Drug Interactions between brincidofovir and Vosevi

GENERALLY AVOID: Coadministration with inhibitors of the hepatic influx transporters organic anion transporting polypeptides (OATP) 1B1 and 1B3 may increase the plasma concentrations and adverse effects of brincidofovir. In clinical studies, coadministration with a single 600 mg oral dose of the OATP1B1 and 1B3 inhibitor cyclosporine increased the mean systemic exposure (AUC) and peak plasma concentration (Cmax) of brincidofovir by 374% and 269%, respectively.

MANAGEMENT: The manufacturer advises that, where possible, coadministration of brincidofovir with OATP1B1 or 1B3 inhibitors should be avoided and alternative medicines considered. However, if concomitant use is necessary, administration of the OATP1B1 or 1B3 inhibitor should be postponed by at least 3 hours after the administration of brincidofovir. Patients should also be closely monitored for brincidofovir-related adverse reactions such as elevations in hepatic transaminases and bilirubin, diarrhea, nausea, vomiting, and abdominal pain.

GENERALLY AVOID: Coadministration with inhibitors of the hepatic influx transporters organic anion transporting polypeptides (OATP) 1B1 and 1B3 may increase the plasma concentrations and adverse effects of brincidofovir. In clinical studies, coadministration with a single 600 mg oral dose of the OATP1B1 and 1B3 inhibitor cyclosporine increased the mean systemic exposure (AUC) and peak plasma concentration (Cmax) of brincidofovir by 374% and 269%, respectively.

MANAGEMENT: The manufacturer advises that, where possible, coadministration of brincidofovir with OATP1B1 or 1B3 inhibitors should be avoided and alternative medicines considered. However, if concomitant use is necessary, administration of the OATP1B1 or 1B3 inhibitor should be postponed by at least 3 hours after the administration of brincidofovir. Patients should also be closely monitored for brincidofovir-related adverse reactions such as elevations in hepatic transaminases and bilirubin, diarrhea, nausea, vomiting, and abdominal pain.

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.