Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may 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. The extent to which other, less potent CYP450 3A4 inducers may interact with leniolisib is unknown.

MANAGEMENT: The potential for diminished pharmacologic effects of leniolisib should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected. Patients should be advised to notify their physician if their symptoms worsen or their condition changes.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of rufinamide. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: Food enhances the oral absorption and bioavailability of rufinamide. In healthy volunteers, administration of a single 400 mg dose of rufinamide with food resulted in an approximately 56% increase in mean peak plasma concentration (Cmax) and a 34% increase in systemic exposure (AUC) compared to administration during a fasting state.

MANAGEMENT: To ensure maximal oral absorption, it is preferable to administer rufinamide with food. Patients receiving rufinamide should be advised to avoid consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how rufinamide affects them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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).