Lemborexant

Indications

Lemborexant is used for: Insomnia

Adult Dose

Insomnia Indicated for insomnia characterized by difficulties with sleep onset and/or sleep maintenance 5 mg PO no more than once per night, immediately before going to bed, with at least 7 hr remaining before planned time of awakening May increase dose to maximum of 10 mg based on clinical response and tolerability Hepatic impairment Mild (Child-Pugh A): No dose adjustment recommended; however, patients may experience an increased risk of somnolence; AUC increased Moderate (Child-Pugh B): Not to exceed 5 mg/night; AUC, peak plasma concentration, and half-life increased Severe (Child-Pugh C): Not recommended (not studied)

Child Dose

Renal Dose

Renal impairment Mild, moderate, or severe: No dose adjustment recommended Severe: AUC increased; patients may experience increased risk of somnolence

Administration

Time to sleep onset may be delayed if taken with or soon after a meal Take at least 7 hr before planned awakening Do not take more than 1 dose/night Avoid alcohol consumption

Contra Indications

Narcolepsy

Precautions

In primarily depressed patients treated with hypnotics, worsening of depression and suicidal thoughts and actions (including completed suicides) have been reported; monitor for new behavioral signs or symptoms CNS depressant that can impair daytime wakefulness even when used as prescribed; CNS depression may persist and affect next-day tasks (eg, driving ability); CNS depression may persist in some patients for several days after discontinuing; coadministration with other CNS depressants may increase risk Sleep paralysis, an inability to move or speak for up to several minutes during sleep-wake transitions, and hypnagogic/hypnopompic hallucinations, including vivid and disturbing perceptions, can occur; mild cataplexy can occur, with symptoms that include periods of leg weakness lasting from seconds to a few minutes Complex sleep behaviors, including sleep-walking, sleep-driving, and engaging in other activities while not fully awake (eg, preparing and eating food, making phone calls, having sex), reported with hypnotic use Consider effect on respiratory function if prescribed to patients with compromised respiratory function; has not been studied with moderate-to-severe obstructive sleep apnea or COPD

Pregnancy-Lactation

Pregnancy Data are not available on use in pregnant women to evaluate for drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes Lactation Data are not available on the presence of lemborexant in human milk, effects on breastfed infants, or effects on milk production Lemborexant and its metabolites are present in the milk of lactating rats; when a drug is present in animal milk, it is likely that the drug will be present in human milk Monitor infants exposed through breast milk for excessive sedation Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Interactions

CNS depressants Coadministration with other CNS depressants (eg, benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression, which can cause daytime impairment CYP3A inhibitors Coadministration with a strong, moderate, or weak CYP3A inhibitor increases lemborexant AUC and peak plasma concentration which may increase the risk of lemborexant adverse reactions CYP3A inducers Concomitant use with a strong or moderate CYP3A inducer decreases lemborexant exposure, which may reduce lemborexant efficacy CYP2B6 substrates Coadministration decreases AUC of CYP2B6 substrates Check prescribing information for CYP2B6 substrate for dosage recommendations if coadministered

Adverse Effects

Side effects of Lemborexant : 1-10% 5 mg/night Somnolence or fatigue (6.9%) Headache (5.9%) Sleep paralysis (1.3%) 10 mg/night Somnolence or fatigue (9.6%) Headache (4.5%) Nightmare or abnormal dreams (2.2%) Sleep paralysis (1.6%) <1% 5 mg/night Nightmare or abnormal dreams (0.9%) Hypnagogic hallucinations (0.1%) 10 mg/night Hypnagogic hallucinations (0.7%)

Mechanism of Action

Dual orexin antagonist (DORA) Orexins are neuropeptides that regulate the sleep-wake cycle; orexins promote wakefulness by binding G-protein-coupled receptors, OX1R and OX2R A major metabolite of lemborexant, M10, binds with comparable affinity as the parent drug to orexin receptors OX1R and OX2R