Increased Warfarin Requirements during Concurrent Dicloxacillin Therapy

Abstract

Objective: To report on a patient who required increased dosages of warfarin to achieve therapeutic anticoagulation while taking dicloxacillin. Case Summary: A 60-year-old woman was hospitalized for an infected lymphocele and cellulitis. Based on microbiology results, dicloxacillin 500 mg by mouth 4 times daily was initiated to complete 14 days of treatment. Concurrently, a deep vein thrombosis was diagnosed by computed tomography angiography. Enoxaparin 100 mg subcutaneously twice daily and warfarin 5 mg by mouth daily were initiated with an international normalized ratio (INR) goal of 2–3. The patient had a history of a supratherapeutic INR while on warfarin 5 mg daily. Throughout the 20-day hospitalization, her warfarin dose was steadily increased in an attempt to achieve a therapeutic INR. Required doses ranged from 7.5 to 15 mg daily. Two days after discontinuation of dicloxacillin and with administration of a 15-mg warfarin boost, the INR was therapeutic at 2.3. Enoxaparin was discontinued and the patient was discharged on warfarin 7.5 mg daily. Upon clinic follow-up 5 days after discharge, the INR was supratherapeutic at 3.3 and the warfarin dose was decreased. The patient was then lost to follow-up. Discussion: This interaction between warfarin and dicloxacillin has been described in the literature; however, the mechanism responsible remains unknown. In all cases reported, increased warfarin requirements appeared after several days of dicloxacillin therapy and slowly disappeared after dicloxacillin discontinuation. This case differs from previously reported cases because it demonstrates warfarin resistance associated with dicloxacillin and a subsequent new initiation of warfarin therapy. The Naranjo probability scale and the Horn Drug Interaction Probability Scale both rate this interaction as probable. Conclusions: Patients taking dicloxacillin who are initiated on warfarin may require a longer duration of concurrent low-molecular-weight heparin therapy, as well as higher doses of warfarin, and may take longer to achieve a therapeutic INR.