Drug Interaction Report

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.

MONITOR: Coadministration with inhibitors of CYP450 3A4 including grapefruit or grapefruit juice may increase the plasma concentrations of leniolisib, which undergoes extensive CYP450 3A4-mediated first-pass metabolism in the gut wall and liver. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of leniolisib. Some authorities recommend to avoid grapefruit products during leniolisib treatment (UK).