Drug Interaction Report

ADJUST DOSE: Coadministration with rifabutin may significantly decrease the plasma concentrations of doravirine. The mechanism is rifabutin induction of doravirine metabolism via CYP450 3A4. When a single 100 mg dose of doravirine was administered with rifabutin 300 mg once daily in 12 study subjects, doravirine peak plasma concentration (Cmax) did not change, but systemic exposure (AUC) and trough plasma concentration (C24hr) decreased by an average of 50% and 68%, respectively, compared to doravirine administered alone. Reduced efficacy of doravirine may occur.

MANAGEMENT: When used with rifabutin, doravirine dosage should be increased to 100 mg twice daily (approximately 12 hours apart) for the duration of rifabutin coadministration. Otherwise, doravirine should not be initiated until at least 4 weeks after cessation of rifabutin.