Amiodarone × Simvastatin

Amiodarone inhibits CYP3A4, the enzyme that metabolises simvastatin. In a study cited in the US simvastatin label (FDA), amiodarone 400 mg a day raised the AUC of simvastatin and its active acid form about 1.75-fold. Higher levels raise the risk of myopathy and rhabdomyolysis: in a clinical study, myopathy occurred in 6% of patients taking simvastatin 80 mg with amiodarone (simvastatin SmPC).

Muscle pain, tenderness or weakness with creatine kinase (CK) above 10 times the upper limit of normal. In rhabdomyolysis, urine turns dark from myoglobin and acute kidney injury may follow.

The combination is not contraindicated, but the simvastatin dose is capped: no more than 20 mg a day, and higher doses with amiodarone are avoided (simvastatin SmPC). The US simvastatin and amiodarone labels (FDA) set the same limit. The amiodarone SmPC recommends a statin that is not metabolised by CYP3A4 during co-administration. Warn the patient about myopathy and ask them to report unexplained muscle pain, tenderness or weakness promptly (simvastatin SmPC).