WASHINGTON, DC. Well over a thousand cases of rhabdomyolysis (an often fatal muscle disease) caused by the ingestion of statin drugs (atorvastatin [Lipitor], simvastatin [Zocor], lovastatin [Mevacor], pravastatin [Pravachol]) have been reported. Now the FDA has issued a warning not to take more than 20 mg/day of simvastatin if also taking amiodarone since doing so will markedly increase the risk of rhabdomyolysis. The warning also applies to the combination of simvastatin and ezetimibe (Vytorin) and the combination of simvastatin and extended-release niacin (Simcor). The FDA press release states that:

• The risk of rhabdomyolysis is increased when higher doses of simvastatin are administered with amiodarone. The precise mechanism is unknown, but is related to the fact that amiodarone inhibits the cytochrome P450 3A4 (CYP3A4) enzyme. This is the same enzyme that metabolizes simvastatin. Prescribers should consider use of another statin for patients taking amiodarone, or initiating amiodarone therapy, who require simvastatin doses greater than 20 mg daily to meet their lipid goals.

• Rhabdomyolysis has been reported with all statins. Predisposing risk factors for rhabdomyolysis include advanced age (greater than 65 years), uncontrolled hypothyroidism, and renal impairment.

• The FDA does not have data on how varying the dose of amiodarone in patients taking simvastatin affects the risk of developing rhabdomyolysis.

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Editor�s comment: If a combination of amiodarone and 20 mg/day or more of simvastatin is dangerous enough to require a warning, how dangerous is amiodarone plus 10 mg/day? Who knows? The FDA does not seem to. What is perhaps more disturbing is that the FDA has no data regarding the effect of amiodarone dosage on rhabdomyolysis incidence when combined with simvastatin. Could simvastatin combined with a loading dose of amiodarone (800 � 1600 mg/day) be vastly more dangerous than the combination of simvastatin and an amiodarone maintenance dose of 200 � 400 mg/day? Nobody knows, so afibbers on or contemplating amiodarone should be very careful about also taking statin drugs, particularly simvastatin.