Drug Interactions between everolimus and sofosbuvir / velpatasvir / voxilaprevir

MONITOR: Coadministration with inhibitors of CYP450 3A4 and/or P-glycoprotein may increase the blood concentrations of everolimus following oral administration. Everolimus is a substrate of both the CYP450 3A4 isoenzyme and P-glycoprotein drug efflux transporter, thus their inhibition in the intestine can enhance the absorption of everolimus.

MANAGEMENT: The possibility of prolonged and/or increased pharmacologic effects of everolimus therapy should be considered during coadministration with CYP450 3A4 and/or P-glycoprotein inhibitors, including adverse effects such as pneumonitis, stomatitis, infection, dyspnea, diarrhea, anemia, leucopenia, thrombocytopenia, hyperglycemia, and hyperlipidemia. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy.

MONITOR: Coadministration with inhibitors of CYP450 3A4 and/or P-glycoprotein may increase the blood concentrations of everolimus following oral administration. Everolimus is a substrate of both the CYP450 3A4 isoenzyme and P-glycoprotein drug efflux transporter, thus their inhibition in the intestine can enhance the absorption of everolimus.

MANAGEMENT: The possibility of prolonged and/or increased pharmacologic effects of everolimus therapy should be considered during coadministration with CYP450 3A4 and/or P-glycoprotein inhibitors, including adverse effects such as pneumonitis, stomatitis, infection, dyspnea, diarrhea, anemia, leucopenia, thrombocytopenia, hyperglycemia, and hyperlipidemia. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy.

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.