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.

MONITOR: Coadministration with enzalutamide may decrease the plasma concentrations of drugs that are substrates of CYP450 3A4, 2C9, 2C19, and/or P-glycoprotein (P-gp) efflux transporter. The proposed mechanism involves accelerated clearance via these routes due to enzalutamide-mediated induction. The resulting plasma concentrations will depend on the sensitivity of the affected drugs to these isoenzymes.

MANAGEMENT: Caution is advised when enzalutamide is used concomitantly with drugs that are substrates of CYP450 3A4, 2C9, 2C19, and/or P-gp, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever enzalutamide is added to or withdrawn from therapy.

Food enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate. According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state. However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state. Food delays the time to reach tenofovir Cmax by approximately 1 hour. Tenofovir disoproxil fumarate may be administered without regard to meals.