Lemborexant
Chemical compound From Wikipedia, the free encyclopedia
Lemborexant, sold under the brand name Dayvigo, is an orexin antagonist medication which is used in the treatment of insomnia.[3][8] It is indicated specifically for the treatment of insomnia characterized by difficulties with sleep onset and/or maintenance in adults.[3][8] The medication is taken by mouth.[3][8]
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| Trade names | Dayvigo |
| Other names | E-2006 |
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| Routes of administration | By mouth[3] |
| Drug class | Orexin receptor antagonist; Hypnotic; Sedative |
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| Bioavailability | Good (≥87%)[5][6] |
| Protein binding | 94%[3] |
| Metabolism | Liver (major: CYP3A4, minor: CYP3A5)[3] |
| Metabolites | M10[3] |
| Elimination half-life | 17–19 hours or 55 hours[3][7] |
| Excretion | Feces: 57.4%[3] Urine: 29.1%[3] |
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| Formula | C22H20F2N4O2 |
| Molar mass | 410.425 g·mol−1 |
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Side effects of lemborexant include somnolence, fatigue, headache, and abnormal dreams.[3][8] The medication is a dual orexin receptor antagonist (DORA).[3][8] It acts as a selective dual antagonist of the orexin receptors OX1 and OX2.[3][8] Lemborexant has a long elimination half-life of 17 to 55 hours and a time to peak of about 1 to 3 hours.[3][8] It is not a benzodiazepine or Z-drug and does not interact with GABA receptors, instead having a distinct mechanism of action.[3][8]
Lemborexant was approved for medical use in the United States in December 2019.[9][10][11] It is a schedule IV controlled substance in the United States and may have a low potential for misuse.[3][8] Besides lemborexant, other orexin receptor antagonists including suvorexant and daridorexant have also been introduced.[12][13]
Medical uses
Summarize
Perspective
Lemborexant is used in the treatment of insomnia in adults.[3]
A major systematic review and network meta-analysis of medications for the treatment of insomnia published in 2022 found that lemborexant had an effect size (standardized mean difference (SMD)) against placebo for treatment of insomnia at 4 weeks of 0.36 (95% CI 0.08 to 0.63) and at 3 months of 0.41 (95% CI 0.04 to 0.78).[14] Lemborexant had similar effect sizes at 4 weeks as the other evaluated and marketed orexin receptor antagonists suvorexant (SMD 0.31, 95% CI 0.01 to 0.62) and daridorexant (SMD 0.23, 95% CI –0.01 to 0.48), whereas benzodiazepines and Z-drugs generally showed larger effect sizes (e.g., SMDs of 0.45 to 0.83) than lemborexant and the other orexin receptor antagonists.[14] However, the review concluded that lemborexant and eszopiclone among all of the insomnia medications assessed had the best profiles overall in terms of efficacy, tolerability, and acceptability.[14]
Compared to benzodiazepines, there is a low risk of developing tolerance and dependence.[15] Memory and attention are not affected the next morning when taking lemborexant.[16]
Available forms
Lemborexant is available in the form of 5 and 10 mg oral film-coated tablets.[3]
Side effects
Side effects of lemborexant include somnolence or fatigue (combined preferred terms of somnolence, lethargy, fatigue, and sluggishness) (6.9% at 5 mg and 9.6% at 10 mg vs. 1.3% for placebo), headache (5.9% at 5 mg and 4.5% at 10 mg vs. 3.4% for placebo), and nightmares or abnormal dreams (0.9% at 5 mg and 2.2% at 10 mg vs. 0.9% for placebo).[3] Less common side effects include sleep paralysis (1.3% at 5 mg and 1.6% at 10 mg vs. 0% for placebo) and hypnagogic hallucinations (0.1% at 5 mg and 0.7% at 10 mg vs. 0% for placebo).[3]
Lemborexant at doses of 10, 20, and 30 mg produces drug-liking responses similar to those of zolpidem (30 mg) and suvorexant (40 mg) in recreational sedative drug users.[3] It is a controlled substance in the United States and is considered to have a low misuse potential.[3][17]
Pharmacology
Summarize
Perspective
Pharmacodynamics
Lemborexant is a dual antagonist of the orexin OX1 and OX2 receptors.[18][19][20] It associates and dissociates from the orexin receptors more rapidly than certain other orexin receptor antagonists, such as suvorexant, and this may cause it to have a shorter duration of action.[12]
Pharmacokinetics
The bioavailability of lemborexant is good and is at least 87%.[5][6] The time to peak levels of lemborexant is 1 to 3 hours.[3] A high-fat and high-calorie meal has been found to delay the time to peak levels by 2 hours.[3] Its plasma protein binding in vitro is 94%.[3] Lemborexant is metabolized primarily by CYP3A4 and to a lesser extent by CYP3A5.[3] The "effective" half-life of lemborexant is 17 to 19 hours while its terminal elimination half-life is 55 hours.[3][7][8] The medication is excreted in feces (57%) and to a lesser extent urine (29%).[3]
Although lemborexant has a longer terminal elimination half-life than suvorexant, it appears to be more rapidly cleared than suvorexant in the earlier phases of elimination.[21][7] In addition, lemborexant dissociates from the orexin receptors more rapidly than does suvorexant.[21] These differences may allow for comparatively reduced next-day effects such as daytime somnolence with lemborexant.[21][7]
History
In June 2016, Eisai initiated Phase III clinical trials in the United States, France, Germany, Italy, Japan, Poland, Spain and the UK.[22]
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.[11][23]
Society and culture
Names
Lemborexant is the generic name of the drug and its INN while E-2006 was its developmental code name. Lemborexant is sold under the brand name Dayvigo.[3]
Availability
Lemborexant is marketed in the United States, Canada, Australia, and Japan.[24][25][26][27] It is not approved by the European Medicines Agency (EMA) for use in the European Union or by the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom.[28][29]
Research
Lemborexant is under development for the treatment of circadian rhythm sleep disorders, sleep apnea, and chronic obstructive pulmonary disease.[30] As of February 2022, it is in phase 2 clinical trials for circadian rhythm sleep disorders and phase 1 trials for sleep apnea and chronic obstructive pulmonary disease.[30]
References
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