Major
Established
Açıklama
Fluconazole dramatically increases warfarin exposure, causing large INR elevations and a high risk of serious or life-threatening bleeding.
Mekanizma
Fluconazole is a potent CYP2C9 inhibitor and moderate CYP3A4 inhibitor, substantially reducing the clearance of both S- and R-warfarin enantiomers.
Klinik Önemi
S-warfarin AUC increases by ~90%; INR values can double or triple, with numerous case reports of major hemorrhage including intracranial bleeding.
Yönetim
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.