Chest
Volume 121, Issue 1, January 2002, Pages 19-23
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Clinical Investigations
Cardiology
Clinical Observations With the Amiodarone/Warfarin Interaction: Dosing Relationships With Long-term Therapy

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Objectives

The interaction between amiodarone and warfarin has only been described in patients being followed up for relatively short time periods. The objectives of this study were to characterize the interaction between these two agents in a clinical situation over a longer period of time in a larger cohort of patients, and to determine the relationship between the maintenance dose of amiodarone and the resultant need to adjust the dose of warfarin.

Design

This was an observational trial of a cohort of patients receiving a stable warfarin regimen in whom oral amiodarone was initiated. Patients received both amiodarone and warfarin for at least 1 year, and the dosage of warfarin was adjusted as clinically necessary to achieve an international normalized ratio of 2 to 3. Data from a total of 43 patients were analyzed.

Results

At baseline, prior to initiation of amiodarone, the warfarin dose was 5.2 ± 2.6 mg/d. The magnitude of the interaction between these two agents peaked at 7 weeks, which resulted in a 44% mean maximum reduction in the warfarin dose. The warfarin dose inversely correlated with the maintenance dose of amiodarone (r2 = 0.94, p < 0.005). Minor bleeding episodes occurred in five patients (12%). For patients receiving amiodarone maintenance doses of 400, 300, 200, or 100 mg/d, it is recommended that the daily warfarin dose be reduced by approximately 40%, 35%, 30%, or 25%, respectively.

Conclusions

The magnitude of the amiodarone/warfarin interaction is highly dependent on the maintenance dose of amiodarone. This relationship can aid clinicians in adjusting the dose of warfarin patients receiving long-term amiodarone treatment.

Section snippets

Materials and Methods

Between March 1, 1992, and February 28, 1998, records at the University of Illinois at Chicago were screened for patients receiving concomitant amiodarone and warfarin therapy. Patients were included in the analysis if oral amiodarone was added to existing warfarin therapy and the combination of the two drugs was continued for at least 1 year. Patients receiving other drugs known either to prolong the prothrombin time (PT) or INR or to interact with warfarin were subsequently excluded from the

Results

A total of 43 patients (26 male, 17 female; 62 ± 12 years of age) met the inclusion criteria and were included in the analysis. Amiodarone was used for the treatment of atrial fibrillation and/or atrial flutter in 33 patients, sustained or nonsustained ventricular tachycardia in 9 patients, and paroxysmal atrial tachycardia in 1 patient. Patients received long-term warfarin treatment for the following indications: atrial/flutter fibrillation (23 patients), prosthetic valve (9 patients), dilated

Discussion

Amiodarone causes a substantial decrease in the dose of warfarin required to achieve a therapeutic INR in all patients receiving this drug combination. Commercially, warfarin is available as a racemate of the (-)-S- and (+)-R- enantiomers; the (-)-S- enantiomer is about five times more potent as an anticoagulant.1920 The (-)-S- and the (+)-R- enantiomers are stereoselectively metabolized by hepatic isozymes CYP2C9 and CYP1A2, respectively. Amiodarone inhibits the activity of both of these P450

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Presented in part at the American College of Cardiology 47th Annual Scientific Session, Atlanta, GA, March 29 to April 1, 1998.

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