Beware of the Simvastatin/Amiodarone Drug Interaction

For electrophysiologists, the drug combinations of amiodarone (marketed as Cordarone® or Pacerone®) and simvastatin (marketed as Zocor®) is a common drug combination. The FDA issued an alert that these two drugs, when taken together, might result in an increased incidence of rhabdomyolysis (injury to muscle cells characterized by muscle aches, weakness and dark urine). It is thought by some that this might result from competition of the two drugs for the same metabolic pathway in the liver:

Statins such as atorvastatin (Lipitor®), lovastatin (Mevacor®) and simvastatin (Zocor®)are metabolised via a cytochrome P450 3A-dependent pathway while fluvastatin (Lescol®), pravastatin (Pravachol®)and rosuvastatin (Crestor®) are metabolised via cytochrome P450 3A-independent pathways. As simvastatin and amiodarone are metabolised by the same isoenzyme, in the present case, the concomitant use of these drugs may have resulted in competition, resulting in excess of free plasma statin and thereby causing myotoxicity. However, there are limited publications on this interaction and the exact mechanism has not been established.

It is recommended to keep the daily simvastatin dose to 20 mg or less to avoid this side effect of the drug combination.

-Wes

h/t: WSJ.