(1)valproic acid will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.velpatasvirMonitor Closely (1)lemborexant will decrease the level or effect of velpatasvir by affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Monitor CYP2B6 substrate for adequate clinical response. Consider increasing the CYP2B6 substrate dose according to specific prescribing recommendations.venlafaxineMonitor Closely (1)lemborexant, venlafaxine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.verapamilSerious - Use Alternative (1)verapamil will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lemborexant with moderate or strong CYP3A inhibitors.vigabatrinMonitor Closely (1)lemborexant will increase the level or effect of vigabatrin by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.vilazodoneMonitor Closely (1)lemborexant, vilazodone. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.vinblastineMonitor Closely (1)vinblastine will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.vincristineMonitor Closely (1)vincristine will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.vincristine liposomalMonitor Closely (1)vincristine liposomal will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.vinorelbineMonitor Closely (1)vinorelbine will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.voriconazoleSerious - Use Alternative (1)voriconazole will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lemborexant with moderate or strong CYP3A inhibitors.voxelotorSerious - Use Alternative (1)voxelotor will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lemborexant with moderate or strong CYP3A inhibitors.zafirlukastMonitor Closely (1)zafirlukast will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.zaleplonSerious - Use Alternative (1)lemborexant, zaleplon. Either increases effects of the other by sedation. Avoid or Use Alternate Drug. Use of lemborexant with other drugs to treat insomnia is not recommended.ziconotideMonitor Closely (1)lemborexant will increase the level or effect of ziconotide by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.zileutonMonitor Closely (1)zileuton will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.ziprasidoneMonitor Closely (2)ziprasidone will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification. lemborexant, ziprasidone. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.zolpidemSerious - Use Alternative (1)lemborexant, zolpidem. Either increases effects of the other by sedation. Avoid or Use Alternate Drug. Use of lemborexant with other drugs to treat insomnia is not recommended. 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%) Contraindications Narcolepsy Cautions CNS depression and daytime impairment 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, hypnagogic/hypnopompic hallucinations, cataplexy-like symptoms 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 Complex sleep behaviors, including sleepwalking, 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 Events can occur in hypnotic-naïve as well as in hypnotic-experienced persons Patients usually do not remember these events Complex sleep behaviors may occur following the first or any subsequent use of lemborexant, with or without concomitant use of alcohol and other CNS depressants Discontinue immediately if patient experiences a complex sleep behavior Compromised respiratory function Studied in mild to severe obstructive sleep apnea (OSA) and moderate-to-severe chronic obstructive pulmonary disease (COPD) in short-term clinical trials Studies have shown that clinically meaningful respiratory effects in patients with compromised respiratory function cannot be excluded; consider effect on respiratory function if prescribed to patients with compromised respiratory function; not studied in COPD patients with FEV1 <30% predicted Worsening depression/suicidal ideation 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 Comorbid diagnoses Evaluate for comorbid diagnoses where insomnia may be presenting manifestation of a medial and/or psychiatric disorder Failure of insomnia to remit after 7-10 days of treatment may indicate presence of a primary psychiatric and/or medical illness that should be evaluated Worsening of insomnia or emergence of new cognitive or behavioral abnormalities may be result of an unrecognized underlying psychiatric or medical disorder Drug interaction overview CNS depressants Avoid coadministration Coadministration with other CNS depressants (eg, benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression, which can cause daytime impairment Coadministration with alcohol increases lemborexant peak plasma concentration and AUC and produced a numerically greater negative impact on postural stability and memory as compared with alcohol alone Strong or moderate CYP3A inhibitors Avoid coadministration Coadministration with a strong or moderate CYP3A inhibitor increases lemborexant AUC and peak plasma concentration which may increase the risk of lemborexant adverse reactions Weak CYP3A inhibitors Modify lemborexant dose Do not exceed 5 mg/night if coadministered with weak CYP3A inhibitors (eg, chlorzoxazone, ranitidine) CYP3A inducers Avoid coadministration Concomitant use with a strong or moderate CYP3A inducer decreases lemborexant exposure, which may reduce lemborexant efficacy CYP2B6 substrates Consider increasing CYP2B6 substrate dose as recommended in prescribing information Coadministration decreases AUC of CYP2B6 substrates Check prescribing information for CYP2B6 substrate for dosage recommendations if coadministered 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 Clinicians are encouraged to register patients in the Dayvigo pregnancy registry by calling 1-888-274-2378 Animal studies Rats Lemborexant was administered orally to pregnant rats during organogenesis in 2 studies at doses of 60, 200, and 600 mg/kg/day or 20, 60, and 200 mg/kg/day, which are approximately 6 to >300 times the maximum recommended human dose (MRHD) based on AUC Lemborexant caused maternal toxicity, manifested by decreased body weight and food consumption, decreased mean fetal body weight, an increased number of dead fetuses, and skeletal, external, and visceral malformations (omphalocele, cleft palate, and membranous ventricular septal defect) at >300 times the MRHD based on AUC Lemborexant was administered orally to pregnant rats during pregnancy and lactation at doses of 30, 100, and 300 mg/kg/day, which are approximately 15-206 times the MRHD based on AUC Lemborexant caused maternal toxicity that consisted of decreased body weight and food consumption and toxicity to offspring consisting of decreased pup body weights, decreased femur length, and decreased acoustic startle responses at 206 times the MRHD based on AUC Rabbits Lemborexant was administered orally to pregnant rabbits during the period of organogenesis at doses of 10, 30, and 100 mg/kg/day, which are approximately 7-139 times the MRHD based on AUC Lemborexant caused maternal toxicity that consisted of decreased body weight and food consumption and a higher incidence of skeletal variations (presence of cervical ribs and supernumerary lung lobes) at approximately 139 times the MRHD based on AUC Lactation Lactation Available data from a lactation study in 8 women indicates that the drug is transferred into the breastmilk of nursing mothers; results have established a mean daily infant dose of 0.0029 mg/kg/day and a relative infant dose of less than 2% of the maternal dose; These data support that transfer of this drug into breastmilk is low There are no data on effects of this drug on breastfed infant, or effects on milk production; monitor infants exposed through breastmilk 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 conditionPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. 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 Absorption Peak plasma concentration: 1-3 hr Food (high-fat, high-calorie meal) decreases peak plasma concentration by 23%, AUC by 18%, and delays peak plasma time by 2 hr Distribution Protein bound: ~94% Vd: 1970 L Blood-plasma ratio: 0.65 Metabolism CYP3A4 (primary); CYP3A5 (less extent) Major circulating metabolite: M10 Elimination Half-life: 17 hr (5 mg); 19 hr (10 mg) Excretion: Feces 29.1%; urine <1% Oral 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 Storage Store at controlled room temperature of 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF) No images available for this drug. No images available for this drug.A Patient Handout is not currently available for this monograph.Print FormularyPatient DiscountsAdding plans allows you to compare formulary status to other drugs in the same class.To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.Create Your List of PlansAdding plans allows you to:View the formulary and any restrictions for each plan.Manage and view all your plans together – even plans in different states.Compare formulary status to other drugs in the same class.Access your plan list on any device – mobile or desktop. The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information. View explanations for tiers and restrictions Tier Description 1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs. 2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs. 3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs. 4 This drug is