Drug Interactions between Diflucan and voriconazole

GENERALLY AVOID: Coadministration with fluconazole may significantly increase the plasma concentrations of voriconazole. The mechanism is fluconazole inhibition of CYP450 2C9 and 3A4, the isoenzymes responsible for the metabolic clearance of voriconazole. When oral voriconazole (400 mg every 12 hours on day 1, then 200 mg every 12 hours for 2.5 days) was given in combination with oral fluconazole (400 mg on day 1, then 200 mg every 24 hours for 4 days) in six healthy male subjects, voriconazole peak plasma concentration (Cmax) and systemic exposure (AUC) increased by an average of 57% and 79%, respectively. In a follow-up clinical study involving 8 healthy male subjects, reduced dosages and/or dosing frequency of voriconazole and fluconazole did not eliminate or diminish this effect.

GENERALLY AVOID: Both fluconazole and voriconazole can cause QT interval prolongation. Coadministration may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death.

MANAGEMENT: Concomitant administration of fluconazole and voriconazole at any dosage is not recommended. Close monitoring for adverse events related to voriconazole is recommended if voriconazole is used sequentially after fluconazole, especially within 24 hours of the last dose of fluconazole.