Drug Interaction Report

GENERALLY AVOID: Coadministration with ceftobiprole may increase the plasma concentrations and the risk of adverse effects of drugs that are substrates of organic anion transporting polypeptide (OATP) 1B1 and/or OATP1B3. The proposed mechanism is decreased clearance due to ceftobiprole-mediated inhibition of OATP1B1 and/or OATP1B3.

MANAGEMENT: Concomitant use of ceftobiprole with drugs that are substrates of OATP1B1 and/or OATP1B3 is not recommended. Clinical and laboratory monitoring may be appropriate whenever ceftobiprole is added to or withdrawn from therapy with these drugs. Dosage adjustments may be considered if an interaction is suspected. Patients should be monitored for the development of adverse effects.

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.

ADJUST DOSING INTERVAL: Administration with food enhances the oral bioavailability of sofosbuvir, velpatasvir, and voxilaprevir. Relative to fasting conditions, mean sofosbuvir systemic exposure (AUC) increased by 64% to 144%, mean velpatasvir AUC increased by 40% to 166%, and mean voxilaprevir AUC increased by 112% to 435% when the combined sofosbuvir/velpatasvir/voxilaprevir formulation is administered with food.

MANAGEMENT: Sofosbuvir/velpatasvir/voxilaprevir should be administered with food.