OBJECT DRUGS

Anticoagulants, Oral:

• Acenocoumarol
• Warfarin (Coumadin, etc.)

PRECIPITANT DRUGS

Azole Antifungals:

• Fluconazole (Diflucan)
• Miconazole (Monistat, etc.)
• Voriconazole (Vfend)

Comment:

Fluconazole is a potent inhibitor of CYP2C9, and even at a dose of 100 mg/day can substantially increase the hypoprothrombinemic response of warfarin. Miconazole also strongly inhibits S-warfarin metabolism. Several cases have been reported of marked increase in warfarin effect following the use of miconazole oral gel, probably because the oral gel was swallowed and absorbed. Vaginal miconazole has also increased warfarin response in isolated cases. Topical administration of miconazole on the skin has been reported to increase warfarin effect, but the effect appears to be rare.

Class 2: Use Only if Benefit Felt to Outweigh Risk

• Use Alternative: Itraconazole (Sporanox), ketoconazole (Nizoral), posaconazole (Noxafil), and terbinafine (Lamisil) probably have less effect on warfarin metabolism than other azole antifungals. Nonetheless, isolated cases of increased warfarin effect have been reported, and one should still monitor for increased warfarin response.
• Monitor: Monitor for altered hypoprothrombinemic response if an azole antifungal is initiated, discontinued, or changed in dosage.