Effect of carbamazepine initiation and discontinuation on antithrombotic control in a patient receiving warfarin: case report and review of the literature

A 72-year-old Caucasian woman with paroxysmal atrial fibrillation had been taking warfarin therapy for 5 years with a stable international normalized ratio (INR). Her dentist then prescribed carbamazepine 200 mg/day to control facial nerve pain. At her next physician visit about 2 weeks after the start of the carbamazepine, the patient's INR had dropped from 3.3 to 1.3; she reported no contributing changes in her diet or warfarin dosage, nor had she taken other interacting drugs. Her warfarin dosage was increased, and the INR returned to the target range of 2.0-3.0 approximately 2 months later. The patient's INR remained stable for approximately 6 more months, until she had facial surgery. During that time, her warfarin was discontinued for 5 days, and the patient had stopped taking the carbamazepine because she had no pain. One month later, her INR increased from 2.2 to 3.6. She did not experience any thrombotic or hemorrhagic episodes. Warfarin undergoes hepatic metabolism through cytochrome P450 2C9, and carbamazepine induces this isoenzyme. Inducing warfarin metabolism necessitates an increase in the warfarin dosage to maintain the INR in the therapeutic target range. To our knowledge, this is the first report documenting the effect of the carbamazepine initiation and discontinuation in a patient receiving anticoagulation therapy with warfarin. In patients taking warfarin, clinicians should monitor the INR closely when carbamazepine is started or discontinued, or when either dosage is changed.