Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of apremilast, which is primarily metabolized by the isoenzyme in vitro. According to the product labeling, administration of a single 30 mg oral dose of apremilast with the potent CYP450 inducer rifampin (600 mg once daily for 15 days) resulted in decreases of apremilast peak plasma concentration (Cmax) and systemic exposure (AUC) by 43% and 72%, respectively.

MANAGEMENT: The possibility of a diminished therapeutic response to apremilast should be considered during coadministration with CYP450 3A4 inducers. Pharmacologic effects of apremilast should be monitored more closely following the initiation or withdrawal of a CYP450 3A4 inducer.

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.