Drug Interactions between aprocitentan and dasabuvir / ombitasvir / paritaprevir / ritonavir

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inducers of uridine 5'-diphospho-glucuronosyltransferase (UDP-glucuronosyltransferase or UGT) enzymes may decrease the systemic exposure and effects of aprocitentan, which is primarily metabolized by UGT1A1 and UGT2B7. Some UGT inducers are associated with similar adverse effects to those of aprocitentan, such as hepatotoxicity (e.g., alcohol, carbamazepine, efavirenz, fosphenytoin, phenytoin, rifampin). It is unclear if the use of aprocitentan with these substances could increase the risk of similar adverse effects. Clinical data examining aprocitentan with inducers of UGT are not available.

MANAGEMENT: Caution and clinical monitoring for reduced efficacy may be advised if aprocitentan is used with a UGT inducer. If the UGT inducer also shares a similar adverse effect profile with aprocitentan, like hepatotoxicity, additional monitoring for the adverse effect in question may also be recommended. Additional monitoring may also be beneficial if a UGT inducer is added to or withdrawn from the patient's regimen during aprocitentan therapy.

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inhibitors of CYP450 2C8 may increase the plasma concentrations of dasabuvir, which is primarily metabolized by the isoenzyme. In 11 study subjects, the potent CYP450 2C8 inhibitor gemfibrozil given at 600 mg twice daily increased single-dose dasabuvir peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 2- and 11-fold, respectively. The risk of ALT elevations and QT prolongation may be increased.

MANAGEMENT: Caution is advised if dasabuvir is prescribed in combination with CYP450 2C8 inhibitors. Patients should be monitored for development of hepatotoxicity (i.e., ALT elevations) and QT interval prolongation.