To evaluate a stereoselective interaction for
amiodarone and racemic
warfarin, we performed a prospective study with its separated enantiomorphs. Single oral doses of racemic
warfarin, 1.5 mg/kg, were administered to six normal subjects, with and without oral
amiodarone, 400 mg daily, for the hypoprothrombinemic duration. Both the
hypoprothrombinemia (P less than 0.001) and plasma
warfarin concentrations (P less than 0.01) were significantly increased. The experiments were repeated separately with the R- and S-
warfarin enantiomorphs. S-
warfarin with
amiodarone significantly increased both the
hypoprothrombinemia (P less than 0.001) and plasma
warfarin concentrations (P less than 0.01). R-
warfarin with
amiodarone significantly increased both the
hypoprothrombinemia (P less than 0.001) and plasma
warfarin concentrations (P less than 0.001). Thus
amiodarone augmented the
anticoagulant effect nonstereoselectively by reduced metabolic clearance of both
warfarin enantiomorphs.
Amiodarone and racemic
warfarin can be a dangerous combination, particularly when either
drug is added to a stabilized regimen of the other
drug, unless the prothrombin times are monitored carefully.