Major
Established
Description
Fluconazole dramatically increases warfarin exposure, causing large INR elevations and a high risk of serious or life-threatening bleeding.
Mécanisme
Fluconazole is a potent CYP2C9 inhibitor and moderate CYP3A4 inhibitor, substantially reducing the clearance of both S- and R-warfarin enantiomers.
Signification clinique
S-warfarin AUC increases by ~90%; INR values can double or triple, with numerous case reports of major hemorrhage including intracranial bleeding.
Prise en charge
Avoid concomitant use if possible. If essential, reduce warfarin dose by 25–50%, monitor INR daily or every other day during fluconazole therapy, and for 7 days after stopping fluconazole.