Drug Interaction Report

GENERALLY AVOID: Coadministration of leniolisib may increase plasma levels of substrates of the CYP450 1A2 isoenzyme. According to in vitro studies, leniolisib is a time-dependent irreversible inhibitor of CYP450 1A2. However, clinical data are not available.

MANAGEMENT: Caution and monitoring are recommended if leniolisib is to be administered in combination with CYP450 1A2 substrates. According to the manufacturer of leniolisib, its concomitant use of CYP450 1A2 substrates with a narrow therapeutic index 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).