Section 10 · Monograph

Lemborexant

Reviewed Nov 2026FDA label

DayvigoOrexin receptor antagonist

Indications

Treatment of insomnia in adults, characterized by difficulties with sleep onset and/or sleep maintenance.FDA-labeled

Limited off-label use reported for insomnia comorbid with mild obstructive sleep apnea (studied in trials without significant respiratory depressant effect at that severity, but formal indication does not extend to moderate-severe OSA).Off-label

Lemborexant is a dual orexin receptor antagonist (DORA), in the same pharmacologic class as suvorexant (Belsomra).
Antagonizes orexin receptor subtypes OX1R and OX2R, blocking binding of the wake-promoting neuropeptides orexin A and orexin B.
By suppressing orexin-mediated wake drive rather than directly potentiating GABAergic inhibition, lemborexant is thought to promote sleep onset and maintenance through a distinct neurobiological pathway from Z-drugs/benzodiazepines.

Adults: 5 mg orally once nightly, immediately before bedtime, with at least 7 hours remaining before planned awakening. May increase to 10 mg if clinically indicated; maximum recommended dose is 10 mg once daily.
Concomitant use with weak CYP3A inhibitors: limit dose to 5 mg once daily.
Concomitant use with moderate or strong CYP3A inhibitors: avoid combination.
Concomitant use with moderate or strong CYP3A inducers: avoid combination.
Avoid taking with or immediately after a meal.
Schedule IV controlled substance (DEA) — assess abuse/misuse potential prior to and during treatment.

Narcolepsy — lemborexant antagonizes orexin/wake-promoting neurotransmission that narcolepsy patients depend upon.

CYP3A substrate: strong or moderate CYP3A inhibitors substantially increase lemborexant exposure — avoid concomitant use.
Weak CYP3A inhibitors: limit lemborexant dose to 5 mg.
Strong or moderate CYP3A inducers: substantially decrease lemborexant exposure and efficacy — avoid concomitant use.
CYP2B6 substrates: lemborexant may modestly induce CYP2B6; monitor for reduced efficacy of CYP2B6 substrate drugs.
Alcohol: additive CNS-depressant and psychomotor effects — avoid concomitant use.
Other CNS depressants (opioids, benzodiazepines, other hypnotics): additive sedation and impairment risk.

Somnolence — most common adverse reaction (~10% at 10 mg, ~7% at 5 mg, vs ~1% placebo).
Headache.
Abnormal dreams/nightmares.
Sleep paralysis (~1.6% at 10 mg dose).
Hypnagogic/hypnopompic hallucinations (~0.7% at 10 mg dose).
Next-day psychomotor and driving impairment, particularly at the 10 mg dose.
Complex sleep behaviors (sleepwalking, sleep-driving) have been reported; discontinue immediately if these occur (addressed in Warnings and Precautions, not a mandatory class boxed warning as with the Z-drugs).
Worsening depression and/or suicidal ideation — incidence numerically higher than placebo in trials (0.3% at 10 mg, 0.4% at 5 mg vs 0.2% placebo).
Discontinuation due to adverse reactions: ~2.6% (10 mg) and ~1.4% (5 mg).
Physical and psychological dependence potential (Schedule IV).

Assess sleep opportunity (need ≥7 hours before planned awakening) prior to dosing.
Monitor for next-day somnolence and psychomotor/driving impairment, especially at the 10 mg dose.
Monitor for complex sleep behaviors and instruct patients/caregivers to report these immediately; discontinue if they occur.
Monitor mood and for emergent or worsening depression/suicidal ideation; prescribe the lowest feasible tablet quantity in patients at risk for intentional overdose.
Assess for sleep paralysis and hallucinations at sleep-wake transitions.
Use caution and monitor respiratory status in patients with mild OSA or mild-moderate COPD; not studied in moderate-to-severe OSA or COPD.
Screen for CNS depressant polypharmacy and alcohol use.
Assess for signs of misuse, abuse, or dependence given Schedule IV status.

Pregnancy: No adequate human pregnancy data are available. Animal studies showed developmental toxicity only at high multiples of the maximum recommended human dose. A pregnancy exposure registry is available (1-888-274-2378).
Lactation: Presence in human milk has not been established but is likely given pharmacologic properties. Monitor breastfed infants for excessive sedation.