Drug Interactions between lenacapavir and tecovirimat

MONITOR: Coadministration with drugs that are inducers of the CYP450 3A4 isoenzyme may decrease the plasma concentrations of lenacapavir which may lead to diminished virologic response. The proposed mechanism is increased clearance due to induction of CYP450 3A4, which is partly responsible for the metabolism of lenacapavir. In pharmacokinetic studies conducted in fasted subjects without HIV, coadministration of a single oral dose of lenacapavir 300 mg with the potent CYP450 3A4 inducer rifampin 600 mg once daily decreased the systemic exposure (AUC) and peak plasma concentration (Cmax) of lenacapavir by approximately 84% and 55%, respectively. In the same studies, coadministration of a single oral dose of lenacapavir 300 mg with the moderate CYP450 3A4 inducer efavirenz 600 mg once daily decreased the AUC and Cmax of lenacapavir by approximately 56% and 36%, respectively. No data are available for other, less potent CYP450 3A4 inducers.

MANAGEMENT: The potential for reduced viral susceptibility and resistance development associated with subtherapeutic antiviral drug levels should be considered during coadministration of lenacapavir with CYP450 3A4 inducers. Alternative treatments may be considered if an interaction is suspected.