Possible interaction between warfarin and fluconazole

Fluconazole is a triazole antifungal agent reported to have a low affinity for human cytochrome P-450, and thus would not be expected to interact with drugs metabolized through the cytochrome P-450 system, including phenytoin, cyclosporine, and warfarin. A potential interaction between warfarin and fluconazole occurred in a 39-year-old man with chronic renal insufficiency. He was receiving anticoagulant therapy for a lower extremity thrombus and oral fluconazole 50 mg/day for a fungal urinary tract infection. After attaining consistent international normalized ratio (INR) values between 2.0 and 2.7 with warfarin, the INR increased to 5.2 four days after fluconazole was started, despite decreasing the dosage of warfarin. There were no changes in the patient's other medications, and the INR decreased to 1.5 on discontinuation of fluconazole. The possible mechanism of an interaction may be dose-related inhibition of warfarin metabolism, and may be more pronounced in patients with decreased renal clearance of fluconazole.