Drug information of lemborexant

lemborexant

Drug group:

Lemborexant is a brain-penetrant, small molecule orexin/hypocretin receptor antagonist used to treat insomnia.
The neuropeptide orexin regulates wakefulness; inhibiting orexin receptor signaling promotes sleep. Lemborexant has been reported to inhibit the orexin signaling pathway and promote both REM and non-REM sleep in mice and rats;

lemborexant

Mechanism of effect

The mechanism of action of lemborexant in the treatment of insomnia is presumed to be through antagonism of orexin receptors. The orexin neuropeptide signaling system plays a role in wakefulness. Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R is thought to suppress wake drive.

Pharmacodynamic

Lemborexant is a novel dual orexin receptor antagonist used in the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance.
 lemborexant and other orexin antagonists (e.g. [suvorexant]) act to counteract inappropriate wakefulness. This novel mechanism of action offers potential advantages over classic hypnotic agents, including a more favorable adverse effect profile and potentially greater efficacy, and may signal the beginning of a new wave of treatment options for patients suffering from insomnia.
Lemborexant binds to orexin receptors OX1R and OX2R and acts as a competitive antagonist (IC50 values of 6.1 nM and 2.6 nM, respectively). A major metabolite of lemborexant, M10, binds with comparable affinity as the parent drug to orexin receptors OX1R and OX2R (IC50 values of 4.2 nM and 2.9 nM), respectively.

Pharmacokinetics

The time to peak levels of lemborexant is 1 to 3 hours. A high-fat and high-calorie meal has been found to delay the time to peak levels by 2 hours. Its plasma protein binding in vitro is 94%. Lemborexant is metabolized primarily by CYP3A4 and to a lesser extent by CYP3A5. The elimination half-life of lemborexant is 17 to 19 hours. The medication is excreted in feces (57%) and to a lesser extent urine (29%).

Drug indications

lemborexant is an orexin receptor antagonist indicated for the treatment of adult patients with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance.

Dosage

Recommended dose is 5 mg taken no more than once per night, immediately before going to bed, with at least 7 hours remaining before the planned time of awakening. Dosage may be increased to 10 mg based on clinical response and tolerability.
  • The maximum recommended dose is 10 mg once daily.
  • Time to sleep onset may be delayed if taken with or soon after a meal.

Drug contraindications

contraindicated in patients with narcolepsy

Side effects

    • The most common adverse reaction (reported in ≥5% of patients treated with lemborexant and at least twice the rate of placebo was somnolence.

Interactions

Pregabalin , Danazol , Drospirenone , Doxepin , Hydroxyzine , Carbamazepine , Butalbital and Acetaminophen , Quazepam , Cariprazine , Opium , oleandomycin , Gefitinib , Dasatinib , Sarecycline , voxelotor , ethotoin , Brivaracetam , tucatinib , Netupitant , Nicotine
Strong or moderate CYP3A inhibitors: Avoid concomitant use.
· Weak CYP3A inhibitors: The maximum recommended dose is 5 mg.
· Strong or moderate CYP3A inducers: Avoid concomitant use.

Alerts

    • CNS Depressant Effects and Daytime Impairment: Impairs alertness and motor coordination including morning impairment. Risk increases with dose and use with other central nervous system (CNS) depressants. For patients taking DAYVIGO 10 mg, caution against next-day driving and other activities requiring complete mental alertness.
    • Sleep Paralysis, Hypnogogic/Hypnopompic Hallucinations, and Cataplexy-like Symptoms: May occur with use of DAYVIGO.
    • · Complex Sleep Behaviors: Behaviors including sleep-walking, sleep-driving, and engaging in other activities while not fully awake may occur. Discontinue immediately if a complex sleep behavior occurs.
    •  · Compromised Respiratory Function: Effect on respiratory function should be considered
    • · Worsening of Depression/Suicidal Ideation: Worsening of depression or suicidal thinking may occur. Prescribe the lowest number of tablets feasible to avoid intentional overdosage
    • · Need to Evaluate for Co-morbid Diagnoses: Reevaluate if insomnia persists after 7 to 10 days of treatment.
    • DAYVIGO is a central nervous system (CNS) depressant that can impair daytime wakefulness even when used as prescribed. CNS depressant effects may persist in some patients for up to several days after discontinuing DAYVIGO. Prescribers should advise patients about the potential for nextday somnolence. Driving ability was impaired in some subjects taking DAYVIGO 10 mg [see Clinical Studies . The risk of daytime impairment is increased if DAYVIGO is taken with less than a full night of sleep remaining or if a higher than recommended dose is taken [see Dosage and Administration. If DAYVIGO is taken in these circumstances, patients should be cautioned against driving and other activities requiring complete mental alertness. Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression, which can cause daytime impairment. Dosage adjustments of DAYVIGO and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects. The use of DAYVIGO with other drugs to treat insomnia is not recommended. Patients should be advised not to consume alcohol in combination with DAYVIGO because of additive effects [see Drug Interactions. Because DAYVIGO can cause drowsiness, patients, particularly the elderly, are at a higher risk of falls.

Pregnancy level

There is a pregnancy exposure registry that monitors pregnancy outcomes in women who are exposed to DAYVIGO during pregnancy.

Breast feeding warning

There are no data on the presence of lemborexant in human milk, the effects on the breastfed infant, or the effects on milk production.

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