Warfarin and Fluconazole Interaction in a Patient with Atrial Fibrillation and Candidiasis
A 68-year-old woman with atrial fibrillation is on warfarin 5 mg daily, with a stable INR of 2.5 (target 2.0–3.0). She weighs 70 kg, has normal renal and hepatic function, and takes no other medications. She presents with oral candidiasis and is prescribed fluconazole 200 mg orally on day 1, then 100 mg daily for 7 days. Four days later, she returns with gum bleeding and bruising. Her INR is 6.8. She denies missed doses, dietary changes, or alcohol use. The pharmacist must manage the interaction and prevent future events.
1. Explain the mechanism of the warfarin–fluconazole interaction and calculate an appropriate warfarin dose adjustment based on the expected magnitude of the interaction.
Read the worked answer
Fluconazole is a potent inhibitor of CYP2C9, the primary enzyme metabolizing S-warfarin (the more active enantiomer). It also inhibits CYP3A4 to a lesser extent. This reduces warfarin clearance, increasing INR. The interaction typically raises INR by 2- to 3-fold within 3–5 days. For a patient on warfarin 5 mg daily with a stable INR of 2.5, starting fluconazole 100–200 mg daily would likely increase INR to supratherapeutic levels. A common approach is to reduce the warfarin dose by 25–50% (e.g., to 2.5–3.75 mg daily) and monitor INR every 2–3 days. In this case, the INR of 6.8 with bleeding requires holding warfarin and administering vitamin K1 2.5 mg orally (or 1–2 mg IV if severe bleeding). After stabilization, restart warfarin at a reduced dose (e.g., 2.5 mg daily) and continue INR monitoring. The pharmacist should counsel the patient on bleeding signs and avoid unnecessary fluconazole use.
2. What monitoring plan and patient education would you recommend to prevent recurrence?
Read the worked answer
Monitor INR every 2–3 days during fluconazole therapy and for 1 week after discontinuation, as the enzyme inhibition resolves slowly. Educate the patient to report any bleeding (gum bleeding, bruising, dark urine, black stools) immediately. Advise avoiding over-the-counter azoles and other CYP2C9 inhibitors. Provide a written anticoagulation record. Consider alternative antifungal (e.g., nystatin oral suspension) for future candidiasis if appropriate, to avoid interaction. Emphasize consistent vitamin K intake and alcohol avoidance. Document the interaction in the patient's record and communicate with the prescriber.