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Clinical InvestigationsCardiologyClinical Observations With the Amiodarone/Warfarin Interaction: Dosing Relationships With Long-term Therapy
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.