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YUN LU, PHARM.D., is Hospital Pharmacy Specialist in Cardiology, Department of Pharmacy; and KATIE A. WON, PHARM.D., is Hospital Pharmacy Specialist in Hematology/Oncology, Department of Pharmacy, Hennepin County Medical Center (HCMC), Minneapolis, MN. BRENDA J. NELSON, PHARM.D., is Hospital Pharmacy Specialist, Allina Pharmacy Service, Abbott Northwestern Hospital, Minneapolis; at the time of writing she was Hospital Pharmacy Specialist, Department of Pharmacy, HCMC. DONGFENG QI, PH.D., is Senior Statistician, Department of Research, Cardiac Rhythm and Disease Management, Medtronic, Moundsview, MN; at the time of writing he was Senior Statistician, Department of Pharmacy, HCMC. DOUGLAS J. RAUSCH, M.D., is Hematologist/Oncologist and Division Head, Department of Hematology/Oncology; and RICHARD W. ASINGER, M.D., is Cardiology and Division Head, Department of Cardiology, HCMC.

Address correspondence to Dr. Lu at the Department of Pharmacy, Hennepin County Medical Center, 701 Park Avenue, Minneapolis, MN 55415 (yun.lu{at}hcmed.org).

Purpose. Characteristics of the amiodarone–warfarin interaction during long-term follow-up were studied. Methods. Medical records from patients seen in the anticoagulation clinic at the Hennepin County Medical Center between April 1998 and March 2003 were retrospectively reviewed. Patients were included if they were older than 18 years, used the anticoagulation clinic as their primary clinic for anticoagulation therapy, and were receiving combined amiodarone and warfarin therapy for at least one month. The primary study endpoint was the occurrence of International Normalized Ratios (INRs) of >5 at any time during combined warfarin–amiodarone therapy. The secondary endpoint was the frequency of warfarin dosage changes. Results. A total of 70 patients met study inclusion criteria. Of these 70, 7 had amiodarone started before warfarin initiation. Of the 2434 INR values analyzed, 43% (n = 1043) were in the target therapeutic range, 34% (n = 820) were below target range, and 23% (n = 571) were above target range. A total of 102 INR values (4%) were above 5. The relative risk of having an INR of >5 for patients on concurrent warfarin and amiodarone versus those on warfarin alone was 1.366 (p = 0.005). INRs of >5 were most common during the first 12 weeks of combined therapy, with no subsequent large peaks evident. Conclusion. Among patients treated in an anticoagulation clinic, INR values of >5 were most common during the first 12 weeks of combined therapy with amiodarone and warfarin and necessitated reduction in warfarin dosage. No other notable changes in INR or amiodarone or warfarin dosage occurred throughout the remainder of the 80-week study period. Index terms: Amiodarone; Anticoagulants; Cardiac drugs; Dosage; Drug interactions; International normalized ratio; Pharmacokinetics; Warfarin