit cytochrome P450 (CYP) 3A4 activity, which metabolises simvastatin and atorvastatin. Simvastatin exposure is increased by up to 3000% by PIs, and co‐administration is contraindicated. Atorvastatin concentrations are increased by a much smaller margin, and atorvastatin may be used cautiously. Pravastatin and rosuvastatin are not metabolised by CYP3A4 and are safe to use with PIs.

It should also be noted that efavirenz, a non‐nucleoside reverse transcriptase inhibitor, is an inducer of CYP3A4 metabolism, and reduces the concentrations of active simvastatin, atorvastatin and pravastatin by 58%, 34% and 40%, respectively.

GPs, and all physicians, are under pressure to prescribe cheaper medications where possible, and this is driving the switch to simvastatin. Simvastatin is also available without prescription in pharmacies. These cases highlight the importance of effective communication between HIV physicians, GPs and the patient, not only about current medications but also about potential drug interactions. Where PIs are being used, simvastatin must be avoided.

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Footnotes

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Competing interests: None.

Informed consent was obtained for publication of the patients' details in this report.

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References

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1. Hare C B, Vu M P, Grunfeld C. et al Simvastatin‐nelfinavir interaction implicated in rhabdomyolysis and death. Clin Infect Dis 200235e111–e112.e112 [PubMed]
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2. Fichtenbaum C J, Gerber J G, Rosenkranz S L. et al Pharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047. AIDS 200216569–577.577 [PubMed]
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3. Gerber J G, Rosenkranz S L, Fichtenbaum C J. et al Effect of efavirenz on the pharmacokinetics of simvastatin, atorvastatin, and pravastatin: results of AIDS Clinical Trials Group 5108 Study. J Acquir Immune Defic Syndr 200539307–312.312 [PubMed]
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Articles from Sexually Transmitted Infections are provided here courtesy of BMJ Group
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