Drug interactions between amiodarone and Zocor

ADJUST DOSE: The use of amiodarone with higher dosages of simvastatin or lovastatin may be associated with an increased risk of myopathy. In an ongoing clinical trial, myopathy has been reported in 6% of patients receiving simvastatin 80 mg and amiodarone. There is also a reported case of rhabdomyolysis in a patient who received simvastatin 40 mg with amiodarone for 2 weeks. The proposed mechanism is amiodarone inhibition of simvastatin metabolism via intestinal and hepatic CYP450 3A4, resulting in significantly enhanced bioavailability and reduced clearance of simvastatin. Although not studied, the interaction is also expected to occur with lovastatin due to its similar metabolic profile to simvastatin. In general, the risk of myopathy associated with the statin class of drugs is thought to be dose-related and increased by high levels of HMG-CoA reductase inhibitory activity in plasma. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death.

MANAGEMENT: Simvastatin dosage should generally not exceed 20 mg daily and lovastatin dosage not exceed 40 mg daily when used in combination with amiodarone unless the clinical benefit is anticipated to outweigh the increased risk of myopathy. Fluvastatin, pravastatin, and rosuvastatin are probably safer alternatives in patients receiving amiodarone, since they are not metabolized by CYP450 3A4. All patients treated with HMG-CoA reductase inhibitors should be advised to promptly report any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.