Drug Interactions between brentuximab and sofosbuvir / velpatasvir / voxilaprevir

MONITOR: Coadministration with inhibitors of P-glycoprotein (P-gp) may increase the plasma concentrations of monomethyl auristatin E (MMAE), the microtubule-disrupting component of brentuximab vedotin. In vitro, MMAE was found to be a substrate of the P-gp efflux transporter.

MANAGEMENT: Caution is advised when brentuximab is used with P-gp inhibitors. Close monitoring for adverse effects including neutropenia, infection, peripheral neuropathy, and hepatotoxicity is recommended.

MONITOR: Coadministration with inhibitors of P-glycoprotein (P-gp) may increase the plasma concentrations of monomethyl auristatin E (MMAE), the microtubule-disrupting component of brentuximab vedotin. In vitro, MMAE was found to be a substrate of the P-gp efflux transporter.

MANAGEMENT: Caution is advised when brentuximab is used with P-gp inhibitors. Close monitoring for adverse effects including neutropenia, infection, peripheral neuropathy, and hepatotoxicity is recommended.

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.