Lemborexant

Lemborexant
Clinical data
Trade names	Dayvigo
Other names	E-2006
License data	US DailyMed: Lemborexant;
Pregnancy; category	AU: B3; ;
Routes of; administration	By mouth
Drug class	Orexin antagonist
ATC code	N05CM21 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only) ; US: Schedule IV ;
Pharmacokinetic data
Protein binding	94%
Metabolism	Liver (major: CYP3A4, minor: CYP3A5)
Metabolites	M10
Elimination half-life	17–19 hours
Excretion	Feces: 57.4%; Urine: 29.1%
Identifiers
	IUPAC name (1R,2S)-2-[(2,4-Dimethylpyrimidin-5-yl)oxymethyl]-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropane-1-carboxamide;
CAS Number	1369764-02-2;
PubChem CID	56944144;
DrugBank	DB11951;
ChemSpider	34500836;
UNII	0K5743G68X;
KEGG	D11022;
ChEMBL	ChEMBL3545367;
Chemical and physical data
Formula	C22H20F2N4O2
Molar mass	410.425 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=NC(=NC=C1OCC2(CC2C(=O)NC3=NC=C(C=C3)F)C4=CC(=CC=C4)F)C;
	InChI InChI=1S/C22H20F2N4O2/c1-13-19(11-25-14(2)27-13)30-12-22(15-4-3-5-16(23)8-15)9-18(22)21(29)28-20-7-6-17(24)10-26-20/h3-8,10-11,18H,9,12H2,1-2H3,(H,26,28,29)/t18-,22+/m0/s1; Key:MUGXRYIUWFITCP-PGRDOPGGSA-N;

Lemborexant, sold under the brand name Dayvigo, is a medication for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults.^[2]^[3] Lemborexant was approved in the United States for use by adults with insomnia in December 2019.^[4]^[5]^[3]

Medical uses[]

Lemborexant is used in the treatment of insomnia.^[2] When compared to benzodiazepines there is a low risk of developing tolerance and dependence. ^[6] Memory and attention are not affected the next morning when taking this medication. ^[7]

Pharmacology[]

Pharmacodynamics[]

Lemborexant is a dual antagonist of the orexin OX₁ and OX₂ receptors.^[8]^[9]^[10]

Pharmacokinetics[]

The time to peak levels of lemborexant is 1 to 3 hours.^[2] A high-fat and high-calorie meal has been found to delay the time to peak levels by 2 hours.^[2] Its plasma protein binding in vitro is 94%.^[2] Lemborexant is metabolized primarily by CYP3A4 and to a lesser extent by CYP3A5.^[2] The elimination half-life of lemborexant is 17 to 19 hours.^[2] The medication is excreted in feces (57%) and to a lesser extent urine (29%).^[2]

History[]

In June 2016, Eisai initiated Phase III clinical trials in the United States, France, Germany, Italy, Japan, Poland, Spain and the UK.^[11]

In December 2019, lemborexant was approved for use in the United States based on results from the SUNRISE 1 and SUNRISE 2 Phase III clinical trials.^[3]^[12]

Society and culture[]

Generic names[]

Lemborexant is the generic name of the drug and its INN.

Brand names[]

Lemborexant is sold under the brand name Dayvigo.^[2]

References[]

^ ^a ^b "Dayvigo". Therapeutic Goods Administration (TGA). 23 July 2021. Retrieved 5 September 2021.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p "Dayvigo- lemborexant tablet, film coated". DailyMed. Retrieved 17 June 2021.
^ ^a ^b ^c "FDA Approves Dayvigo (lemborexant) for the Treatment of Insomnia in Adult Patients". Drugs.com. 23 December 2019. Retrieved 10 January 2020.
^ "Novel Drug Approvals for 2019". U.S. Food and Drug Administration (FDA). 2 January 2020. Retrieved 10 January 2020. This article incorporates text from this source, which is in the public domain.
^ "FDA-Approved Drugs: Lemborexant". U.S. Food and Drug Administration (FDA). Retrieved 10 January 2020.
^ Suzuki H, Hibino H (18 August 2021). "The effect of lemborexant for insomnia disorder". SAGE Open Medicine. 9: 20503121211039098. doi:10.1177/20503121211039098. ISSN 2050-3121. PMC 8377315. PMID 34422270.
^ Murphy P, Kumar D, Zammit G, Rosenberg R, Moline M (May 2020). "Safety of lemborexant versus placebo and zolpidem: effects on auditory awakening threshold, postural stability, and cognitive performance in healthy older participants in the middle of the night and upon morning awakening". Journal of Clinical Sleep Medicine. 16 (5): 765–773. doi:10.5664/jcsm.8294. PMC 7849806. PMID 32022664.
^ Christopher JA (2014). "Small-molecule antagonists of the orexin receptors". Pharmaceutical Patent Analyst. 3 (6): 625–638. doi:10.4155/ppa.14.46. PMID 25489915.
^ Boss C, Roch C (August 2015). "Recent trends in orexin research--2010 to 2015". Bioorganic & Medicinal Chemistry Letters. 25 (15): 2875–2887. doi:10.1016/j.bmcl.2015.05.012. PMID 26045032.
^ Boss C (December 2014). "Orexin receptor antagonists--a patent review (2010 to August 2014)". Expert Opinion on Therapeutic Patents. 24 (12): 1367–1381. doi:10.1517/13543776.2014.978859. PMID 25407283. S2CID 21106711.
^ "Lemborexant". Specialist Pharmacy Service. Archived from the original on 7 November 2017. Retrieved 5 November 2017.
^ "Drug Trials Snapshot: Dayvigo". U.S. Food and Drug Administration (FDA). 20 December 2019. Retrieved 24 January 2020. This article incorporates text from this source, which is in the public domain.

External links[]

"Lemborexant". Drug Information Portal. U.S. National Library of Medicine.

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[Dayvigo_APM_summary-1] "Dayvigo". Therapeutic Goods Administration (TGA). 23 July 2021. Retrieved 5 September 2021.

[Dayvigo_FDA_label-2] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p "Dayvigo- lemborexant tablet, film coated". DailyMed. Retrieved 17 June 2021.

[Approval-3] "FDA Approves Dayvigo (lemborexant) for the Treatment of Insomnia in Adult Patients". Drugs.com. 23 December 2019. Retrieved 10 January 2020.

[4] "Novel Drug Approvals for 2019". U.S. Food and Drug Administration (FDA). 2 January 2020. Retrieved 10 January 2020. This article incorporates text from this source, which is in the public domain.

[5] "FDA-Approved Drugs: Lemborexant". U.S. Food and Drug Administration (FDA). Retrieved 10 January 2020.

[6] Suzuki H, Hibino H (18 August 2021). "The effect of lemborexant for insomnia disorder". SAGE Open Medicine. 9: 20503121211039098. doi:10.1177/20503121211039098. ISSN 2050-3121. PMC 8377315. PMID 34422270.

[7] Murphy P, Kumar D, Zammit G, Rosenberg R, Moline M (May 2020). "Safety of lemborexant versus placebo and zolpidem: effects on auditory awakening threshold, postural stability, and cognitive performance in healthy older participants in the middle of the night and upon morning awakening". Journal of Clinical Sleep Medicine. 16 (5): 765–773. doi:10.5664/jcsm.8294. PMC 7849806. PMID 32022664.

[Christopher2014-8] Christopher JA (2014). "Small-molecule antagonists of the orexin receptors". Pharmaceutical Patent Analyst. 3 (6): 625–638. doi:10.4155/ppa.14.46. PMID 25489915.

[Boss2015-9] Boss C, Roch C (August 2015). "Recent trends in orexin research--2010 to 2015". Bioorganic & Medicinal Chemistry Letters. 25 (15): 2875–2887. doi:10.1016/j.bmcl.2015.05.012. PMID 26045032.

[Boss2014-10] Boss C (December 2014). "Orexin receptor antagonists--a patent review (2010 to August 2014)". Expert Opinion on Therapeutic Patents. 24 (12): 1367–1381. doi:10.1517/13543776.2014.978859. PMID 25407283. S2CID 21106711.

[11] "Lemborexant". Specialist Pharmacy Service. Archived from the original on 7 November 2017. Retrieved 5 November 2017.

[FDA_Snapshot-12] "Drug Trials Snapshot: Dayvigo". U.S. Food and Drug Administration (FDA). 20 December 2019. Retrieved 24 January 2020. This article incorporates text from this source, which is in the public domain.

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v t Insomnia pharmacotherapies
GABA_AR PAMs	Benzodiazepines: Brotizolam Cinolazepam Climazolam Clorazepate Doxefazepam Estazolam Etizolam Flunitrazepam Flurazepam Flutoprazepam Haloxazolam Loprazolam Lormetazepam Midazolam Nimetazepam Nitrazepam Quazepam Temazepam Triazolam; Nonbenzodiazepines/Z-drugs: Eszopiclone Zaleplon Zolpidem Zopiclone; Others: Alcohols (e.g., ethchlorvynol, amylene hydrate, ethanol) Barbiturates (e.g., amobarbital, pentobarbital, phenobarbital, secobarbital) Bromides (e.g., potassium bromide, sodium bromide) Carbamates (e.g., meprobamate) Chloral hydrate Clomethiazole Kava Paraldehyde Piperidinediones (e.g., glutethimide) Quinazolinones (e.g., methaqualone) Sulfonmethane Valerian
Antihistamines (H₁R inverse agonists)	Alimemazine Captodiame Dimenhydrinate Diphenhydramine Doxylamine Etodroxizine Hydroxyzine Meclizine Methapyrilene Pheniramine Phenyltoloxamine Pimethixene Promethazine Propiomazine Pyrilamine TCAs (e.g., amitriptyline, doxepin, trimipramine) TeCAs (e.g., mirtazapine) Triprolidine
OXR antagonists	Daridorexant Lemborexant Suvorexant
MTR agonists	Agomelatine Melatonin Ramelteon Tasimelteon
Miscellaneous	Antipsychotics (e.g., quetiapine, olanzapine, chlorpromazine) Ashwagandha Benzoctamine Cannabinoids (e.g., cannabis, dronabinol (THC), nabilone) Chamomile Fenadiazole Gabapentinoids (e.g., gabapentin, pregabalin, phenibut) Hops Lavender Menthyl isovalerate Niaprazine Opioids (e.g., hydrocodone, oxycodone, morphine) Passion flower Scopolamine Serotonin precursors (tryptophan, 5-HTP) Sodium oxybate (GHB) Sympatholytics (e.g., clonidine, guanfacine) TCAs (e.g., amitriptyline, doxepin, trimipramine) TeCAs (e.g., mirtazapine) Theanine Trazodone Valnoctamide

v t Orexin receptor modulators
OX₁	Agonists: Orexin (A, B) Antagonists: ACT-335827 ACT-462206 Almorexant Daridorexant Filorexant GSK-649868 (SB-649868) Lemborexant RTIOX-276 SB-334867 SB-408124 Suvorexant Vornorexant (ORN-0829, TS-142)
OX₂	Agonists: Danavorexton (TAK-925) Firazorexton Orexin (A, B) Suntinorexton TAK-994 Antagonists: ACT-335827 ACT-462206 Almorexant EMPA Filorexant GSK-649868 (SB-649868) JNJ-10397049 Lemborexant Seltorexant Suvorexant TCS-OX2-29 Vornorexant (ORN-0829, TS-142)