Major
Fluconazole × Warfarin
Antifungals, triazole derivatives×Vitamin K antagonist anticoagulants
Mechanism
Fluconazole inhibits CYP2C9, the main enzyme of S-warfarin (the more active isomer). INR rises to 8–12 with risk of major bleeding: gastrointestinal, intracranial, retroperitoneal.
Symptoms
By days 3–5: gum and nose bleeding, petechiae, haematuria, bloody stool. INR above 6 without clinical bleeding still requires action.
Management
If fluconazole is required, reduce warfarin by 25–50% from day 1 and check INR on days 3 and 7. Short courses (3 single doses) – INR check on day 5. After fluconazole withdrawal, retitrate warfarin upward.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.