Drug Interactions between Dexilant SoluTab and sofosbuvir / velpatasvir / voxilaprevir

GENERALLY AVOID: Coadministration of velpatasvir with proton pump inhibitors 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 37% and 36%, respectively, when a single 400 mg-100 mg dose of sofosbuvir-velpatasvir was administered simultaneously with omeprazole 20 mg once daily. Interestingly, mean sofosbuvir Cmax and AUC also decreased by 34% and 29%, respectively, although its solubility is not known to be pH-dependent. When omeprazole 20 mg once daily was given 12 hours before the sofosbuvir-velpatasvir dose, mean velpatasvir Cmax and AUC decreased by 57% and 55%, respectively, while mean sofosbuvir Cmax and AUC decreased by 45% and 44%, respectively. Similar results were observed for velpatasvir when omeprazole 20 mg once daily was given 2 hours before the sofosbuvir-velpatasvir dose, or when omeprazole 40 mg once daily was given 4 hours after the sofosbuvir-velpatasvir dose. When omeprazole 20 mg once daily was administered 4 hours after the sofosbuvir-velpatasvir dose, mean velpatasvir Cmax decreased by 33% and AUC decreased by 26%.

MANAGEMENT: Concomitant use of sofosbuvir-velpatasvir with proton-pump inhibitors should generally be avoided. If coadministration is required, sofosbuvir-velpatasvir should be administered with food and taken 4 hours before the proton-pump inhibitor at a maximum daily dose equivalent to omeprazole 20 mg. Use with other proton-pump inhibitors has not been studied.

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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.

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