Drug Interaction Report

MONITOR: Coadministration with drugs that are moderate inhibitors of CYP450 3A4 may increase the plasma concentrations of leniolisib, which is primarily metabolized by the isoenzyme. Physiological-based pharmacokinetic (PBPK) modeling predicts that concomitant use with the moderate CYP450 3A4 inhibitor, erythromycin, may lead to an increase in systemic exposure (AUC 0-12h) of leniolisib by 75%. Increased exposure to leniolisib may increase the risk of adverse effects such as headache, sinusitis, and atopic dermatitis. Clinical data are not available.

MANAGEMENT: Caution and monitoring are advisable, particularly following initiation, discontinuation, or change of dosage of the moderate CYP450 3A4 inhibitor in people stabilized on their leniolisib therapy. Some authorities recommend to avoid concomitant use of moderate CYP450 3A4 inhibitors and leniolisib (UK).

ADJUST DOSING INTERVAL: Food enhances the absorption and oral bioavailability of darunavir administered in combination with low-dose ritonavir. The mechanism is unknown. When administered with food, the peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of darunavir were approximately 30% higher than when administered in the fasting state. Darunavir exposure was similar for the range of meals studied. The total caloric content of the various meals evaluated ranged from 240 Kcal (12 grams fat) to 928 Kcal (56 grams fat).

MANAGEMENT: To ensure maximal oral absorption, darunavir coadministered with ritonavir should be taken with food. The type of food is not important.

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).