Lemborexant, sold under the brand name Dayvigo, is an

orexin antagonist An orexin receptor antagonist, or orexin antagonist, is a drug that inhibits the effect of orexin by acting as a receptor antagonist of one or both of the orexin receptors, OX1 and OX2. Medical applications include treatment of sleep disorders ...

medication which is used in the treatment of

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

. It is indicated specifically for the treatment of insomnia characterized by difficulties with

sleep onset Sleep onset is the transition from wakefulness into sleep. Sleep onset usually transmits into non-rapid eye movement sleep (NREM sleep) but under certain circumstances (e.g. narcolepsy) it is possible to transit from wakefulness directly into rapid ...

and/or

maintenance Maintenance may refer to: Biological science * Maintenance of an organism * Maintenance respiration Non-technical maintenance * Alimony, also called ''maintenance'' in British English * Champerty and maintenance, two related legal doct ...

in adults. The medication is taken

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

Side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s of lemborexant include

somnolence Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...

fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

, and abnormal dreams. The medication is a dual orexin receptor antagonist (DORA). It acts as a selective dual

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, ri ...

of the

orexin receptor The orexin receptor (also referred to as the hypocretin receptor) is a G-protein-coupled receptor that binds the neuropeptide orexin. There are two variants, OX1 and OX2, each encoded by a different gene (, ). Both orexin receptors exhibit ...

s OX₁ and OX₂. Lemborexant has a long

elimination half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the b ...

of 17 to 55hours and a time to peak of about 1 to 3hours. It is not a

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...

Z-drug Nonbenzodiazepines (), sometimes referred to colloquially as Z-drugs (as many of their names begin with the letter "z"), are a class of psychoactive drugs that are very benzodiazepine-like in nature. They are used in the treatment of sleep proble ...

and does not interact with

GABA receptor The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid (GABA), the chief inhibitory compound in the mature vertebrate central nervous system. There are two classes of GABA receptors: GABAA and ...

s, instead having a distinct

mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targ ...

. Lemborexant was approved for medical use in the United States in December 2019. It is a schedule IV

controlled substance A controlled substance is generally a drug or chemical whose manufacture, possession and use is regulated by a government, such as illicitly used drugs or prescription medications that are designated by law. Some treaties, notably the Single ...

in the United States and may have a low potential for misuse. Besides lemborexant, other orexin receptor antagonists including

suvorexant Suvorexant, sold under the brand name Belsomra, is an orexin antagonist medication which is used in the treatment of insomnia. It is indicated specifically for the treatment of insomnia characterized by difficulties with sleep onset and/or mainte ...

and daridorexant have also been introduced.

Medical uses

Lemborexant is used in the treatment of

in adults. A major

systematic review A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from published studies on t ...

and

network meta-analysis A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...

of medications for the treatment of insomnia published in 2022 found that lemborexant had an

effect size In statistics, an effect size is a value measuring the strength of the relationship between two variables in a population, or a sample-based estimate of that quantity. It can refer to the value of a statistic calculated from a sample of data, the ...

(

standardized mean difference In statistics, an effect size is a value measuring the strength of the relationship between two variables in a population, or a sample-based estimate of that quantity. It can refer to the value of a statistic calculated from a sample of data, t ...

(SMD)) against

placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures. In general ...

for treatment of insomnia at 4weeks of 0.36 (95% 0.08 to 0.63) and at 3months of 0.41 (95% 0.04 to 0.78). Lemborexant had similar effect sizes at 4weeks as the other evaluated and marketed orexin receptor antagonists

(SMD 0.31, 95% CI 0.01 to 0.62) and daridorexant (SMD 0.23, 95% CI –0.01 to 0.48), whereas

s and

s generally showed larger effect sizes (e.g., SMDs of 0.45 to 0.83) than lemborexant and the other orexin receptor antagonists. However, the review concluded that lemborexant and

eszopiclone Eszopiclone, sold under the brand-name Lunesta among others such as Night Calm in Egypt, is a medication used in the treatment of insomnia. Evidence supports slight to moderate benefit up to six months. It is taken orally. Common side effects i ...

among all of the insomnia medications assessed had the best profiles overall in terms of

efficacy Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as ''effectiveness'', and it has often been used synonymously, although in pharmacology a distinction is now often made between ...

, tolerability, and

acceptability Acceptability is the characteristic of a thing being subject to acceptance for some purpose. A thing is acceptable if it is sufficient to serve the purpose for which it is provided, even if it is far less usable for this purpose than the ideal exa ...

. Compared to

s, there is a low risk of developing

tolerance Tolerance or toleration is the state of tolerating, or putting up with, conditionally. Economics, business, and politics * Toleration Party, a historic political party active in Connecticut * Tolerant Systems, the former name of Veritas Software ...

and dependence.

Memory Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remember ...

and

attention Attention is the behavioral and cognitive process of selectively concentrating on a discrete aspect of information, whether considered subjective or objective, while ignoring other perceivable information. William James (1890) wrote that "Att ...

are not affected the next morning when taking lemborexant.

Available forms

Lemborexant is available in the form of 5 and 10mg

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid ** Oral administration of medicines ** Oral examination (also known as an oral exam or or ...

film-coated

tablet Tablet may refer to: Medicine * Tablet (pharmacy), a mixture of pharmacological substances pressed into a small cake or bar, colloquially called a "pill" Computing * Tablet computer, a mobile computer that is primarily operated by touching the ...

Side effects

s of lemborexant include

(combined preferred terms of somnolence,

lethargy Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overwo ...

, fatigue, and sluggishness) (6.9% at 5 mg and 9.6% at 10 mg vs. 1.3% for

(5.9% at 5 mg and 4.5% at 10 mg vs. 3.4% for placebo), and

nightmare A nightmare, also known as a bad dream, Retrieved 11 July 2016. is an unpleasant dream that can cause a strong emotional response from the mind, typically fear but also despair, anxiety or great sadness. The dream may contain situations of ...

s or abnormal dreams (0.9% at 5 mg and 2.2% at 10 mg vs. 0.9% for placebo). Less common side effects include sleep paralysis (1.3% at 5 mg and 1.6% at 10 mg vs. 0% for placebo) and

hypnagogic hallucination Hypnagogia is the experience of the transitional state from wakefulness to sleep: the ''hypnagogic'' state of consciousness, during the onset of sleep. Its opposite state is described as the transitional state from sleep into wakefulness. Mental ...

s (0.1% at 5 mg and 0.7% at 10 mg vs. 0% for placebo). Lemborexant at doses of 10, 20, and 30mg produces

drug-liking Drug liking is a measure of the pleasurable (hedonic) experience when a person consumes drugs. It is commonly used to study the misuse liability of drugs. Drug liking is often measured using unipolar and bipolar visual analogue scales (VAS), such ...

responses similar to those of

zolpidem Zolpidem, sold under the brand name Ambien, among others, is a medication primarily used for the short-term treatment of sleeping problems. Guidelines recommend that it be used only after cognitive behavioral therapy for insomnia and behavior ...

(30mg) and

(40mg) in recreational sedative drug users. It is a

in the United States and is considered to have a low misuse potential.

Pharmacology

Pharmacodynamics

Lemborexant is a dual

of the

orexin Orexin (), also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. The most common form of narcolepsy, type 1, in which the individual experiences brief losses of muscle tone ("drop attacks" or cataplexy) ...

OX₁ and OX₂

receptor Receptor may refer to: *Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...

s. It associates and dissociates from the orexin receptors more rapidly than certain other orexin receptor antagonists, such as

, and this may cause it to have a shorter duration of action.

Pharmacokinetics

The

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. Ho ...

of lemborexant is good and is at least 87%. The time to peak levels of lemborexant is 1 to 3 hours. A high-fat and high-calorie meal has been found to delay the time to peak levels by 2 hours. Its plasma protein binding ''

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology a ...

'' is 94%. Lemborexant is

metabolized Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

primarily by

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules ( xenobiotics), such as toxins or drugs, so that they can be removed from ...

and to a lesser extent by CYP3A5. The "effective" half-life of lemborexant is 17 to 19 hours while its terminal elimination half-life is 55 hours. The medication is excreted in

feces Feces ( or faeces), known colloquially and in slang as poo and poop, are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the large intestine. Feces contain a rela ...

(57%) and to a lesser extent

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellul ...

(29%).

Peak normalized-concentrations of suvorexant and lemborexant with administration at steady state in humans

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. In addition, lemborexant dissociates from the orexin receptors more rapidly than does suvorexant. These differences may allow for comparatively reduced next-day effects such as daytime somnolence with lemborexant.

History

In June 2016,

Eisai was a Japanese Buddhist priest, credited with founding the Rinzai school, the Japanese line of the Linji school of Zen Buddhism. In 1191, he introduced this Zen approach to Japan, following his trip to China from 1187 to 1191, during which he w ...

initiated Phase III

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...

s in the United States, France, Germany, Italy, Japan, Poland, Spain and the UK. 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.

Society and culture

Names

''Lemborexant'' is the generic name of the drug and its while ''E-2006'' was its developmental code name. Lemborexant is sold under the brand name Dayvigo.

Availability

Lemborexant is marketed in the United States,

Canada Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by to ...

Australia Australia, officially the Commonwealth of Australia, is a sovereign country comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands. With an area of , Australia is the largest country by ...

, and

Japan Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the n ...

. It is not approved by the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Eur ...

(EMA) for use in the

European Union The European Union (EU) is a supranational union, supranational political union, political and economic union of Member state of the European Union, member states that are located primarily in Europe, Europe. The union has a total area of ...

or by the

Medicines and Healthcare products Regulatory Agency The Medicines and Healthcare products Regulatory Agency (MHRA) is an executive agency of the Department of Health and Social Care in the United Kingdom which is responsible for ensuring that medicines and medical devices work and are acceptab ...

(MHRA) in the

United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Europe, off the north-western coast of the continental mainland. It comprises England, Scotland, Wales and ...

Research

Lemborexant is under development for the treatment of

circadian rhythm sleep disorder Circadian rhythm sleep disorders (CRSD), also known as circadian rhythm sleep-wake disorders (CRSWD), are a family of sleep disorders which affect the timing of sleep. CRSDs arise from a persistent pattern of sleep/wake disturbances that can be ...

sleep apnea Sleep apnea, also spelled sleep apnoea, is a sleep disorder in which pauses in breathing or periods of shallow breathing during sleep occur more often than normal. Each pause can last for a few seconds to a few minutes and they happen many tim ...

, and

chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...

. As of February 2022, it is in

phase 2 Michael Lawrence Marrow (August 2, 1955 – December 12, 2019), known as PHASE 2 and Lonny Wood, was an American aerosol paint artist based in New York City. Mostly active in the 1970s, Phase 2 is generally credited with originating the "bubble l ...

s for circadian rhythm sleep disorders and phase 1 trials for sleep apnea and chronic obstructive pulmonary disease.

References

External links

* {{Portal bar , Medicine Carboxamides Cyclopropanes Fluoroarenes Hypnotics Japanese inventions Orexin antagonists Organofluorides Pyrimidines Pyridines