Synopsis
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1. (1r,2s)-2-(((2,4-dimethyl-5-pyrimidinyl)oxy)methyl)-2-(3-fluorophenyl)-n-(5-fluoro-2-pyridinyl)cyclopropanecarboxamide
2. Cyclopropanecarboxamide, 2-(((2,4-dimethyl-5-pyrimidinyl)oxy)methyl)-2-(3-fluorophenyl)-n-(5-fluoro-2-pyridinyl)-, (1r,2s)-
3. Dayvigo
1. 1369764-02-2
2. Dayvigo
3. E-2006
4. E2006
5. 0k5743g68x
6. (1r,2s)-2-[(2,4-dimethylpyrimidin-5-yl)oxymethyl]-2-(3-fluorophenyl)-n-(5-fluoropyridin-2-yl)cyclopropane-1-carboxamide
7. (1r,2s)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-2-(3-fluorophenyl)-n-(5-fluoropyridin-2-yl)cyclopropanecarboxamide
8. Cyclopropanecarboxamide, 2-(((2,4-dimethyl-5-pyrimidinyl)oxy)methyl)-2-(3-fluorophenyl)-n-(5-fluoro-2-pyridinyl)-, (1r,2s)-
9. (1~{r},2~{s})-2-[(2,4-dimethylpyrimidin-5-yl)oxymethyl]-~{n}-(5-fluoranylpyridin-2-yl)-2-(3-fluorophenyl)cyclopropane-1-carboxamide
10. E 2006
11. Lemborexant [usan:inn]
12. Unii-0k5743g68x
13. (1r,2s)-2-(((2,4-dimethyl-5-pyrimidinyl)oxy)methyl)-2-(3-fluorophenyl)-n-(5-fluoro-2-pyridinyl)cyclopropanecarboxamide
14. (1r,2s)-2-((2,4-dimethylpyrimidin-5-yl)oxymethyl)-2-(3-fluorophenyl)-n-(5-fluoropyridin-2-yl)cyclopropane-1-carboxamide
15. (1r,2s)-2-[[(2,4-dimethyl-5-pyrimidinyl)oxy]methyl]-2-(3-fluorophenyl)-n-(5-fluoro-2-pyridinyl)cyclopropanecarboxamide
16. Cyclopropanecarboxamide, 2-[[(2,4-dimethyl-5-pyrimidinyl)oxy]methyl]-2-(3-fluorophenyl)-n-(5-fluoro-2-pyridinyl)-, (1r,2s)-
17. Dayvigo (tn)
18. Lemborexant [inn]
19. Lemborexant(e2006)
20. Lemborexant [mi]
21. Lemborexant; E-2006
22. Lemborexant [jan]
23. Lemborexant [usan]
24. Lemborexant [who-dd]
25. Lemborexant (jan/usan/inn)
26. Gtpl9302
27. Schembl2116558
28. Chembl3545367
29. Lemborexant [orange Book]
30. Dtxsid401027940
31. Amy27888
32. Ex-a2337
33. Bdbm50093793
34. Zinc118073503
35. Db11951
36. Compound 34 [pmid: 25953512]
37. Ncgc00488783-01
38. Ac-30918
39. Hy-16725
40. J3.610.985h
41. D11022
42. E-2006e-2006
43. A886588
44. Q20707990
45. (1r,2s)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-n-(5-fluoropyridin-2-yl)cyclopropane-1-carboxamide
| Molecular Weight | 410.4 g/mol |
|---|---|
| Molecular Formula | C22H20F2N4O2 |
| XLogP3 | 3.2 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 6 |
| Exact Mass | 410.15543222 g/mol |
| Monoisotopic Mass | 410.15543222 g/mol |
| Topological Polar Surface Area | 77 Ų |
| Heavy Atom Count | 30 |
| Formal Charge | 0 |
| Complexity | 612 |
| Isotope Atom Count | 0 |
| Defined Atom Stereocenter Count | 2 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Covalently Bonded Unit Count | 1 |
Lemborexant is indicated for the treatment of adult patients with insomnia characterized by difficulties with sleep onset and/or sleep maintenance.
FDA Label
Lemborexant promotes sleep by antagonizing the actions of wake-promoting chemicals in the brain. Episodes of complex sleep behaviors (e.g. eating food, having sex, making phone calls) have been reported in patients using lemborexant - these events may occur in hypnotic-naive and hyponotic-experienced patients, and patients are unlikely to remember these events. Patients exhibiting complex sleep behaviors should discontinue lemborexant immediately. Lemborexant may carry some risk of abuse, and should be used with caution in patients with a history of alcohol or drug addiction. Its controlled substance schedule is currently under review by the Drug Enforcement Administration.
Orexin Receptor Antagonists
Substances that bind to and inhibit the action of OREXIN RECEPTORS. Drugs in this class have been used as SLEEP AIDS, PHARMACEUTICAL. (See all compounds classified as Orexin Receptor Antagonists.)
N - Nervous system
N05 - Psycholeptics
N05C - Hypnotics and sedatives
N05CM - Other hypnotics and sedatives
N05CM21 - Lemborexant
Absorption
Animal models of lemborexant disposition have demonstrated rapid absorption following oral administration. The Tmax of lemborexant is approximately 1-3 hours, or 3-5 hours following administration of a high-fat, high-calorie meal. Cmax and AUC0-24h increase at a rate slightly less than proportionate to the given dose. Following administration of a high-fat, high-calorie meal, Cmax is decreased by 23% and AUC0-inf is increased by 18%. AUC, Cmax, and terminal half-life are increased in the presence of moderate hepatic impairment, and AUC (but not half-life) is increased in the presence of mild hepatic impairment.
Route of Elimination
Following oral administration, 57.4% of the dose is found in the feces and 29.1% in the urine. Less than 1% of the dose recovered in the urine exists as unchanged parent drug, suggesting extensive metabolism.
Volume of Distribution
The volume of distribution of lemborexant is 1970 L, indicating extensive tissue distribution.
Given that less than 1% of an administered dose is recovered unchanged in the urine, it is likely that lemborexant is extensively metabolized - this has been confirmed in rat and monkey models, but its metabolism in humans has not been fully characterized. Prescribing information states that it is predominantly metabolized by CYP3A4, with a smaller contribution by CYP3A5. The major circulating metabolite is lemborexant's M10 metabolite, which is pharmacologically active and binds to orexin receptors with a similar affinity to the parent drug. The M10 metabolite has the potential to induce CYP3A and CYP2B6 enzymes, weakly inhibit CYP3A enzymes, and is a substrate of P-gp transporters.
The half-life for lemborexant at doses of 5mg and 10mg is 17 and 19 hours, respectively.
The orexin neuropeptide signaling system is involved in many physiologic functions, including sleep/wake control. Orexin-A and orexin-B activate post-synaptic G-protein coupled orexin-1 receptors (OX1R) and orexin-2 receptors (OX2R), which are found on neurons in the hypothalamus that project to numerous wake-controlling nuclei. Each receptor carries slightly different activity - activation of OX1R appears to suppress the onset of rapid eye movement (REM) sleep, whereas activation of OX2R appears to suppress non-REM sleep. Lemborexant is an competitive antagonist of OX1R and OX2R. By blocking the binding of wake-promoting orexin-A and -B at these receptors, lemborexant suppresses the wake-drive, thereby promoting sleep.
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FULL SCREEN VIEW Click here to open all results in a new tab [this preview display 10 results]Details:
Lemborexant is a Controlled Substance drug candidate, which is currently being evaluated in phase IV clinical studies for the treatment of Sleep Disorders, Circadian Rhythm.
Lead Product(s): Lemborexant,Inapplicable
Therapeutic Area: Sleep Brand Name: Undisclosed
Study Phase: Phase IVProduct Type: Controlled Substance
Sponsor: Eisai | Stanford University
Deal Size: Inapplicable Upfront Cash: Inapplicable
Deal Type: Inapplicable March 13, 2025

Lead Product(s) : Lemborexant,Inapplicable
Therapeutic Area : Sleep
Highest Development Status : Phase IV
Partner/Sponsor/Collaborator : Eisai | Stanford University
Deal Size : Inapplicable
Deal Type : Inapplicable
Lemborexant in Delayed Sleep Phase Syndrome
Details : Lemborexant is a Controlled Substance drug candidate, which is currently being evaluated in phase IV clinical studies for the treatment of Sleep Disorders, Circadian Rhythm.
Product Name : Undisclosed
Product Type : Controlled Substance
Upfront Cash : Inapplicable
March 13, 2025

Details:
Lemborexant is a Controlled Substance drug candidate, which is currently being evaluated in phase II clinical studies for the treatment of Depressive Disorder, Major.
Lead Product(s): Lemborexant,Inapplicable
Therapeutic Area: Psychiatry/Psychology Brand Name: Undisclosed
Study Phase: Phase IIProduct Type: Controlled Substance
Sponsor: University of Toronto | Centre for Addiction and Mental Health | Toronto Metropolitan University
Deal Size: Inapplicable Upfront Cash: Inapplicable
Deal Type: Inapplicable February 24, 2025

Lead Product(s) : Lemborexant,Inapplicable
Therapeutic Area : Psychiatry/Psychology
Highest Development Status : Phase II
Partner/Sponsor/Collaborator : University of Toronto | Centre for Addiction and Mental Health | Toronto Metropolitan University
Deal Size : Inapplicable
Deal Type : Inapplicable
Lemborexant for the Treatment of Residual Insomnia in Major Depressive Disorder (MDD)
Details : Lemborexant is a Controlled Substance drug candidate, which is currently being evaluated in phase II clinical studies for the treatment of Depressive Disorder, Major.
Product Name : Undisclosed
Product Type : Controlled Substance
Upfront Cash : Inapplicable
February 24, 2025

Details:
Lemborexant is a Controlled Substance drug candidate, which is currently being evaluated in clinical studies for the treatment of Sleep Initiation and Maintenance Disorders.
Lead Product(s): Lemborexant,Inapplicable
Therapeutic Area: Sleep Brand Name: Undisclosed
Study Phase: UndisclosedProduct Type: Controlled Substance
Sponsor: Toronto Metropolitan University | The Royal Ottawa Mental Health Centre
Deal Size: Inapplicable Upfront Cash: Inapplicable
Deal Type: Inapplicable January 16, 2025

Lead Product(s) : Lemborexant,Inapplicable
Therapeutic Area : Sleep
Highest Development Status : Undisclosed
Partner/Sponsor/Collaborator : Toronto Metropolitan University | The Royal Ottawa Mental Health Centre
Deal Size : Inapplicable
Deal Type : Inapplicable
Efficacy of CBT-I and Lemborexant Medication for Different Subtypes of Chronic Insomnia
Details : Lemborexant is a Controlled Substance drug candidate, which is currently being evaluated in clinical studies for the treatment of Sleep Initiation and Maintenance Disorders.
Product Name : Undisclosed
Product Type : Controlled Substance
Upfront Cash : Inapplicable
January 16, 2025

Details:
Lemborexant is a Controlled Substance drug candidate, which is currently being evaluated in phase II clinical studies for the treatment of Delirium.
Lead Product(s): Lemborexant,Inapplicable
Therapeutic Area: Neurology Brand Name: Undisclosed
Study Phase: Phase IIProduct Type: Controlled Substance
Sponsor: Eisai Inc | Providence Healthcare | St. Paul's Hospital, Vancouver
Deal Size: Inapplicable Upfront Cash: Inapplicable
Deal Type: Inapplicable October 18, 2024

Lead Product(s) : Lemborexant,Inapplicable
Therapeutic Area : Neurology
Highest Development Status : Phase II
Partner/Sponsor/Collaborator : Eisai Inc | Providence Healthcare | St. Paul's Hospital, Vancouver
Deal Size : Inapplicable
Deal Type : Inapplicable
Lemborexant to Prevent Post-operative Delirium in Cardiac Surgery Patients
Details : Lemborexant is a Controlled Substance drug candidate, which is currently being evaluated in phase II clinical studies for the treatment of Delirium.
Product Name : Undisclosed
Product Type : Controlled Substance
Upfront Cash : Inapplicable
October 18, 2024

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Details:
Lemborexant is a Controlled Substance drug candidate, which is currently being evaluated in phase II clinical studies for the treatment of Alzheimer Disease.
Lead Product(s): Lemborexant,Inapplicable
Therapeutic Area: Neurology Brand Name: Undisclosed
Study Phase: Phase IIProduct Type: Controlled Substance
Sponsor: National Institutes of Health | Eisai Inc | National Institute on Aging
Deal Size: Inapplicable Upfront Cash: Inapplicable
Deal Type: Inapplicable February 23, 2024

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Lead Product(s) : Lemborexant,Inapplicable
Therapeutic Area : Neurology
Highest Development Status : Phase II
Partner/Sponsor/Collaborator : National Institutes of Health | Eisai Inc | National Institute on Aging
Deal Size : Inapplicable
Deal Type : Inapplicable
DORA and LP in Alzheimer's Disease Biomarkers
Details : Lemborexant is a Controlled Substance drug candidate, which is currently being evaluated in phase II clinical studies for the treatment of Alzheimer Disease.
Product Name : Undisclosed
Product Type : Controlled Substance
Upfront Cash : Inapplicable
February 23, 2024

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Details:
Lemborexant is a Controlled Substance drug candidate, which is currently being evaluated in phase IV clinical studies for the treatment of Sleep Initiation and Maintenance Disorders.
Lead Product(s): Lemborexant,Inapplicable
Therapeutic Area: Sleep Brand Name: Undisclosed
Study Phase: Phase IVProduct Type: Controlled Substance
Sponsor: Undisclosed
Deal Size: Inapplicable Upfront Cash: Inapplicable
Deal Type: Inapplicable October 23, 2023

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Lead Product(s) : Lemborexant,Inapplicable
Therapeutic Area : Sleep
Highest Development Status : Phase IV
Partner/Sponsor/Collaborator : Undisclosed
Deal Size : Inapplicable
Deal Type : Inapplicable
Lemborexant for Insomnia in a Patient With Dementia: An N-of-1 Trial
Details : Lemborexant is a Controlled Substance drug candidate, which is currently being evaluated in phase IV clinical studies for the treatment of Sleep Initiation and Maintenance Disorders.
Product Name : Undisclosed
Product Type : Controlled Substance
Upfront Cash : Inapplicable
October 23, 2023

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Details:
Lemborexant is a Controlled Substance drug candidate, which is currently being evaluated in phase II clinical studies for the treatment of Alzheimer Disease.
Lead Product(s): Lemborexant,Inapplicable
Therapeutic Area: Neurology Brand Name: Undisclosed
Study Phase: Phase IIProduct Type: Controlled Substance
Sponsor: Brendan Lucey
Deal Size: Inapplicable Upfront Cash: Inapplicable
Deal Type: Inapplicable February 15, 2023

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Lead Product(s) : Lemborexant,Inapplicable
Therapeutic Area : Neurology
Highest Development Status : Phase II
Partner/Sponsor/Collaborator : Brendan Lucey
Deal Size : Inapplicable
Deal Type : Inapplicable
Acute Effect of Lemborexant on CSF Amyloid-Beta and Tau
Details : Lemborexant is a Controlled Substance drug candidate, which is currently being evaluated in phase II clinical studies for the treatment of Alzheimer Disease.
Product Name : Undisclosed
Product Type : Controlled Substance
Upfront Cash : Inapplicable
February 15, 2023

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Details:
Lemborexant is a Controlled Substance drug candidate, which is currently being evaluated in phase II clinical studies for the treatment of Sleep Initiation and Maintenance Disorders.
Lead Product(s): Lemborexant,Inapplicable
Therapeutic Area: Sleep Brand Name: Undisclosed
Study Phase: Phase IIProduct Type: Controlled Substance
Sponsor: Undisclosed
Deal Size: Inapplicable Upfront Cash: Inapplicable
Deal Type: Inapplicable October 26, 2022

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Lead Product(s) : Lemborexant,Inapplicable
Therapeutic Area : Sleep
Highest Development Status : Phase II
Partner/Sponsor/Collaborator : Undisclosed
Deal Size : Inapplicable
Deal Type : Inapplicable
Details : Lemborexant is a Controlled Substance drug candidate, which is currently being evaluated in phase II clinical studies for the treatment of Sleep Initiation and Maintenance Disorders.
Product Name : Undisclosed
Product Type : Controlled Substance
Upfront Cash : Inapplicable
October 26, 2022

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Details:
DAYVIGO (Lemborexant), an orexin receptor antagonist, is Eisai’s in-house discovered and developed small molecule that inhibits orexin neurotransmission by binding competitively to the two subtypes of orexin receptors (orexin receptor 1 and 2).
Lead Product(s): Lemborexant,Inapplicable
Therapeutic Area: Sleep Brand Name: Dayvigo
Study Phase: Approved FDFProduct Type: Controlled Substance
Sponsor: Undisclosed
Deal Size: Inapplicable Upfront Cash: Inapplicable
Deal Type: Inapplicable June 02, 2022

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Lead Product(s) : Lemborexant,Inapplicable
Therapeutic Area : Sleep
Highest Development Status : Approved FDF
Partner/Sponsor/Collaborator : Undisclosed
Deal Size : Inapplicable
Deal Type : Inapplicable
Eisai to Present Latest Data on Lemborexant at the 36th Annual Sleep 2022 Meeting
Details : DAYVIGO (Lemborexant), an orexin receptor antagonist, is Eisai’s in-house discovered and developed small molecule that inhibits orexin neurotransmission by binding competitively to the two subtypes of orexin receptors (orexin receptor 1 and 2).
Product Name : Dayvigo
Product Type : Controlled Substance
Upfront Cash : Inapplicable
June 02, 2022

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Details:
DAYVIGO (lemborexant) is a small-molecule compound, discovered and developed by Eisai in-house scientists, that inhibits orexin signaling by binding competitively to both orexin receptor subtypes (orexin receptor 1 and 2).
Lead Product(s): Lemborexant,Inapplicable
Therapeutic Area: Sleep Brand Name: Dayvigo
Study Phase: Approved FDFProduct Type: Controlled Substance
Sponsor: Undisclosed
Deal Size: Inapplicable Upfront Cash: Inapplicable
Deal Type: Inapplicable June 09, 2021

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Lead Product(s) : Lemborexant,Inapplicable
Therapeutic Area : Sleep
Highest Development Status : Approved FDF
Partner/Sponsor/Collaborator : Undisclosed
Deal Size : Inapplicable
Deal Type : Inapplicable
Eisai To Present Latest Data Of Lemborexant At 35th Annual Sleep Meeting (SLEEP2021)
Details : DAYVIGO (lemborexant) is a small-molecule compound, discovered and developed by Eisai in-house scientists, that inhibits orexin signaling by binding competitively to both orexin receptor subtypes (orexin receptor 1 and 2).
Product Name : Dayvigo
Product Type : Controlled Substance
Upfront Cash : Inapplicable
June 09, 2021

FULL SCREEN VIEW Click here to open all results in a new tab [this preview display 10 results](1R,2S)-2-(3-fluorophenyl)-2-(hydroxymethyl)cyclop...
CAS Number : 1369768-29-5
End Use API : Lemborexant
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CAS Number : 412003-95-3
End Use API : Lemborexant
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(1S,2R)-1-(3-Fluorophenyl)-1,2-cyclopropanedimetha...
CAS Number : 1369767-20-3
End Use API : Lemborexant
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1,2-Cyclopropanedimethanol, 1-(3-fluorophenyl)-, ...
CAS Number : 1450904-92-3
End Use API : Lemborexant
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CAS Number : 412003-95-3
End Use API : Lemborexant
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((1R,2S)-2-(3-fluorophenyl)-2-(hydroxymethyl)cyclo...
CAS Number : 1369768-29-5
End Use API : Lemborexant
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CAS Number : 412003-95-3
End Use API : Lemborexant
About The Company : LinkChem is a leading China headquartered CMO | CRO provider within the pharmaceutical industry. Our core focus includes: custom synthesis, process development,...

FULL SCREEN VIEW Click here to open all results in a new tab [this preview display 10 results]Global Sales Information
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Patents & EXCLUSIVITIES
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Exclusivity Code : M-293
Exclusivity Expiration Date : 2026-04-20
Application Number : 212028
Product Number : 1
Exclusivity Details :

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Exclusivity Code : NCE
Exclusivity Expiration Date : 2025-04-07
Application Number : 212028
Product Number : 1
Exclusivity Details :

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Exclusivity Code : M-293
Exclusivity Expiration Date : 2026-04-20
Application Number : 212028
Product Number : 2
Exclusivity Details :

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Exclusivity Code : NCE
Exclusivity Expiration Date : 2025-04-07
Application Number : 212028
Product Number : 2
Exclusivity Details :

FULL SCREEN VIEW Click here to open all results in a new tab [this preview display 10 results]ABOUT THIS PAGE
25
PharmaCompass offers a list of Lemborexant API manufacturers, exporters & distributors, which can be sorted by GMP, USDMF, JDMF, KDMF, CEP (COS), WC, Price,and more, enabling you to easily find the right Lemborexant manufacturer or Lemborexant supplier for your needs.
Send us enquiries for free, and we will assist you in establishing a direct connection with your preferred Lemborexant manufacturer or Lemborexant supplier.
PharmaCompass also assists you with knowing the Lemborexant API Price utilized in the formulation of products. Lemborexant API Price is not always fixed or binding as the Lemborexant Price is obtained through a variety of data sources. The Lemborexant Price can also vary due to multiple factors, including market conditions, regulatory modifications, or negotiated pricing deals.
A Lemborexant manufacturer is defined as any person or entity involved in the manufacture, preparation, processing, compounding or propagation of Lemborexant, including repackagers and relabelers. The FDA regulates Lemborexant manufacturers to ensure that their products comply with relevant laws and regulations and are safe and effective to use. Lemborexant API Manufacturers are required to adhere to Good Manufacturing Practices (GMP) to ensure that their products are consistently manufactured to meet established quality criteria.
click here to find a list of Lemborexant manufacturers with USDMF, JDMF, KDMF, CEP, GMP, COA and API Price related information on PhamaCompass.
A Lemborexant supplier is an individual or a company that provides Lemborexant active pharmaceutical ingredient (API) or Lemborexant finished formulations upon request. The Lemborexant suppliers may include Lemborexant API manufacturers, exporters, distributors and traders.
click here to find a list of Lemborexant suppliers with USDMF, JDMF, KDMF, CEP, GMP, COA and API Price related information on PharmaCompass.
A Lemborexant DMF (Drug Master File) is a document detailing the whole manufacturing process of Lemborexant active pharmaceutical ingredient (API) in detail. Different forms of Lemborexant DMFs exist exist since differing nations have different regulations, such as Lemborexant USDMF, ASMF (EDMF), JDMF, CDMF, etc.
A Lemborexant DMF submitted to regulatory agencies in the US is known as a USDMF. Lemborexant USDMF includes data on Lemborexant's chemical properties, information on the facilities and procedures used, and details about packaging and storage. The Lemborexant USDMF is kept confidential to protect the manufacturer’s intellectual property.
click here to find a list of Lemborexant suppliers with USDMF on PharmaCompass.
Lemborexant Active pharmaceutical ingredient (API) is produced in GMP-certified manufacturing facility.
GMP stands for Good Manufacturing Practices, which is a system used in the pharmaceutical industry to make sure that goods are regularly produced and monitored in accordance with quality standards. The FDA’s current Good Manufacturing Practices requirements are referred to as cGMP or current GMP which indicates that the company follows the most recent GMP specifications. The World Health Organization (WHO) has its own set of GMP guidelines, called the WHO GMP. Different countries can also set their own guidelines for GMP like China (Chinese GMP) or the EU (EU GMP).
PharmaCompass offers a list of Lemborexant GMP manufacturers, exporters & distributors, which can be sorted by USDMF, JDMF, KDMF, CEP (COS), WC, API price, and more, enabling you to easily find the right Lemborexant GMP manufacturer or Lemborexant GMP API supplier for your needs.
A Lemborexant CoA (Certificate of Analysis) is a formal document that attests to Lemborexant's compliance with Lemborexant specifications and serves as a tool for batch-level quality control.
Lemborexant CoA mostly includes findings from lab analyses of a specific batch. For each Lemborexant CoA document that a company creates, the USFDA specifies specific requirements, such as supplier information, material identification, transportation data, evidence of conformity and signature data.
Lemborexant may be tested according to a variety of international standards, such as European Pharmacopoeia (Lemborexant EP), Lemborexant JP (Japanese Pharmacopeia) and the US Pharmacopoeia (Lemborexant USP).