Drug Interactions between ranitidine bismuth citrate and sofosbuvir / velpatasvir / voxilaprevir

ADJUST DOSE: Coadministration of velpatasvir with H2-receptor antagonists may reduce its gastrointestinal absorption. Velpatasvir exhibits pH-dependent solubility, with increased solubility at lower pH. In 60 healthy volunteers, mean velpatasvir peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 20% and 19%, respectively, when a single 400 mg-100 mg dose of sofosbuvir-velpatasvir was administered simultaneously with a 40 mg dose of famotidine. When the famotidine dose was given 12 hours before the sofosbuvir-velpatasvir dose, mean velpatasvir Cmax decreased by 13% and AUC decreased by 15%. These alterations are not considered clinically significant. However, higher dosages of famotidine or another H2-receptor antagonist may result in a greater magnitude of interaction.

MANAGEMENT: H2-receptor antagonists may be administered simultaneously with or 12 hours apart from sofosbuvir-velpatasvir at a dose that does not exceed the equivalent of famotidine 40 mg twice daily.

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.