Drug Interaction Report

MONITOR: Coadministration with sarecycline may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) transporter. The proposed mechanism is decreased clearance in the intestine, kidney, and/or liver due to inhibition of P-gp-mediated efflux by sarecycline. When the probe P-gp substrate digoxin was coadministered with a single 150 mg dose of sarecycline, digoxin peak plasma concentration (Cmax) increased by 26%.

MANAGEMENT: Caution is advised when sarecycline is used concurrently with drugs that are P-gp substrates, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever sarecycline is added to or withdrawn from therapy.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.

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.