Absolute Contraindications for Lemborexant
Lemborexant is absolutely contraindicated in patients with narcolepsy or history of cataplexy, as it can trigger narcolepsy-like symptoms including cataplexy, sleep paralysis, and hypnagogic/hypnopompic hallucinations. 1, 2
Primary Contraindications
Narcolepsy or history of cataplexy: Lemborexant can trigger narcolepsy-like symptoms even in patients without a history of narcolepsy 1, 3
Hyperactive delirium: Case reports show lemborexant can trigger cataplexy and sleep attacks in patients with hyperactive delirium 1
Complex sleep behaviors: Patients with history of complex sleep behaviors (sleep walking, sleep driving, etc.) should avoid lemborexant due to risk of similar behaviors 2
Severe hepatic impairment: As with other orexin receptor antagonists, severe liver disease is a contraindication due to altered drug metabolism 4
Safety Concerns Requiring Caution
Pregnancy or breastfeeding: Limited safety data exists for use during pregnancy or lactation 2
Concomitant CNS depressants: Combined use with other CNS depressants may potentiate sedative effects 4
Alcohol: Concurrent use with alcohol is contraindicated due to additive CNS depression 4
Strong CYP3A4 inhibitors/inducers: Lemborexant is metabolized by CYP3A4/5, and strong inhibitors or inducers can significantly alter drug levels 2
Suicidal ideation: Patients with history of suicidal thoughts require careful monitoring as orexin antagonists may cause emergence of depression or suicidal ideation 2
Monitoring Considerations
Next-day impairment: Lemborexant should be taken at least 7 hours before planned awakening to minimize residual effects 2, 5
Driving performance: While studies show minimal impact on driving 8-9 hours after administration compared to placebo, patients should be cautioned about potential impairment 4, 6
Psychiatric disorders: Patients with psychiatric conditions require close monitoring as efficacy and safety have not been adequately investigated in major mental disorders 2
Clinical Context
Lemborexant is a dual orexin receptor antagonist approved for insomnia treatment. While it effectively improves sleep onset and maintenance 5, 6, its mechanism of blocking orexin signaling can potentially induce narcolepsy-like symptoms, particularly in vulnerable populations 1, 3. Unlike some other hypnotics, lemborexant appears to have minimal residual effects and withdrawal symptoms 2, 6, but the risk of cataplexy and other narcolepsy-like symptoms must be carefully considered, especially when combined with emotional triggers 3.