Drug Interactions between lenacapavir and primidone

CONTRAINDICATED: Coadministration with drugs that are combined P-glycoprotein (P-gp), uridine diphosphate glucuronosyltransferase (UGT) 1A1, and potent inducers of CYP450 3A4, or sole potent inducers of CYP450 3A4 may decrease the plasma concentration of lenacapavir and result in a potential loss of virologic response. The proposed mechanism is increased clearance due to induction of the isoenzymes CYP450 3A4 and UGT1A1, which are primarily responsible for the metabolism of lenacapavir, as well as induction of P-gp, of which lenacapavir is a substrate. In pharmacokinetic studies conducted in fasted subjects without HIV, coadministration of a single oral dose of lenacapavir 300 mg with the combined P-gp, UGT1A1 and potent CYP450 3A4 inducer rifampicin 600 mg once daily decreased the systemic exposure (AUC) and peak plasma concentration (Cmax) of lenacapavir by approximately 84% and 55% respectively.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiviral drug levels, concomitant use of lenacapavir with drugs that are either combined P-gp, UGT1A1 and potent CYP450 3A4 inducers or sole potent inducers of CYP450 3A4 is considered to be contraindicated.