Drug Interactions between sodium citrate and sofosbuvir / velpatasvir / voxilaprevir

ADJUST DOSING INTERVAL: Concurrent administration of velpatasvir with drugs that elevate gastric pH such as antacids may reduce its gastrointestinal absorption. Velpatasvir exhibits pH-dependent solubility, with increased solubility at lower pH. Drugs that increase gastric pH are expected to decrease the plasma concentration of velpatasvir.

MANAGEMENT: If an antacid is required, the antacid should be taken 4 hours before or 4 hours after administration of sofosbuvir-velpatasvir. The same precaution may be applicable to other drugs with antacid 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.