Simvastatin drug interactions

A 45-year-old male takes simvastatin for hypercholesterolemia however, his cholesterol level remains above target at maximal doses. Cholestyramine is added to the therapeutic regimen. What drug-drug interaction can occur ... 

Hypersensitivity to any component of the product. Coadministration of nelfinavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (eg, amiodarone, quinidine, ergot derivatives, pimozide, midazolam, triazolam, lovastatin, simvastatin see Drug Interactions). 

Lin JC, Ito MK. A drug interaction between troglitazone and simvastatin. Diabetes Care 1999 22(12) 2104-6. 

Most drug interactions associated with rhabdomyolysis occur when ciclosporin is combined with simvastatin or lovastatin. It has been suggested that if a statin is to be combined with ciclosporin, pravastatin or fluvastatin should be chosen instead (80). 

A potential drug interaction between simvastatin and danazol, causing rhabdomyolysis and acute renal insufficiency, has been reported (43). Rhabdomyolysis can occur with all statins when they are used alone and particularly when they are combined with other drugs that are themselves myotoxic or that increase the concentration of the statin. Statins are particularly susceptible to the latter effect because of their metabolism by the CYP450 system and their low oral systemic availability. 

Andreou ER. Potential drug interaction between simvastatin and danazol causing rhabdomyolysis. Can J Clin Pharmacol 2003 10 172-4. 

Lee AJ, Maddix DS. Rhabdomyolysis secondary to a drug interaction between simvastatin and clarithromycin. Ann Pharmacother 2001 35(1) 26-31. 

Ishigam M, Uchiyama M, Kondo T, Iwabuchi H, Inoue S, Takasaki W, Ikeda T, Komai T, Ito K, Sugiyama Y. 2001. Inhibition of in vitro metabolism of simvastatin by itraconazole in humans and prediction of in vivo drug-drug interactions. Pharm Res 18 622-631. 

Since HMG CoA reductase inhibitors (statins) are partially or completely metabolized by CYP3A4, drug interactions with protease inhibitors can be expected. When nelfinavir was combined with atorvastatin and simvastatin, their AUCs increased by 74 and 505% respectively (17). As myopathy and rhabdomyolysis are concentration-related, simvastatin is contraindicated with any protease inhibitor, not just nelfinavir. Based on the data, the starting dose of atorvastatin should be reduced by about 50%. 

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