Elevated International Normalized Ratio Associated with Use of Dronedarone and Warfarin

Abstract

To describe a case of elevated international normalized ratio (INR) after addition of dronedarone to warfarin therapy. A 72-year-old white female with a history of tinnitus, gastroesophageal reflux disease, and permanent pacemaker implantation was taking warfarin (target INR 2-3) and sotalol for chronic atrial fibrillation; atorvastatin for hyperlipidemia; and risedronate for osteopenia. Her warfarin therapy had been managed by a nurse-run anticoagulation clinic for several years. During the prior year, her INR had been stable with a weekly dose of warfarin 25 mg. After persistent episodes of atrial fibrillation, the antiarrhythmic agent was changed from sotalol to dronedarone 400 mg twice daily. Approximately 10 days after starting dronedarone, the INR was 4.8; she stated that there was no bleeding. The warfarin dose was decreased to 20 mg/wk, and the INR remained stable with that dosage for the next 11 months. Postmarketing surveillance has revealed cases of increased INR values with or without bleeding in patients taking warfarin who were started on dronedarone. In this case, the Horn Drug Interaction Probability Scale suggested a probable causality for an interaction between dronedarone and warfarin. Based on current knowledge, this interaction may involve an indirect gastrointestinal mechanism and/or a direct pharmacokinetic mechanism. Clinicians should monitor patients who are taking warfarin and dronedarone for INR changes and bleeding episodes about 1 week after initiation of dronedarone. If a significant interaction is noted, the warfarin dosage should be decreased and the patient should be monitored within 2 weeks to assess the need for further adjustments.