Drug Interactions between atogepant and sofosbuvir / velpatasvir / voxilaprevir

ADJUST DOSE: Coadministration with inhibitors of organic anion transporting polypeptide (OATP) 1B1 and/or 1B3 may significantly increase the plasma concentrations of atogepant, which is a substrate of the hepatic uptake transporters. When atogepant was administered in healthy study subjects with single-dose rifampin, an OATP 1B1/1B3 inhibitor, atogepant peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 2.2- and 2.9-fold, respectively.

MANAGEMENT: The recommended dosage of atogepant is 10 mg or 30 mg once daily when used concomitantly with OATP 1B1/1B3 inhibitors.

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.