Simvastatin hepatotoxicity

The UK Medicines and Healthcare Products Regulatory Agency (MHRA) data show that several deaths have occurred from hepatotoxicity. Most reports of hepatic adverse drug reactions (ADRs) relate to atorvastatin and simvastatin [36]. There are relatively fewer for pravastatin and fluvastatin. However, this may reflect their ... 

Ricuarte B, Guirguis A, Taylor HC, Zabri ie D. Simvastatin-amiodarone interaction result-ii in rhabdcmyolysis, azotemia, and possible hepatotoxicity. Ann Pharmacother (2006) 40, 753-7. 

It has been suggested that danazol (and the doxycycline) were possibly hepatotoxic, which led to decreased lovastatin metabolism, or that the danazol had a direct toxic effect on the muscles. Efanazol inhibits the cytochrome P450 isoenzyme CYP3A4 by which simvastatin and lovastatin are metabolised, which would result in raised statin levels, and therefore myopathy and rhabdomyolysis. This seems a more likely explanation for the effects seen. 

Liver Hepatotoxic events occasionally have been reported when ezetimibe is used in conjunction with a statin, as in the case of a 70-year-old woman who developed fulminant hepatic failure, necessitating liver transplantation 10 weeks after switching from simvastatin to simvastatin 4- ezetimibe[25]. A study with 32 subjects with nonalcoholic fatty liver disease pathology showed that ezetimibe improved hepatic fibrosis but increased hepatic long-chain fatty acids and HbA c [26]. 

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