Drug Interactions between lemborexant and octreotide

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.

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MONITOR: Due to their gastrointestinal pharmacologic effects, somatostatin analogs (e.g., octreotide, lanreotide) may variously affect the absorption of dietary nutrients and concomitantly administered oral medications. Somatostatin analogs have been shown to prolong gastrointestinal transit time and inhibit intestinal absorption of some nutrients such as fat. Clinical data are limited, however. In case reports, octreotide has been reported to reduce the relative bioavailability of cyclosporine. Transplant rejection and significant reductions in cyclosporine levels, sometimes to undetectable levels, have been reported in association with the interaction. Vitamin K absorption was not affected when concomitantly administered with lanreotide according to the manufacturer.

MANAGEMENT: Clinicians should be aware of the potential for altered absorption of concomitantly administered oral medications during treatment with somatostatin analogs. Blood levels and clinical response should be monitored, particularly for drugs that have a narrow therapeutic index, and the dosages adjusted as necessary.

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