Which drug increases warfarin effect (↑INR)?

• A. Fluconazole
• B. Phenytoin
• C. Rifampin
• D. Multivitamins

Answer: (A)

Warfarin is cleared mainly by the liver enzyme CYP2C9. Drugs that inhibit this enzyme slow warfarin’s metabolism, causing higher blood levels and a higher INR, which means more anticoagulation and a greater bleeding risk. Fluconazole is a potent inhibitor of CYP2C9, so when it’s given with warfarin, INR tends to rise more than with warfarin alone—making it the drug that increases warfarin’s effect.

In contrast, phenytoin and rifampin induce hepatic enzymes, which speeds up warfarin metabolism and lowers the INR, reducing anticoagulation. Multivitamins can affect warfarin too, often through vitamin K content, which can counteract warfarin and reduce INR or add variability, but they do not reliably raise INR like fluconazole. When starting fluconazole in someone on warfarin, closely monitor INR and adjust the warfarin dose as needed to avoid bleeding.