Drug Interaction Report

GENERALLY AVOID: Coadministration of leniolisib may increase plasma levels and systemic exposure to substrates of the hepatic uptake transporters organic anion transporting polypeptide (OATP) 1B1 and OATP 1B3, and/or the intestinal and hepatobiliary efflux transporter breast cancer resistance protein (BCRP). Leniolisib is an in vitro inhibitor of these transporters. However, clinical data are not available.

MANAGEMENT: According to the manufacturer of leniolisib, concomitant use with substrates of OATP 1B1, OATP 1B3, and/or BCRP should generally be avoided.

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).