Drug Interactions between brincidofovir and leniolisib

ADJUST DOSING INTERVAL: Administration with food decreases the oral bioavailability of brincidofovir. According to the product labeling, administration of brincidofovir tablets with a low-fat meal (approximately 400 calories, 25% of calories from fat) was associated with a reduction in the systemic exposure (AUC) and peak plasma concentration (Cmax) of brincidofovir by 31% and 49%, respectively, compared to administration under fasting. However, no clinically meaningful changes in intracellular concentrations of cidofovir diphosphate were observed. The effect of food on the oral suspension formulation has not been evaluated.

MANAGEMENT: Brincidofovir oral tablets and suspension should be taken on an empty stomach. If necessary, the oral tablets may be taken with a low-fat 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).