Drug Interactions between ivacaftor / lumacaftor and seladelpar

MONITOR: Coadministration with inhibitors of the breast cancer resistance protein (BCRP) may increase the plasma concentrations and effects of seladelpar, which is a substrate of this efflux transporter. A clinical drug interaction study found that the systemic exposure (AUC) and maximum plasma concentration (Cmax) of a single dose of seladelpar (10 mg) increased by 2.1- and 2.9-fold, respectively, when administered with a single dose of the BCRP inhibitor cyclosporine (600 mg) in healthy subjects.

MANAGEMENT: Close monitoring for adverse reactions is advised if seladelpar is administered concurrently with a BCRP inhibitor. Liver tests should be monitored as clinically indicated and treatment with seladelpar may need to be held or permanently discontinued if liver tests worsen and/or clinical hepatitis develops. The labeling of the inhibitor should also be consulted as some inhibitors may continue to have effects on this transporter even after the agent has been discontinued.

GENERALLY AVOID: Concomitant administration with inhibitors of the organic anion transporter 3 (OAT3) may increase the plasma concentrations of seladelpar, which is a substrate of this renal transporter. Administration of the OAT3 inhibitor probenecid (500 mg four times daily) to healthy subjects on days 1 through 4, with a single dose of seladelpar (10 mg) administered on day 2 resulted in an increase of seladelpar's systemic exposure (AUC) and maximum plasma concentration (Cmax) of 2- and 4.69-fold, respectively. Additionally, the mean cumulative urinary excretion of seladelpar was unquantifiable in the presence of probenecid, compared to 2.1 mcg in the absence of probenecid.

MANAGEMENT: Concurrent use of seladelpar with OAT3 inhibitors should generally be avoided.