Drug Interactions between Cibinqo and lemborexant

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of lemborexant, which is primarily metabolized by CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice but has been reported for other CYP450 3A4 inhibitors. When coadministered with itraconazole, a potent CYP450 3A4 inhibitor, lemborexant peak plasma concentration (Cmax) and systemic exposure (AUC) increased approximately 1.4-fold and 3.8-fold, respectively. When coadministered with fluconazole, a moderate CYP450 3A4 inhibitor, lemborexant Cmax and AUC increased approximately 1.6-fold and 4.2-fold, respectively. 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. Increased exposure to lemborexant may increase the risk of adverse reactions such as central nervous system (CNS) depression, sleep paralysis, hallucinations, complex sleep behaviors, worsening of depression or suicidal ideation, nightmares, palpitations, or headache.

After administration of a high-fat, high-calorie meal (approximately 1000 calories with 500 to 600 calories from fat), lemborexant Cmax decreased by 23%, AUC increased by 18%, and the time to maximum concentration (Tmax) was delayed by 2 hours.

MANAGEMENT: The manufacturer makes no recommendation regarding administration with food; however, the time to sleep onset may be delayed if taken with or soon after a meal. Patients should avoid consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with lemborexant.

MONITOR: Smoking during treatment with abrocitinib may increase the risk of major adverse cardiovascular events (MACE) and the risk of developing malignancies. During abrocitinib clinical studies, current or past smokers had an additional increased risk of overall malignancies. Also, abrocitinib may increase patients' risk of MACE, including myocardial infarction, stroke, and cardiovascular death.

Administration of abrocitinib with high-fat, high-calorie food increased abrocitinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 29% and 26%, respectively, and prolonged the time to reach Cmax by 2 hours. These changes are not considered clinically relevant.

MANAGEMENT: Caution is advised if abrocitinib is prescribed to current or past smokers. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. The manufacturer recommends discontinuing abrocitinib in patients that have experienced a myocardial infarction or stroke. Abrocitinib may be taken with or without food.