Drug Interaction Report

CONTRAINDICATED: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of doravirine, which is primarily metabolized by the isoenzyme. When a single 100 mg dose of doravirine was administered with the potent CYP450 3A4 inducer rifampin (600 mg once daily) in 10 study subjects, doravirine peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (C24hr) decreased by an average of 57%, 88% and 97%, respectively, compared to doravirine administered alone. Reduced efficacy of doravirine may occur.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, concomitant use of doravirine with potent CYP450 3A4 inducers is considered contraindicated. At least a 4-week cessation period is recommended prior to initiation of doravirine treatment.