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Am Fam Physician. 2002;65(8):1669-1670

Amiodarone is an effective medication used in the treatment of life-threatening ventricular arrhythmias. The advantage of amiodarone compared with similar antiarrhythmic agents is its minimal proarrhythmic effects. Studies also have shown that it does not increase the mortality risk. However, amiodarone does have complex interactions with multiple medications. The combination of amiodarone and warfarin potentiates the effect of warfarin and prolongs the International Normalized Ratio (INR), increasing the risk of bleeding. Despite the fact that this is a known result of interaction, the effect of this combination of medications has been reviewed only for short periods of time. Sanoski and colleagues studied the interaction between amiodarone and warfarin in patients receiving this combination of drugs for at least one year.

The observational trial included a cohort of patients who were receiving a stable dosage of warfarin when amiodarone was added to the treatment regimen. A total of 43 patients who took the combination of warfarin and amiodarone for at least one year were included in the study. Patients were excluded from participation if they were taking other medications that could affect the INR or interact with either of these medications. During the study, the dosage of warfarin was adjusted to maintain an INR of 2 to 3 in most patients. Amiodarone therapy was initiated in the hospital and titrated down to the standard dosage of 200 or 400 mg per day, based on the underlying cardiac pathology. The INR was measured every week initially, then monthly when the stable dosage was established.

Before starting amiodarone therapy, the average dose of warfarin was approximately 5 mg. The peak effect of amiodarone on the INR occurred at week 7, resulting in a 44 percent average reduction in the warfarin dosage. The study found that the impact of amiodarone on the INR was directly related to the maintenance dosage of this medication. The authors state that with amiodarone dosages of 400, 300, 200, or 100 mg per day, the warfarin dosage should be reduced by 40, 35, 30, or 25 percent, respectively. Minor episodes of bleeding occurred in 12 percent of the study subjects.

The authors conclude that the degree of interaction between amiodarone and warfarin is highly dependent on the maintenance dosage of amiodarone. Patients who receive stable dosages of warfarin but need amiodarone to control cardiac arrhythmias maybe managed by using the reductions based on the maintenance dosage of amiodarone. Using this information, physicians can better manage the INR in patients who require the combination of amiodarone and warfarin.

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Copyright © 2002 by the American Academy of Family Physicians.

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