|Trade names||Singulair, others|
|Drug class||Leukotriene receptor antagonist|
|Defined daily dose||10 mg|
|Metabolism||Liver (CYP2C8-major, CYP3A4 and CYP2C9-minor)|
|Elimination half-life||2.7–5.5 hours|
|Chemical and physical data|
|Molar mass||586.19 g·mol−1|
|3D model (JSmol)|
|Melting point||145 to 148 °C (293 to 298 °F)|
Montelukast, sold under the brand name Singulair among others, is a medication used in the maintenance treatment of asthma. It is generally less preferred for this use than inhaled corticosteroids. It is not useful for acute asthma attacks. Other uses include allergic rhinitis and hives of long duration. For allergic rhinitis it is a second line treatment. It is taken by mouth.
Common side effects include abdominal pain, cough, and headache. Severe side effects may include allergic reactions, such as anaphylaxis and eosinophilia. Use in pregnancy appears to be safe. Montelukast is in the leukotriene receptor antagonist family of medications. It works by blocking the action of leukotriene D4 in the lungs resulting in decreased inflammation and relaxation of smooth muscle.
Montelukast was approved for medical use in the United States in 1998. It is available as a generic medication. In the United States, the wholesale cost per dose is less than 0.15 USD as of 2018. In 2017, it was the 16th most commonly prescribed medication in the United States, with more than 31 million prescriptions.
Montelukast is used for a number of conditions including asthma, exercise induced bronchospasm, allergic rhinitis, and urticaria. It is mainly used as a complementary therapy in adults in addition to inhaled corticosteroids, if inhaled steroids alone do not bring the desired effect. It is also used to prevent allergic reactions and asthma flare-ups during the administration of intravenous immunoglobulin. It may also be used as an adjunct therapy in symptomatic treatment of mastocytosis.
Montelukast is usually taken once a day with or without food.
Common side effects include diarrhea, nausea, vomiting, mild rashes, asymptomatic elevations in liver enzymes, and fever. Uncommon side effects include fatigue and malaise, behavioral changes, paresthesias and seizures, muscle cramps, and nose bleeds. Rare (may affect up to 1 in 10,000 people taking montelukast) but serious side effects include behavioral changes (including suicidal thoughts), angioedema, erythema multiforme, and liver problems.
In 2019 and 2020, concerns for neuropsychiatric reactions were added to the label in the United Kingdom and United States where the most frequently suspected were nightmares, depression, insomnia (may affect between 1 in 100 to 1 in 1,000 people taking montelukast); aggression, anxiety and abnormal behaviour or changes in behaviour (may affect between 1 in 1,000 to 1 in 10,000 people taking montelukast).
In June 2009, the U.S. Food and Drug Administration (FDA) concluded a review into the possibility of neuropsychiatric side effects with leukotriene modulator drugs. Although clinical trials only revealed an increased risk of insomnia, post-marketing surveillance showed that the drugs are associated with a possible increase in suicidal behavior and other side effects such as agitation, aggression, anxiousness, dream abnormalities and hallucinations, depression, irritability, restlessness, and tremor.
In September 2019, the Pediatric Advisory Committee and the Drug Safety and Risk Management Advisory Committee met to discuss a pediatric-focused safety review of neuropsychiatric events with montelukast.
In March 2020, the FDA required a boxed warning for montelukast to strengthen an existing warning about the risk of neuropsychiatric events associated with the drug in the wake of an increase in case reporting of neuropsychiatric events around the time of the initial communications about the concern from FDA in 2008. The boxed warning advises health care providers to avoid prescribing montelukast for people with mild symptoms, particularly those with allergic rhinitis because there are many other effective, less-concerned allergy medicines that are also indicated for the mild cases.
In the FDA's self-conducted data analysis in comparison to their received case reports which were dependent on people's self-claims, the propensity of developing neuropsychiatric disorders after montelukast use does not outpace that of inhaled corticosteroids; and there were no statistically significant risks of new-onset neuropsychiatric disorders among males, females, patients 12 years and older, patients with a psychiatric history, or after the 2008 FDA communication and prescribing information changes that first publicized the concern. In addition, FDA's self-conducted data analysis also summarized their own findings, saying "exposure to montelukast was significantly associated with a decreased risk of treated outpatient depressive disorder and the decreased risks were seen among patients with a history of a psychiatric disorder, in patients 12 to 17 years as well as 18 years and older, and in both females and males." "Treated outpatient depressive disorder" refers to patients' actions of making an appointment with psychiatrists to contend with their depressions.
Montelukast has very few drug-drug interactions. This is due to the lack of off-target affinity towards other targets in the body where it might exert an effect.[medical citation needed] However, it is important to note that montelukast is an inhibitor of the drug metabolizing enzyme CYP2C8. Therefore, it is theoretically possible that the combination of montelukast with a CYP2C8 substrate (e.g. amodiaquine, an anti-malarial drug) could increase the plasma concentrations of the substrate.
Montelukast is in the leukotriene receptor antagonist family of medications. It works by blocking the action of leukotriene D4 in the lungs resulting in decreased inflammation and relaxation of smooth muscle.
Montelukast functions as a leukotriene receptor antagonist (cysteinyl leukotriene receptors) and consequently opposes the function of these inflammatory mediators; leukotrienes are produced by the immune system and serve to promote bronchoconstriction, inflammation, microvascular permeability, and mucus secretion in asthma and COPD. Leukotriene receptor antagonists are sometimes colloquially referred to as leukasts.
Society and culture
In the United States, the wholesale cost per dose is less than 0.15 USD as of 2018. In 2017, it was the 16th most commonly prescribed medication in the United States, with more than 31 million prescriptions.
The United States Patent and Trademark Office launched a reexamination of the patent covering Singulair on May 28, 2009. The decision was driven by the discovery of references that were not included in the original patent application process. The references were submitted through Article One Partners, an online research community focused on finding literature relating to existing patents. The references included a scientific article produced by a Merck employee on the active ingredient in Singulair. A previously filed patent had been submitted in the same technology area. Seven months later the U.S. Patent and Trademark Office determined that the patent in question was valid based on the initial reexamination and new information provided, submitting their decision on December 17, 2009.
Use with loratadine
Schering-Plough and Merck sought permission to market a combined tablet with loratadine and montelukast. However, the FDA has found no benefit from a combined pill for seasonal allergies over taking the two drugs in combination, and on April 25, 2008, issued a not-approvable letter for the combination.
Montelukast is sold under a variety of brand names including Montenaaf (NAAFCO Pharma) Montelon-10 (Apex), Montene (Square), Montair-10, Montelo-10, Monteflo, and Tukast L in India, Reversair (ACI Bangladesh), Miralust, Montiva, Provair, Montril, Lumona, Lumenta, Arokast and Trilock in Bangladesh, Ventair in Nepal, Montika in Pakistan, Montelair in Brazil, Zykast in the Philippines though combined with levocetirizine, Notta in Turkey, Topraz in South Africa and AirOn in Venezuela.
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- "WHOCC - ATC/DDD Index". www.whocc.no. Retrieved 9 September 2020. CS1 maint: discouraged parameter (link)
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- Grainger, J.; Drake-Lee, A. (2006). "Montelukast in allergic rhinitis: a systematic review and meta-analysis". Clinical Otolaryngology. Wiley. 31 (5): 360–367. doi:10.1111/j.1749-4486.2006.01276.x. ISSN 0307-7772. PMID 17014443.
regarded as second line therapy. When used, montelukast should be used in combination with an antihistamine.
- British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 269. ISBN 9780857113382.
- "NADAC as of 2018-12-19". Centers for Medicare and Medicaid Services. Retrieved 22 December 2018.
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- Montelukast article on Medline Plus https://www.nlm.nih.gov/medlineplus/druginfo/meds/a600014.html "Montelukast comes as a tablet, a chewable tablet, and granules to take by mouth. Montelukast is usually taken once a day with or without food."
- "Montelukast (Singulair): reminder of the risk of neuropsychiatric reactions". Retrieved 19 September 2019.
- "Singulair (montelukast) and All Generics: Strengthened Boxed Warning". U.S. Food and Drug Administration (FDA). 4 March 2020. Retrieved 4 March 2020. This article incorporates text from this source, which is in the public domain.
- "Updated Information on Leukotriene Inhibitors: Montelukast (marketed as Singulair), Zafirlukast (marketed as Accolate), and Zileuton (marketed as Zyflo and Zyflo CR)". U.S. Food and Drug Administration (FDA). 12 June 2009. Archived from the original on 14 November 2017. Retrieved 1 March 2017.
- FDA Joint Pediatric Advisory Committee and Drug Safety and Risk Management Advisory Committee; Notice of Meeting
- "FDA Requires Stronger Warning About Risk of Neuropsychiatric Events Associated with Asthma and Allergy Medication Singulair and Generic Montelukast". U.S. Food and Drug Administration (FDA) (Press release). 4 March 2020. Retrieved 4 March 2020. This article incorporates text from this source, which is in the public domain.
- "FDA requires Boxed Warning about serious mental health side effects for asthma and allergy drug montelukast (Singulair); advises restricting use for allergic rhinitis". U.S.Food and Drug Administration (FDA). 4 March 2020. Retrieved 4 March 2020. This article incorporates text from this source, which is in the public domain.
- Artesunate Amodiaquine Winthrop (artesunate, amodiaquine) [summary of product characteristics]. Gentilly, France: Sanofi-aventis; August 2010. http://www.wipo.int/export/sites/www/research/en/data/sanofi/marketed_products/Artesunate_and_Amodiquine.pdf
- German P, Greenhouse B, Coates C, et al. (March 2007). "Hepatotoxicity due to a drug interaction between amodiaquine plus artesunate and efavirenz". Clin. Infect. Dis. 44 (6): 889–91. doi:10.1086/511882. PMID 17304470.
- Scott JP, Peters-Golden M (September 2013). "Antileukotriene agents for the treatment of lung disease". Am. J. Respir. Crit. Care Med. 188 (5): 538–544. doi:10.1164/rccm.201301-0023PP. PMID 23822826.
- Singular patent details
- "FDA approves first generic versions of Singulair to treat asthma, allergies". 3 August 2012. Retrieved 15 August 2012.
- "U.S. Reexamines Merck's Singulair Patent". Thompson Reuters. 28 May 2009.
- "Merck Says U.S. Agency Upholds Singulair Patent". Thompson Reuters. 17 December 2009.
- Rubenstein, Sarah (28 April 2008). "FDA Sneezes at Claritin-Singulair Combo Pill". The Wall Street Journal.
- "Schering-Plough/MERCK Pharmaceuticals Receives Not-Approvable Letter from FDA for Loratadine/Montelukast". Schering-Plough (Press release). 25 April 2008. Archived from the original on 24 September 2008. Retrieved 17 March 2020.
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