Dronedarone and vitamin K antagonists: A review of drug-drug interactions

Adverse drug events affect millions of patients each year. An important drug-drug interaction between amiodarone and vitamin K antagonists is encountered frequently in daily clinical practice. Warfarin, a commonly used anticoagulant, is a mixture of 2 optically active isomers (R and S enantiomers). The S enantiomer is approximately 3 times more potent than the R enantiomer and is metabolized primarily by CYP2C9. Inhibition of CYP2C9 by amiodarone and its major metabolite potentiates the anticoagulant effects of warfarin, increasing the risk of serious bleeding. In contrast, dronedarone, a synthetic derivative of amiodarone the structure of which lacks the iodine moiety, is less likely to cause a drug-drug interaction with warfarin. Accordingly, dronedarone may be a particularly attractive antiarrhythmic choice among patients with atrial fibrillation who are also being treated with warfarin.