Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 1A2 may increase the plasma concentrations of bendamustine, which has been shown in vitro to be metabolized by the isoenzyme.

MANAGEMENT: Caution is advised if bendamustine is used in combination with CYP450 1A2 inhibitors. Close monitoring for toxicity (e.g., neutropenia, thrombocytopenia, anemia, leukopenia, infections, bleeding complications) is recommended, and the bendamustine dosage adjusted as necessary.

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).