Interactions between Ibrexafungerp and Sucrets Ice

Coadministration with orally administered menthol may decrease plasma concentrations of drugs that are substrates of the CYP450 3A4 and/or CYP450 2C9 isoenzymes. The proposed mechanism is increased clearance due to menthol-mediated induction of CYP450 3A4 and CYP450 2C9. In vivo data suggests that concomitant administration of oral menthol reduced the systemic exposure (AUC) of triazolam (a CYP450 3A4 substrate) by 40%, and phenytoin (a CYP450 2C9 substrate) by 20%. Until further data are available, no specific precautions are recommended.

Generally avoid

Coadministration with grapefruit juice may increase the plasma concentrations of ibrexafungerp. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. 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. In healthy subjects receiving the potent CYP450 3A4 inhibitor ketoconazole (400 mg once daily for 15 days), ibrexafungerp peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2.5-fold and 5.8-fold, respectively. Increased plasma concentrations of ibrexafungerp may increase the risk for adverse effects such as diarrhea, nausea, abdominal pain, dizziness, and vomiting. When administered to healthy volunteers with a high-fat meal (800 to 1000 calories; 50% fat), ibrexafungerp Cmax and AUC increased 32% and 38%, respectively, compared to fasted conditions.

Management

Ibrexafungerp may be administered with or without food. However, avoiding consumption of grapefruit or grapefruit juice during treatment with ibrexafungerp may be advisable.