Warfarin Resistance with Nafcillin Therapy

Drug-induced warfarin resistance may be mediated by the direct effect of a drug on warfarin's absorption, excretion, distribution, or metabolism. A 29-year-old man on long-term stable anticoagulation therapy with warfarin sodium developed resistance to warfarin while receiving nafcillin. His prothrombin time ranged between 14 and 17 s (control, 12 s) despite an increase in his warfarin dosage to 25 mg/d. Pharmacokinetic studies showed that the decreased hypoprothrombinemic effect of warfarin was most likely due to rapid metabolism of the anticoagulant induced by nafcillin. Warfarin's half-life was 11 hours when the patient was on nafcillin therapy and 44 hours when he was off nafcillin therapy. This interaction may be clinically important in patients requiring concomitant administration of nafcillin and warfarin.