Interaction between amiodarone (marketed as CORDARONE and PACERONE) and simvastatin (marketed as ZOCOR and generics) or simvastatin-combination products (marketed as VYTORIN and SIMCOR)
Amiodarone potentiates the risk for simvastatin-associated rhabdomyolysis
FDA continues to receive reports of rhabdomyolysis in patients given amiodarone in combination with higher doses of simvastatin. Amiodarone is an antiarrhythmic drug indicated to treat certain types of recurrent ventricular arrhythmias. Simvastatin is a 3-hydroxy-methylglutaryl-coenzyme A reductase inhibitor (statin) used to lower cholesterol levels. As with all statins, the risk of rhabdomyolysis is dose-related and increased by high plasma levels of statin. Patients who take amiodarone with simvastatin doses greater than 20 mg daily have an increased risk of rhabdomyolysis. The precise mechanism for this drug interaction is unknown, but stems, in part, from amiodarone's inhibition of the cytochrome P450 3A4 (CYP3A4) enzyme, the same enzyme that metabolizes simvastatin (see Illustration 1). This interaction may result in an increase in the levels of simvastatin in the plasma, potentiating the risk of rhabdomyolysis. Labeling for all of the amiodarone (Cordarone and the generic drug Pacerone)1 and simvastatin-containing products [Zocor2, ezetimibe/simvastatin (Vytorin3) and niacin/simvastatin (Simcor4)] describe this potential risk.
Rhabdomyolysis, a severe form of myopathy, involves injury to and breakdown of skeletal muscles, which in some cases leads to renal failure and death.5 There are multiple etiologies for rhabdomyolysis, including, but not limited to, exposure to certain drugs, including statins.6,7 Healthcare professionals should be aware of the increased risk of rhabdomyolysis when amiodarone is taken concomitantly with doses of simvastatin that exceed 20 mg daily. Prescribers should avoid doses of simvastatin greater than 20 mg per day in patients taking amiodarone (the maximum recommended simvastatin dose is 80 mg daily).
Cardiac medications can be life-saving. They have dramatically improved the outcomes of patients with heart disease. However, there are always side effects, toxicities and interactions that we need to be aware of. Please be sure that you bring an up to date list of medications with you to your appointment so that we may be review the medications you are taking.
If you have any questions, please call us at (860) 714-7977. We would be happy to discuss this with you.