Drug Interactions between ibrexafungerp and voriconazole

ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.

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.

The recommended maximum number of medicines in the 'antifungal agents' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'antifungal agents' category:

• ibrexafungerp
• voriconazole

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.