Prospective study of the potentiation of acenocoumarol by amiodarone

Abstract

The influence of oral amiodarone on the anticoagulant effect of the coumarin derivative acenocoumarol has been investigated prospectively in 10 patients with normal renal, hepatic and haematological function and who were not in cardiac failure. The daily dose of acenocoumarol was sufficient to produce a prothrombin activity of 25 to 35%. When the prothrombin time had become stable amiodarone 600 mg/d was administered for 1 week followed by 400 mg/d for the next 3 weeks. A decrease in prothrombin activity from 30.5 to 20.2% was observed, associated with a decrease in vitamin K coagulation factors, after a mean of 4 days following commencement of amiodarone. In 6 patients a prothrombin activity less than 20% required a 60% reduction in the dose of acenocoumarol after 1 week of amiodarone 600 mg, and a 33% reduction after 3 weeks of amiodarone 400 mg. There was no correlation between the plasma amiodarone and the decrease in prothrombin activity. Inhibition of acenocoumarol metabolism by amiodarone is the most likely explanation of these findings.

Amiodarone-Acenocoumarin Interaction

“…the relationship between the maintenance daily dose of amiodarone and the reduction in oral anticoagulant requirements remains controversial: while some did (3), others did not (2) find a significant correlation. Moreover, serum amiodarone levels had no correlation with the decrease in prothrombin activity (5).…”

“…when orally administered, amiodarone showed a significative potentiating effect not before 4 to 7 days (2,3,5). the reduction in anticoagulant doses was extremely variable, ranging from 20% (3) to 60% (5).…”

“…while several papers showed the potentiating effect in all the reported cases (1), at least 121138 patients did not modify their coagulation activity after initiating amiodarone treatment (2,4,5).…”

“…Analysis of nearly 240 reported patients suffering from this interaction (1)(2)(3)(4)(5), pointed out several interesting differences among the conclusions drawn from evaluating single trials:…”

Effects of chronic treatment with amiodarone on hepatic demethylation and cytochrome P450

“…Case reports suggest possible pharmacokinetic interactions with warfarin, acenocoumarol, quinidine, digoxin, procainamide, phenytoin and aprindine. Only recently, however, has it been suggested that the underlying mechanism of many of these interactions may b e inhibition of the hepatic metabolism (McGovern et a1 1984;Saal et al 1984;Richard et al 1985).…”