Drug Interactions between sofosbuvir / velpatasvir / voxilaprevir and vadadustat

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.

MONITOR: Coadministration with vadadustat may increase the plasma concentrations of drugs that are substrates of the CYP450 3A4 and/or CYP450 2C8 isoenzymes. Vadadustat is an inhibitor of CYP450 3A4 and CYP450 2C8 in vitro. However, clinical data are not available.

MANAGEMENT: Some authorities recommend using caution when vadadustat is used concomitantly with drugs that are substrates of CYP450 3A4 and/or CYP450 2C8, particularly sensitive substrates or those with a narrow therapeutic range. Monitoring for signs and symptoms of increased exposure to the CYP450 3A4 and/or CYP450 2C8 substrate should be considered whenever vadadustat is added to or withdrawn from therapy. The prescribing information for concomitant medications may be consulted to assess the benefits versus risks of coadministration, as well as any dosage adjustments that may be required during coadministration and/or following the discontinuation of a CYP450 3A4 and/or CYP450 2C8 inhibitor.

MONITOR: Coadministration with vadadustat may increase the plasma concentrations of drugs that are substrates of the CYP450 3A4 and/or CYP450 2C8 isoenzymes. Vadadustat is an inhibitor of CYP450 3A4 and CYP450 2C8 in vitro. However, clinical data are not available.

MANAGEMENT: Some authorities recommend using caution when vadadustat is used concomitantly with drugs that are substrates of CYP450 3A4 and/or CYP450 2C8, particularly sensitive substrates or those with a narrow therapeutic range. Monitoring for signs and symptoms of increased exposure to the CYP450 3A4 and/or CYP450 2C8 substrate should be considered whenever vadadustat is added to or withdrawn from therapy. The prescribing information for concomitant medications may be consulted to assess the benefits versus risks of coadministration, as well as any dosage adjustments that may be required during coadministration and/or following the discontinuation of a CYP450 3A4 and/or CYP450 2C8 inhibitor.