(1R,2S)-2-[[(2,4-Dimethyl-5-pyrimidinyl)oxy]methyl]-2-(3-fluorophenyl)-N-(5-fluoro-2-pyridinyl)cyclopropanecarboxamide

410.4166064

410.42

0K5743G68X

2245

77.00000

3.16

1.347±0.06 g/cm3(Predicted)

596.1±50.0 °C(Predicted)

314.3±30.1 °C

1.619

Clinical experience with lemborexant overdose is limited. In clinical studies, healthy patients receiving doses up to 10x the recommended maximum dose experienced dose-dependent increases in the frequency of adverse effects such as somnolence - it is likely, then, that symptoms of overdose will be consistent with lemborexant's adverse effect profile. In the event of an overdosage, implement supportive measures and consult the nearest poison control center for the most up to date management strategies. As lemborexant is highly protein-bound, hemodialysis is likely to be of little use in overdose situations.

In several clinical trials, lemborexant was found to be well tolerated, with serum ALT elevations above 3 times the upper limit of normal in less than 1% of treated subjects and with similar rates in placebo recipients. The elevations were transient and asymptomatic, none required dose modification or discontinuation, and none were associated with a simultaneous elevation in serum bilirubin. Thus, in the registration trials of lemborexant, there were no reports of clinically apparent liver injury. Lemborexant has been available for a limited period of time, but has yet to be implicated in causing clinically apparent liver injury with its more widespread clinical use.

Lemborexant is approximately 94% protein-bound _in vitro_, though the specific proteins to which it binds in plasma have not been elucidated.

Lemborexant is indicated for the treatment of adult patients with insomnia characterized by difficulties with sleep onset and/or sleep maintenance.|FDA Label

Lemborexant is an orexin receptor antagonist used for the treatment of insomnia and sleep disorders. Lemborexant therapy is associated with rare occurrence of transient serum enzyme elevations, but has not been implicated in cases of clinically apparent liver injury.

Sedatives and Hypnotics

Lemborexant promotes sleep by antagonizing the actions of wake-promoting chemicals in the brain. Episodes of complex sleep behaviors (e.g. eating food, having sex, making phone calls) have been reported in patients using lemborexant - these events may occur in hypnotic-naive and hyponotic-experienced patients, and patients are unlikely to remember these events. Patients exhibiting complex sleep behaviors should discontinue lemborexant immediately. Lemborexant may carry some risk of abuse, and should be used with caution in patients with a history of alcohol or drug addiction. Its controlled substance schedule is currently under review by the Drug Enforcement Administration.

Substances that bind to and inhibit the action of OREXIN RECEPTORS. Drugs in this class have been used as SLEEP AIDS, PHARMACEUTICAL. (See all compounds classified as Orexin Receptor Antagonists.)

Animal models of lemborexant disposition have demonstrated rapid absorption following oral administration. The T_max of lemborexant is approximately 1-3 hours, or 3-5 hours following administration of a high-fat, high-calorie meal. C_max and AUC_0-24h increase at a rate slightly less than proportionate to the given dose. Following administration of a high-fat, high-calorie meal, C_max is decreased by 23% and AUC_0-inf is increased by 18%. AUC, C_max, and terminal half-life are increased in the presence of moderate hepatic impairment, and AUC (but not half-life) is increased in the presence of mild hepatic impairment.|Following oral administration, 57.4% of the dose is found in the feces and 29.1% in the urine. Less than 1% of the dose recovered in the urine exists as unchanged parent drug, suggesting extensive metabolism.|The volume of distribution of lemborexant is 1970 L, indicating extensive tissue distribution.

Given that less than 1% of an administered dose is recovered unchanged in the urine, it is likely that lemborexant is extensively metabolized - this has been confirmed in rat and monkey models, but its metabolism in humans has not been fully characterized. Prescribing information states that it is predominantly metabolized by CYP3A4, with a smaller contribution by CYP3A5. The major circulating metabolite is lemborexant's M10 metabolite, which is pharmacologically active and binds to orexin receptors with a similar affinity to the parent drug. The M10 metabolite has the potential to induce CYP3A and CYP2B6 enzymes, weakly inhibit CYP3A enzymes, and is a substrate of P-gp transporters.

The half-life for lemborexant at doses of 5mg and 10mg is 17 and 19 hours, respectively.

The orexin neuropeptide signaling system is involved in many physiologic functions, including sleep/wake control. Orexin-A and orexin-B activate post-synaptic G-protein coupled orexin-1 receptors (OX1R) and orexin-2 receptors (OX2R), which are found on neurons in the hypothalamus that project to numerous wake-controlling nuclei. Each receptor carries slightly different activity - activation of OX1R appears to suppress the onset of rapid eye movement (REM) sleep, whereas activation of OX2R appears to suppress non-REM sleep. Lemborexant is an competitive antagonist of OX1R and OX2R. By blocking the binding of wake-promoting orexin-A and -B at these receptors, lemborexant suppresses the wake-drive, thereby promoting sleep.

(1R,2S)-2-(((2,4-dimethyl-5-pyrimidinyl)oxy)methyl)-2-(3-fluorophenyl)-N-(5-fluoro-2-pyridinyl)cyclopropanecarboxamide

Lemborexant|(1R,2S)-2-[(2,4-dimethylpyrimidin-5-yl)oxymethyl]-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropane-1-carboxamide|2245|Schedule IV - Substances in the DEA Schedule IV have a low potential for abuse relative to substances in Schedule III.|No

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients