Drug Interactions between brigatinib and zaleplon

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

ADJUST DOSING INTERVAL: Administration of zaleplon with a high-fat or heavy meal may delay the onset of hypnotic effects. In healthy adult subjects, administration of zaleplon with a high-fat meal resulted in a 2-hour delay in the time to reach peak plasma drug concentration (Tmax) and a 35% reduction in the peak plasma drug concentration (Cmax) compared to fasting. Zaleplon systemic exposure (AUC) and elimination half-life were not significantly affected.

MANAGEMENT: Patients receiving zaleplon should be advised to avoid the consumption of alcohol. For faster sleep onset, zaleplon should not be administered with or immediately after a high-fat or heavy meal.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of brigatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. 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. Itraconazole, a potent CYP450 3A4 inhibitor, has been shown to double brigatinib systemic exposure (AUC) in healthy volunteers. Increased exposure to brigatinib may increase the risk of adverse effects such as nausea, vomiting, diarrhea, hypertension, bradycardia, hyperglycemia, visual disturbances, lymphopenia, anemia, and elevations in pancreatic enzymes and creatine phosphokinase.

Food does not significantly affect the oral bioavailability of brigatinib. When brigatinib was administered to healthy volunteers after a high-fat meal (920 calories; 59 g fat, 58 g carbohydrates, 40 g proteins), brigatinib peak plasma concentration (Cmax) decreased by 13% and systemic exposure (AUC) did not change compared to administration after overnight fasting.

MANAGEMENT: Brigatinib may be taken with or without food. Patients should avoid consumption of grapefruit and grapefruit juice during treatment with brigatinib.