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Lemborexant: Drug information

Lemborexant: Drug information
(For additional information see "Lemborexant: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • DayVigo
Brand Names: Canada
  • DayVigo
Pharmacologic Category
  • Hypnotic, Miscellaneous;
  • Orexin Receptor Antagonist
Dosing: Adult

Note: Intended for short-term use (≤4 to 8 weeks), preferably in conjunction with nonpharmacologic therapies (ACP [Qaseem 2016]; ESRS [Riemann 2017]; Winkelman 2021). Limit long-term use to cases for which nonpharmacologic treatments are not available or not effective and benefits are felt to outweigh risks (AASM [Sateia 2017]).

Insomnia, sleep onset or sleep maintenance : Oral: 5 mg once daily, as needed, at bedtime with at least 7 hours before planned time of awakening; may increase to 10 mg based on response and tolerability; maximum dose: 10 mg/day.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Mild and moderate impairment: No dosage adjustment necessary.

Severe impairment: No dosage adjustment necessary; however, patients may have an increased risk of somnolence due to increased exposure to lemborexant.

Dosing: Hepatic Impairment: Adult

Mild impairment: No dosage adjustment necessary.

Moderate impairment: Maximum dose: 5 mg/day.

Severe impairment: Use is not recommended (has not been studied).

Dosing: Older Adult

Refer to adult dosing; use caution with doses >5 mg.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

DayVigo: 5 mg, 10 mg

Generic Equivalent Available: US

No

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

DayVigo: 5 mg, 10 mg

Controlled Substance

C-IV

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212028s000lbl.pdf#page=21, must be dispensed with this medication.

Administration: Adult

Oral: Administer at bedtime with at least 7 hours before planned time of awakening. Time to sleep onset may be delayed if taken with or soon after a meal.

Use: Labeled Indications

Insomnia, sleep onset or sleep maintenance: Treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults.

Medication Safety Issues
Sound-alike/look-alike issues:

Dayvigo may be confused with Daypro, Daysee, or Daytrana.

Adverse Reactions (Significant): Considerations
CNS depression/falls

Lemborexant is frequently associated with central nervous system depression or next-day drowsiness, which may impair physical or mental abilities and increase the risk of falling, particularly in older adults. Balance impairment during the night has also been observed. Some patients experienced next-morning driving ability impairment with the 10 mg dose, indicating there is individual variation in sensitivity to CNS depressant effects (Ref).

Mechanism: Dose-related; related to the pharmacologic action via orexin receptor antagonism which is believed to suppress wake drive.

Onset: Rapid; sleep onset occurs within ~15 to 20 minutes; in older adults ≥55 years of age, onset of sleep occurs within 23 to 28 minutes (Ref). CNS depressant effects may persist for up to several days after discontinuing use.

Risk factors:

• Daytime impairment is increased with less than a full night of sleep (ie, <7 hours)

• Higher than recommended doses

• Concomitant use with other CNS depressants (eg, benzodiazepines, alcohol)

• Older adults (risk of falling)

Complex sleep behaviors

Events associated with complex sleep-related disorder, including hazardous sleep-related activities such as sleep-walking, sleep-driving, cooking and eating food, making phone calls, or having sex while asleep have been observed rarely with lemborexant at therapeutic doses, with or without concomitant use of alcohol or other CNS depressants. Patients usually do not remember these events.

Onset: Varied; may occur at any time (following the first dose or any subsequent dose).

Sleep-related effects

Lemborexant may cause abnormal dreams or nightmares infrequently and may lead to nonadherence or discontinuation. In addition, sleep paralysis (inability to move or speak for up to several minutes during sleep-wake transitions), hypnogenic hallucinations/hypnopompic hallucinations, or mild cataplexy may also occur. Cataplexy-like symptoms may occur during the night or day and are not always associated with a triggering event (eg, laughter, surprise).

Mechanism: Unknown whether these events are specifically related to antagonism of orexin receptors; however, orexin neuron loss is associated with the symptoms of narcolepsy which suggests orexin receptor antagonists can theoretically produce narcolepsy symptoms, particularly cataplexy (Ref).

Onset: Sleep paralysis events typically occurred following the first 1 or 2 doses and occurred around the time of sleep onset (within 1 hour of the dose). Two reports of cataplexy occurred ~14 hours postdose and lasted 3 to 4 minutes (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

1% to 10%: Nervous system: Abnormal dreams (≤2%) (table 1), drowsiness (7% to 10%) (table 2), fatigue (7% to 10%) (table 3), headache (5% to 6%), nightmares (≤2%) (table 4), sleep paralysis (1% to 2%) (table 5)

Lemborexant: Adverse Reaction: Abnormal Dreams

Drug (Lemborexant)

Placebo

Dose

Number of Patients (Lemborexant)

Number of Patients (Placebo)

2%

0.9%

10 mg

582

528

0.9%

0.9%

5 mg

580

528

Lemborexant: Adverse Reaction: Drowsiness

Drug (Lemborexant)

Placebo

Dose

Number of Patients (Lemborexant)

Number of Patients (Placebo)

10%

1%

10 mg

582

528

7%

1%

5 mg

580

528

Lemborexant: Adverse Reaction: Fatigue

Drug (Lemborexant)

Placebo

Dose

Number of Patients (Lemborexant)

Number of Patients (Placebo)

10%

1%

10 mg

582

528

7%

1%

5 mg

580

528

Lemborexant: Adverse Reaction: Nightmares

Drug (Lemborexant)

Placebo

Dose

Number of Patients (Lemborexant)

Number of Patients (Placebo)

2%

0.9%

10 mg

582

528

0.9%

0.9%

5 mg

580

528

Lemborexant: Adverse Reaction: Sleep Paralysis

Drug (Lemborexant)

Placebo

Dose

Number of Patients (Lemborexant)

Number of Patients (Placebo)

2%

0%

10 mg

582

528

1%

0%

5 mg

580

528

<1%: Nervous system: Complex sleep-related disorder (Scott 2020), hypnogenic hallucinations

Lemborexant: Adverse Reaction: Hypnogenic Hallucinations

Drug (Lemborexant)

Placebo

Dose

Number of Patients (Lemborexant)

Number of Patients (Placebo)

0.7%

0%

10 mg

582

528

0.1%

0%

5 mg

580

528

Frequency not defined:

Cardiovascular: Palpitations

Nervous system: Cataplexy

Contraindications

Narcolepsy.

Warnings/Precautions

Disease-related concerns:

• Depression: Use with caution in patients with depression; worsening of depression, including suicide or suicidal ideation, has been reported with the use of hypnotics. Intentional overdose may be an issue in this population. The minimum dose that will effectively treat the individual patient should be used. Prescriptions should be written for the smallest quantity consistent with good patient care.

• Drug abuse: Use with caution in patients with a history of drug abuse or dependence.

• Hepatic impairment: Use is not recommended in patients with severe hepatic impairment (has not been studied).

• Respiratory disease: Use with caution in patients with respiratory compromise, chronic obstructive pulmonary disease, or sleep apnea.

Other warnings/precautions:

• Appropriate use: Symptomatic treatment of insomnia should be initiated only after careful evaluation of potential causes of sleep disturbance. Failure of sleep disturbance to resolve after 7 to 10 days may indicate psychiatric and/or medical illness.

Metabolism/Transport Effects

Substrate of CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces CYP2B6 (weak)

Drug Interactions

Alcohol (Ethyl): May enhance the CNS depressant effect of Lemborexant. Alcohol (Ethyl) may increase the serum concentration of Lemborexant. Risk X: Avoid combination

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification

BuPROPion: CYP2B6 Inducers (Weak) may decrease the serum concentration of BuPROPion. Risk C: Monitor therapy

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CNS Depressants: Lemborexant may enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Lemborexant. Risk X: Avoid combination

CYP3A4 Inducers (Strong): May decrease the serum concentration of Lemborexant. Risk X: Avoid combination

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Lemborexant. Risk X: Avoid combination

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Lemborexant. Risk X: Avoid combination

CYP3A4 Inhibitors (Weak): May increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider therapy modification

Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Melatonin: May enhance the sedative effect of Hypnotics (Nonbenzodiazepine). Risk C: Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Oxybate Salt Products: Hypnotics (Nonbenzodiazepine) may enhance the CNS depressant effect of Oxybate Salt Products. Risk X: Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Spironolactone: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Treosulfan: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination

Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

Food Interactions

Concomitant alcohol use increases the risk of CNS depression, daytime impairment, postural instability, and memory impairment. Management: Avoid alcohol consumption with lemborexant.

Pregnancy Considerations

Adverse events were observed in some animal reproduction studies.

Data collection to monitor pregnancy and infant outcomes following exposure to lemborexant is ongoing. Health care providers are encouraged to enroll females exposed to lemborexant during pregnancy in the Dayvigo Pregnancy Registry (888-274-2378).

Breastfeeding Considerations

It is not known if lemborexant is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Breastfeeding infants should be monitored for excessive sedation.

Monitoring Parameters

Hepatic and renal function (baseline and as clinically indicated); worsening depression or suicidality; mental alertness.

Mechanism of Action

Lemborexant blocks the binding of wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R, which is thought to suppress wake drive.

Pharmacokinetics

Onset: ~15 to 20 minutes.

Absorption: High-fat and high-calorie meals decrease the Cmax by 23%, increase the AUC0-∞ by 18%, and delay the Tmax by 2 hours.

Distribution: Vd: 1,970 L.

Protein binding: ~94% in vitro.

Metabolism: Hepatic metabolism primarily by CYP3A4, and to a lesser extent by CYP3A5; the major circulating active metabolite is M10.

Half-life elimination: 17 to 19 hours.

Time to peak: ~1 to 3 hours.

Excretion: Feces: 57.4%; urine: 29.1% (<1% as unchanged drug).

Pharmacokinetics: Additional Considerations

Renal function impairment: Lemborexant exposure (AUC) was increased in patients with severe renal impairment (Child-Pugh class C).

Hepatic function impairment: Lemborexant exposure (AUC) was increased in patients with mild and moderate hepatic impairment (Child-Pugh class A and B), and the terminal half-life was increased in patients with moderate hepatic impairment (Child-Pugh class B).

Pricing: US

Tablets (DayVigo Oral)

5 mg (per each): $11.77

10 mg (per each): $11.77

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Dayvigo (AU, HK, ID, IN, JP, KR)


For country abbreviations used in Lexicomp (show table)

REFERENCES

  1. Dayvigo (lemborexant) [prescribing information]. Woodcliff Lake, NJ: Eisai Inc; March 2021.
  2. Herring WJ, Roth T, Krystal AD, Michelson D. Orexin receptor antagonists for the treatment of insomnia and potential treatment of other neuropsychiatric indications. J Sleep Res. 2019;28(2):e12782. doi:10.1111/jsr.12782 [PubMed 30338596]
  3. Murphy P, Moline M, Mayleben D, et al. Lemborexant, a dual orexin receptor antagonist (DORA) for the treatment of insomnia disorder: results from a bayesian, adaptive, randomized, double-blind, placebo-controlled study. J Clin Sleep Med. 2017;13(11):1289-1299. doi:10.5664/jcsm.6800 [PubMed 29065953]
  4. Qaseem A, Kansagara D, Forciea MA, Cooke M, Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Management of chronic insomnia disorder in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2016;165(2):125-133. doi:10.7326/M15-2175 [PubMed 27136449]
  5. Riemann D, Baglioni C, Bassetti C, et al. European guideline for the diagnosis and treatment of insomnia. J Sleep Res. 2017;26(6):675-700. doi:10.1111/jsr.12594 [PubMed 28875581]
  6. Rosenberg R, Murphy P, Zammit G, et al. Comparison of lemborexant with placebo and zolpidem tartrate extended release for the treatment of older adults with insomnia disorder: a phase 3 randomized clinical trial [published correction appears in JAMA Netw Open. 2020;3(4):e206497]. JAMA Netw Open. 2019;2(12):e1918254. doi:10.1001/jamanetworkopen.2019.18254 [PubMed 31880796]
  7. Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017;13(2):307-349. doi:10.5664/jcsm.6470 [PubMed 27998379]
  8. Scott LJ. Lemborexant: first approval. Drugs. 2020;80(4):425-432. doi:10.1007/s40265-020-01276-1 [PubMed 32096020]
  9. Winkelman JW. Overview of the treatment of insomnia in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 10, 2021.
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