Possible Amiodarone−Warfarin Interaction: A Reemphasis on a Potentially Dangerous Drug−Drug Interaction

Abstract

This article reports two patients with delayed amiodarone— warfarin interaction resulting in a significant elevation in the international normalized ratio. One patient developed episodes of nosebleeds. Amiodarone is a potent inhibitor of the cytochrome P450 enzyme system. Warfarin undergoes metabolism via the same isoenzyme, potentially leading to prolongation of elevated international normalized ratio levels. A decrease in the warfarin dose is thus warranted when coadministered with amiodarone to circumvent the potential danger of this interaction, which can go unnoticed because several weeks of therapy may be necessary to discern an elevated international normalized ratio. The Naranjo probability scale indicated a possible relationship between the elevated international normalized ratio levels and the coadministration of amiodarone and warfarin. With the coadministration of warfarin and amiodarone, frequent and close monitoring of warfarin is paramount, especially in the initial weeks of therapy, in an effort to prevent supratherapeutic international normalized ratios and bleeding complications.