Drug Interactions between rucaparib and sofosbuvir / velpatasvir / voxilaprevir

MONITOR: Coadministration with rucaparib may increase the plasma concentrations and the risk of adverse effects of drugs that are substrates of CYP450 3A4. The proposed mechanism is decreased clearance due to rucaparib-mediated inhibition of CYP450 3A4. In a clinical study, rucaparib increased midazolam Cmax and AUC by 1.13- and 1.38-fold, respectively.

MANAGEMENT: Caution is advised if rucaparib is used concomitantly with drugs that are substrates of CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever rucaparib is added to or withdrawn from therapy with these drugs. Patients should be monitored for the development of adverse 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.