Drug Interaction Report

GENERALLY AVOID: Coadministration with moderate to potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations and pharmacologic effects of leniolisib. The proposed mechanism is accelerated clearance of leniolisib due to induction of the CYP450 3A4 isoenzyme, which is the primary route of elimination of leniolisib. Pharmacokinetic-based physiologic modeling predicts that concomitant use of leniolisib with the potent CYP450 3A4 rifampin or moderate CYP450 3A4 inducer efavirenz may decrease the systemic exposure (AUC 0-12h) of leniolisib by 78% and 58%, respectively. Loss of therapeutic efficacy may occur; however, clinical data are not available.

MANAGEMENT: The use of leniolisib with moderate to potent CYP450 3A4 inducers should generally be avoided. Alternative therapeutic agents with less enzyme induction potential should be considered whenever possible.

ADJUST DOSING INTERVAL: Coadministration with food increases the oral bioavailability of etravirine. The mechanism is unknown. Compared to administration following a meal, the systemic exposure (AUC) to etravirine was decreased by about 50% when the drug was administered under fasting conditions. The types of meal studied (ranging from 345 kilocalories containing 17 grams fat to 1160 kilocalories containing 70 grams fat) did not appear to make a difference with respect to impact on etravirine bioavailability.

MANAGEMENT: Etravirine should always be administered following a meal.

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).