Drug Interactions between atazanavir and lenacapavir

GENERALLY AVOID: Coadministration with combined uridine diphosphate glucuronosyltransferase (UGT) 1A1, P-glycoprotein (P-gp), and potent CYP450 3A4 inhibitors may significantly increase the plasma concentrations of lenacapavir. Lenacapavir is a substrate of CYP450 3A, P-gp, and UGT1A1. In pharmacokinetic studies conducted in fasted subjects without HIV, coadministration of a single oral dose of lenacapavir 300 mg with atazanavir/cobicistat 300 mg/150 mg once daily, a potent CYP450 3A4 inhibitor and inhibitor of P-gp and UGT1A1, increased systemic exposure (AUC) and peak plasma concentration (Cmax) of lenacapavir by approximately 4.2-fold and 6.6-fold, respectively. No clinically significant drug interactions with lenacapavir have been observed with potent CYP450 3A4 inhibitors such as voriconazole or potent CYP450 3A4 inhibitors and P-gp inhibitors such as cobicistat.

MANAGEMENT: Concomitant use of lenacapavir with combined UGT1A1, P-gp, and potent CYP450 3A4 inhibitors such as atazanavir (in combination with cobicistat or ritonavir) should generally be avoided.