Fluconazole × Warfarin

Fluconazole strongly inhibits CYP2C9, the key clearance route for S-warfarin. INR may rise 2- to 3-fold within 5–10 days. The effect is dose-dependent: it becomes clinically significant at fluconazole doses of 200 mg/day or above.

Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.

For a short fluconazole course (up to 7 days), empirically reduce warfarin by 30–50% and check INR every 3 days. For prolonged systemic mycosis therapy, switch to echinocandins (micafungin, caspofungin) or titrate warfarin to INR.