Drug Interactions between sofosbuvir / velpatasvir / voxilaprevir and zavegepant

MONITOR: Coadministration with inhibitors of organic anion transporting polypeptides (OATP) 1B1 and/or 1B3 may increase the plasma concentrations of voxilaprevir, which is a substrate of the hepatic uptake transporters. When a single 100 mg dose of voxilaprevir was administered with a single 600 mg dose of the potent OATP 1B1/1B3 inhibitor cyclosporine (n=24), mean voxilaprevir peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 19.0- and 9.4-fold, respectively. Inhibition of P-glycoprotein (P-gp)- and breast cancer resistance protein (BCRP)-mediated intestinal transport and CYP450 3A4-mediated metabolism of voxilaprevir may also contribute to the overall interaction with cyclosporine. The safety of such high levels of voxilaprevir has not been established.

MANAGEMENT: Caution and monitoring are advised when voxilaprevir is used with OATP 1B1 or 1B3 inhibitors.

GENERALLY AVOID: Coadministration with inhibitors of the organic anion transporting polypeptide (OATP) 1B3 hepatic uptake transporter and/or the hepatic bile acid uptake transporter sodium taurocholate co-transporting polypeptide (NTCP) may significantly increase the plasma concentrations and effects of zavegepant, which is a substrate of these transporters. When single-dose oral zavegepant (100 mg) was administered with the OATP 1B3 and NTCP inhibitor and strong CYP450 3A4 inducer, rifampin, at steady state, zavegepant peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 2.2- and 2.3-fold, respectively.

MANAGEMENT: Concomitant use of zavegepant with OATP 1B3 and/or NTCP inhibitors should generally be avoided.

GENERALLY AVOID: Coadministration with inhibitors of the organic anion transporting polypeptide (OATP) 1B3 hepatic uptake transporter and/or the hepatic bile acid uptake transporter sodium taurocholate co-transporting polypeptide (NTCP) may significantly increase the plasma concentrations and effects of zavegepant, which is a substrate of these transporters. When single-dose oral zavegepant (100 mg) was administered with the OATP 1B3 and NTCP inhibitor and strong CYP450 3A4 inducer, rifampin, at steady state, zavegepant peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 2.2- and 2.3-fold, respectively.

MANAGEMENT: Concomitant use of zavegepant with OATP 1B3 and/or NTCP inhibitors should generally be avoided.