Interactions between efavirenz and Voriconazole (voriconazole)
efavirenz and voriconazole (Major Drug-Drug)
ADJUST DOSE: Coadministration with efavirenz may significantly decrease the plasma concentrations of voriconazole. The mechanism of interaction has not been described but may involve efavirenz induction of voriconazole metabolism via CYP450 isoenzymes. According to voriconazole labeling, efavirenz (400 mg once a day for 9 days) decreased the steady-state peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of voriconazole (400 mg every 12 hours for 1 day, then 200 mg every 12 hours for 8 days) by an average of 61% and 77%, respectively, in healthy subjects. In contrast, voriconazole increased the steady-state Cmax and AUC of efavirenz by an average of 38% and 44%, respectively. When voriconazole (400 mg twice a day) and efavirenz (300 mg once a day) were coadministered, the changes in Cmax and AUC were considered clinically insignificant.
MANAGEMENT: The use of standard doses of voriconazole with efavirenz is considered contraindicated. If concurrent administration is necessary, the manufacturer recommends an increased voriconazole maintenance dose of 400 mg twice a day and a 50% reduction of the efavirenz dose to 300 mg once daily.
