Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Zafirlukast: Difference between pages

{{Short description|Chemical compound}}

{{redirect-distinguish|Accolate|accolade}}

| verifiedrevid = 470635429

| IUPAC_name = Cyclopentyl 3-{2-methoxy-4-[(''o''-tolylsulfonyl)carbamoyl]benzyl}-1-methyl-1''H''-indol-5-ylcarbamate

| width = 275

| tradename = Accolate<ref name="Accolate PI" />

| DailyMedID = Zafirlukast

| pregnancy_AU = B1

| pregnancy_US = B

|pregnancy_US_comment=<ref name="Accolate PI" />

| pregnancy_category =

| legal_AU =

| legal_CA =

| legal_UK = POM

| legal_US =

| legal_status =

| protein_bound = >99% (albumin)<ref name="Accolate PI" />

| metabolites = hydroxylated metabolites<ref name="Accolate PI" />

| excretion = Fecal<ref name="Accolate PI" />

| IUPHAR_ligand = 3322

| ChEBI_Ref = {{ebicite|correct|EBI}}

| C=31 | H=33 | N=3 | O=6 | S=1

| SMILES = Cc1ccccc1S(=O)(=O)NC(=O)c2cc(OC)c(cc2)Cc3cn(C)c4ccc(cc43)NC(=O)OC5CCCC5

| melting_point = 138

| melting_high = 140

'''Zafirlukast''' is an orally administered [[leukotriene receptor antagonist]] (LTRA) used for the chronic treatment of [[asthma]]. While zafirlukast is generally well tolerated, headache and stomach upset often occur. Some rare side effects can occur, which can be life-threatening, such as [[liver failure]]. [[Churg-Strauss]] syndrome has been associated with zafirlukast, but the relationship isn't thought to be causative in nature. Overdoses of zafirlukast tend to be self-limiting.

Zafirlukast, like other LTRAs, works by inhibiting the immune system. Through its action on inflammatory cells in the lungs, zafirlukast reduces the production of inflammatory mediators that are implicated in the pathogenesis of [[asthma]]. Zafirlukast is extensively hepatically metabolized by an enzyme called [[CYP2C9]]. Zafirlukast inhibits the action of [[CYP3A4]], leading to drug–drug interactions with other drugs that are metabolized by CYP3A4. Genetic differences in [[LTC4 synthase]] and [[CYP2C9]] may predict how a person reacts to zafirlukast treatment.

Zafirlukast (brand name Accolate) was the first cysteinyl leukotriene receptor antagonist approved in the United States. It is now approved in many other countries under other brand names.

==Medical uses==

Zafirlukast is [[FDA]]-approved for the prevention and treatment of asthma in adults and children older than 5 years old.<ref name="Accolate PI" /> Like other leukotriene receptor antagonists, zafirlukast is thought to be useful for the long-term treatment of asthma, but it is generally less effective than inhaled glucocorticoids as monotherapy (which are the standard of care) or long-acting beta-2 agonists in combination therapy.<ref name="Mastalerz et al 2010" /> Notably, zafirlukast is ineffective in the event of an acute asthma attack.<ref name="Accolate PI" />

===Available forms===

There are two dosage forms for zafirlukast, notable for their age-adjustments. The 20&nbsp;mg tablet is for adults and children older than age 12, whereas the 10&nbsp;mg tablet is for children between the ages of 5 and 12.<ref name="Accolate PI" /> Tablets should be stored at room temperature, out of direct sunlight, and away from sources of moisture.<ref name="Accolate PI" />

Tablets are for oral administration only.<ref name="Accolate PI" />

===Specific populations===

====Pediatrics====

As a general rule, leukotriene receptor antagonists like zafirlukast are more effective in children that are younger and whose asthma is less [[atopic]].<ref name="Elsevier Ped Asthma">{{cite book |chapter=Asthma in children |title=ClinicalKey |date=October 11, 2017|publisher=Elsevier BV|language=en| chapter-url = https://elsevier.health/en-US/preview/clinical-overview-asthma-in-children }}</ref> Atopy refers to a predisposition towards developing allergic conditions, including [[asthma]], [[hay fever]], and [[eczema]].<ref>{{cite web|title=Asthma, Hay Fever and Eczema: How to Cope with Atopic Triad|url=http://inside.akronchildrens.org/2016/04/29/how-to-cope-with-atopic-triad/|website=Inside Children's Blog|access-date=7 January 2018|date=29 April 2016|archive-date=7 January 2018|archive-url=https://web.archive.org/web/20180107174949/http://inside.akronchildrens.org/2016/04/29/how-to-cope-with-atopic-triad/|url-status=dead}}</ref>

====Geriatrics====

The hepatic [[Clearance (pharmacology)|clearance]] of zafirlukast is impaired in adults 65 years of age and older, resulting in a 2–3 fold increase in the [[Cmax (pharmacology)|maximum plasma concentration]] and the total [[Area under the curve (pharmacokinetics)|area under the curve]]. Zafirlukast may increase the risk for infections (7.0% vs 2.9%, zafirlukast vs. placebo incidence respectively), especially lower respiratory tract infections, in older adults, though the infections noted were not severe.<ref name="Accolate PI" />

====Pregnancy====

Zafirlukast is considered to be "[[pregnancy category]] B." This is due, in part, to the wide safety margin of zafirlukast in animal studies investigating teratogenicity. No teratogenicity has been observed in doses up to 2000&nbsp;mg/kg/day in cynomolgus monkeys, representing an equivalent 20x exposure of the maximum recommended daily oral dose in human adults. However, spontaneous abortions occurred in cynomolgus monkeys at 2000&nbsp;mg/kg/day, though the dose itself was maternally toxic.<ref name="Accolate PI" />

====Lactation====

There is limited research on the use of zafirlukast in women whom are breastfeeding.<ref name="Lactmed">{{cite book | chapter = Zafirlukast | title = Drugs and Lactation Database (LactMed®) [Internet]. | location = Bethesda (MD) | work = National Institute of Child Health and Human Development | date = 2006 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK501489/ |publisher=U.S. National Library of Medicine| pmid = 30000549 |access-date=29 November 2017|language=en}}</ref> Based on data from the manufacturer, it is expected that 0.6% of the maternal weight-adjusted dose would reach a breastfed infant, though the effects in the infant are unknown.<ref name="Lactmed" />

====Renal impairment====

Renal impairment does not appear to affect the pharmacokinetic profile of zafirlukast.<ref name="Accolate PI" />

====Hepatic impairment====

The hepatic clearance of zafirlukast is impaired by significant hepatic impairment. Cirrhosis of the liver can result in an increase in the [[Cmax (pharmacology)|maximum plasma concentration]] and the total [[Area under the curve (pharmacokinetics)|area under the curve]] (a measure of drug exposure) by 50–60%.<ref name="Accolate PI" />

==Contraindications==

Zafirlukast is contraindicated in people that are hypersensitive or allergic to it.<ref name="Accolate PI" />

==Adverse effects==

Zafirlukast is generally well tolerated, though headache and gastrointestinal (GI) upset can occur. The incidence of headache is between 12 and 20%, which is similar to the incidence of headache found in patients taking [[placebos]] in the studies that lead to zafirlukast's approval. GI upset may include nausea, stomach discomfort/pain, and diarrhea. GI complaints can be lessened by taking zafirlukast with food, though this can dramatically impair the amount of drug that gets absorbed into the body (see the section on [[Zafirlukast#Drug-food interactions|drug-food interactions]] below).<ref name="Clinical Asthma Book">{{cite book | vauthors = Sorkness C, Schend V |chapter=Monitoring for Side Effects from Treatment | veditors = Castro M, Kraft M|title=Clinical Asthma |publisher=Mosby |location=Philadelphia, PA |isbn=978-0-323-04289-5 |pages=313–319 |year=2008 }}</ref>

Other common side effects include flu-like symptoms, sleep disturbances (abnormal dreams, insomnia), hallucinations, and daytime drowsiness.<ref name="Clinical Asthma Book" />

===Neuropsychiatric effects===

Neuropsychiatric side effects have been reported with the use of zafirlukast and other LTRAs. While some side effects are less severe (e.g. abnormal dreams), others are more serious (e.g. hallucinations, tremor, suicidality). These effects were discovered through post-marketing reports, as the initial trials were not designed to monitor for neuropsychiatric side effects.<ref name="FDA Psych LTRA Warning">{{cite web | work = Center for Drug Evaluation and Research|title=Drug Safety Information for Healthcare<!-- "Heathcare" in original --> Professionals – Updated Information on Leukotriene Inhibitors: Montelukast (marketed as Singulair), Zafirlukast (marketed as Accolate), and Zileuton (marketed as Zyflo and Zyflo CR) |url= https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm165489.htm |publisher=U.S. Food and Drug Administration |access-date=6 December 2017|archive-url= https://web.archive.org/web/20171114124744/https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm165489.htm |archive-date=November 14, 2017}}</ref>

===Hepatotoxicity===

Zafirlukast can also cause rare but serious side effects like acute liver injury.<ref name="Livertox">{{cite book | chapter = Zafirlukast | chapter-url= https://www.ncbi.nlm.nih.gov/books/NBK547915/| title = LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. | location = Bethesda (MD) | work = National Institute of Diabetes and Digestive and Kidney Diseases | date = 2012 |publisher=U.S. National Library of Medicine| pmid= 31643251|access-date=29 November 2017}}</ref> Zafirlukast-induced hepatotoxicity generally occurs within the first 2–6 months of initiating therapy, though cases have been reported up to 13 months after starting zafirlukast.<ref name="Livertox" /> Zafirlukast-induced hepatotoxicity is characterized by a spectrum of liver damage symptoms, including fatigue, nausea, and right upper quadrant pain followed by dark urine, jaundice and pruritus.<ref name="Livertox" /> Liver enzyme elevations are common, and the pattern usually reflects hepatocellular damage, resembling acute viral hepatitis.<ref name="Livertox" /> It is unclear how the hepatotoxicity occurs, but it may be due to a metabolic intermediate of zafirlukast, since it is metabolized in the liver through the enzyme [[CYP2C9]]. When it does occur it can be fatal, and reexposure with zafirlukast may result in a worse injury.<ref name="Livertox" /> Switching zafirlukast to another medication in the same class (e.g. [[montelukast]]) or in the related class of [[5-lipoxygenase inhibitors]] can be attempted, but caution should be employed.<ref name="Livertox" />

According to the "Dear Health Care Provider" letter from AstraZeneca, zafirlukast-induced hepatotoxicity has occurred predominantly in females.<ref name="Label Change Hepatotox">{{cite web|title=Accolate (zafirlukast) – Labeling Changes|url=https://www.medscape.com/viewarticle/447089#vp_1|website=www.medscape.com|publisher=WebMD LLC|access-date=29 November 2017}}</ref>

===Churg-Strauss syndrome===

Several cases of [[Churg-Strauss]] syndrome, also known as allergic [[angiitis]] and [[granulomatosis]], have been reported with the use of zafirlukast, [[montelukast]], [[pranlukast]], and other asthma medications.<ref name="Wechsler Churg-Strauss Syndr">{{cite journal | vauthors = Wechsler ME, Pauwels R, Drazen JM | title = Leukotriene modifiers and Churg-Strauss syndrome: adverse effect or response to corticosteroid withdrawal? | journal = Drug Safety | volume = 21 | issue = 4 | pages = 241–251 | date = October 1999 | pmid = 10514017 | doi = 10.2165/00002018-199921040-00001 | s2cid = 8124340 }}</ref> When Churg-Strauss syndrome occurs, it tends to occur in people with long-standing asthma and [[sinusitis|sinus inflammation]], chronic oral [[corticosteroid]] use, and the recent initiation of a new anti-asthma therapy (like zafirlukast) in conjunction with tapering the corticosteroids.<ref name="Wechsler Churg-Strauss Syndr" /> While the exact etiology of the development of Churg-Strauss symptoms in proximity to initiating zafirlukast is unknown, it is thought that withdrawal of chronic corticosteroids "unmasks" the previously undetected disease.<ref name="Wechsler Churg-Strauss Syndr" /> Because corticosteroid withdrawal often happens while starting a new anti-asthma medication (like zafirlukast), this explains the rare but notable association.<ref name="Wechsler Churg-Strauss Syndr" /> These cases may represent misdiagnosed asthma, as Churg-Strauss syndrome can induce symptoms of airway obstruction that are akin to an acute asthma exacerbation.<ref name="Wechsler Churg-Strauss Syndr" /> As these asthma-like symptoms are reduced by zafirlukast, the symptoms of Churg-Strauss (e.g. neuropathy) increase due to the lack of the broader, anti-inflammatory coverage that the steroid was providing.<ref name="Wechsler Churg-Strauss Syndr" />

==Overdose==

The highest overdose reported with zafirlukast is 200&nbsp;mg. All overdose patients have survived. Symptoms reported included rash and upset stomach.<ref name="Accolate PI" />

== Interactions ==

===Drug–drug interactions===

Zafirlukast is an inhibitor of the hepatic drug-metabolizing enzyme [[CYP3A4|cytochrome P450 family 3 subfamily A member 4]] (CYP3A4).<ref name="Accolate PI" /> Zafirlukast may increase the concentration of drugs that are metabolized through CYP3A4, such as the anticoagulant medication [[warfarin]] and the antiepileptic drugs [[phenytoin]] and [[carbamazepine]].<ref name="Accolate PI" />

===Drug-food interactions===

The oral absorption (bioavailability) of zafirlukast is decreased by 40% when it is taken with high fat or high protein meals.<ref name="Accolate PI" /> To avoid this interaction, zafirlukast should be taken on an empty stomach.<ref name="Clinical Asthma Book" /> An empty stomach is classified as an hour before, or two hours after, consuming a meal.<ref name="Accolate PI" />

==Pharmacology==

===Pharmacodynamics===

Zafirlukast is an antagonist of [[CysLT1|cysteinyl leukotriene receptor 1 (CysLT1)]], a receptor found throughout the smooth muscle of the [[lungs]], within interstitial lung [[macrophages]] (white blood cells that operate in the interstitial space of the lungs), and rarely in epithelial cells.<ref name="Rovati et al 2007">{{cite journal | vauthors = Rovati GE, Capra V | title = Cysteinyl-leukotriene receptors and cellular signals | journal = TheScientificWorldJournal | volume = 7 | pages = 1375–1392 | date = September 2007 | pmid = 17767356 | pmc = 5901261 | doi = 10.1100/tsw.2007.185 | doi-access = free }}</ref> CystLT1 is a receptor for a specific class of [[leukotrienes]] that contain the amino acid [[cysteine]].<ref name="Mastalerz et al 2010">{{cite journal | vauthors = Mastalerz L, Kumik J | title = Antileukotriene drugs in the treatment of asthma | journal = Polskie Archiwum Medycyny Wewnetrznej | volume = 120 | issue = 3 | pages = 103–108 | date = March 2010 | pmid = 20332717 }}</ref> These cysteinyl leukotrienes include [[leukotriene C4]], [[leukotriene D4]], and [[leukotriene E4]], all of which are produced by inflammatory cells like [[eosinophils]], [[basophils]], and [[macrophages]] in the lungs.<ref name="Mastalerz et al 2010" /> Through their action on CysLT1 these leukotrienes can trigger [[bronchoconstriction]], a state in which the bronchial passages of the lungs constrict,<ref name="Dictionary Bronchoconstriction">{{cite web|title=Medical Definition of Bronchoconstriction|url=https://www.merriam-webster.com/medical/bronchoconstriction|website=www.merriam-webster.com|publisher=Merriam-Webster, Incorporated|access-date=29 November 2017|language=en}}</ref> leading to the characteristic, reactive airway symptoms associated with bronchial [[asthma]].<ref name="Mastalerz et al 2010" /> The other pro-inflammatory effects of leukotrienes, such as their inhibition of mucus clearance and their stimulation of mucus secretion and edema, are thought to play a role in the characteristic symptoms of [[allergic rhinitis]] (also called hay fever<ref name="Dictionary Allergic Rhin">{{cite web|title=Medical Definition of Allergic Rhinitis |url=https://www.merriam-webster.com/dictionary/allergic%20rhinitis|website=www.merriam-webster.com|publisher=Merriam-Webster, Incorporated|access-date=29 November 2017}}</ref>).<ref name="Mastalerz et al 2010" /> By inhibiting the action of these specific leukotrienes, zafirlukast is thought to exert an anti-inflammatory effect against leukotriene-mediated inflammatory conditions.<ref name="Mastalerz et al 2010" />

===Pharmacokinetics===

====Absorption====

Zafirlukast is rapidly absorbed into the bloodstream following oral administration, reaching [[Cmax (pharmacology)|peak plasma levels]] within 3 hours of taking the dose.<ref name="Accolate PI">{{cite web|title=ACCOLATE (zafirlukast) Package Insert|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020547s027lbl.pdf|website=www.accessdata.fda.gov|publisher=AstraZeneca LP|access-date=29 November 2017}}</ref> The peak plasma level is the maximum concentration of zafirlukast in the blood.<ref name="Comp Tox">{{cite book| vauthors = Valentine JL, Shyu WC, Grossman SJ | chapter = The Application of ADME Principles in Pharmaceutical Safety Assessment | veditors = McQueen CA |title=Comprehensive Toxicology|edition=2nd | date = June 2010 | pages = 123–136 | publisher = Elsevier | isbn = 978-0-08-046884-6 |quote=Cmax is the maximum concentration of the drug achieved in the plasma following dose administration and Tmax is the time at which Cmax is attained.}}</ref>

====Distribution====

Zafirlukast is moderately distributed into the body's tissues, with an apparent [[steady state (pharmacokinetics)|steady state]] [[volume of distribution]] of 70 liters.<ref name="Accolate PI" /> Zafirlukast is highly plasma protein bound, 99% bound to [[albumin]].<ref name="Accolate PI" /> Albumin is the most abundant protein found in human plasma and is capable of carrying and transporting drugs (like zafirlukast) throughout the body.<ref>{{cite web|title=Plasma albumin|url=https://medical-dictionary.thefreedictionary.com/plasma+albumin|website=TheFreeDictionary.com|publisher=Saunders|access-date=7 January 2018}}</ref> ''In vivo'' research indicates that zafirlukast has low [[blood–brain barrier]] penetration.<ref name="Accolate PI" /> The blood–brain barrier is a protective system that prevents many chemicals from entering the brain.<ref name="pmid9228664">{{cite journal | vauthors = de Vries HE, Kuiper J, de Boer AG, Van Berkel TJ, Breimer DD | title = The blood-brain barrier in neuroinflammatory diseases | journal = Pharmacological Reviews | volume = 49 | issue = 2 | pages = 143–155 | date = June 1997 | pmid = 9228664 | url = http://pharmrev.aspetjournals.org/content/49/2/143.long }}</ref>

====Metabolism====

Zafirlukast undergoes extensive hepatic metabolism into inactive metabolites.<ref name="Accolate PI" /> Zafirlukast is primarily metabolized by the enzyme [[CYP2C9]] to a [[Hydroxylation|hydroxylated]] metabolite.<ref name="Accolate PI" />

====Elimination====

Zafirlukast is primarily cleared through biliary excretion at a rate of 20 liters/hour. Zafirlukast is undetectable in urine. The mean terminal half-life ranges 8–16 hours, following linear kinetics up to doses of 80&nbsp;mg.<ref name="Accolate PI" />

===Pharmacogenomics===

====LTC4 synthase====

Genetic polymorphisms in the [[LTC4 synthase]] [[Promoter (genetics)|promoter]] may predict response to zafirlukast. The [[single-nucleotide polymorphism]] (SNP) A444C (the wild-type DNA base [[adenine]], at the 444th position on the gene, is mutated; [[cytosine]] is there instead), which is associated with a severe asthma phenotype, has been shown to decrease the clinical response to zafirlukast (both when the genetic alteration was heterozygous or homozygous).<ref name="Capra et al 2007" />

====CYP2C9====

Zafirlukast is metabolized through the hepatic enzyme [[CYP2C9]]. SNPs that decrease the function of CYP2C9 (such as [[CYP2C9*3]] and [[CYP2C9*13]]) may decrease the hepatic [[Clearance (pharmacology)|clearance]] of zafirlukast, leading to increased exposure of zafirlukast.<ref name="PharmGKB Clin Annotation">{{cite web|title=Clinical Annotation for CYP2C9*1CYP2C9*13CYP2C9*3 related to zafirlukast|url=https://www.pharmgkb.org/chemical/PA451949/clinicalAnnotation/1448123060|website=PharmGKB|access-date=29 November 2017}}</ref> Notably, the CYP2C9*3 polymorphism is more commonly encountered in people of south/central Asian ancestry (10.165%) compared to people of Caucasian (7.083%), African American (1.170%), African (1.033%), middle eastern (9.312%), and east Asian (3.365%) ancestry.<ref name="CYP2C9 Allele Table">{{cite web|title=CYP2C9 Allele Functionality Table |url= https://api.pharmgkb.org/v1/download/file/attachment/CYP2C9_allele_definition_table.xlsx |website=PharmGKB |access-date=29 November 2017 }}</ref>

==Chemistry==

===Synthesis===

Zafirlukast can be synthesized by the following method:<ref name="Goverdhan et al 2014">{{cite journal| vauthors = Goverdhan G, Reddy AR, Himabindu V, Reddy GM |title=Synthesis and characterization of critical process related impurities of an asthma drug – Zafirlukast |journal=Journal of Saudi Chemical Society |date=April 2014 |volume=18 |issue=2 |pages=129–138 |doi=10.1016/j.jscs.2011.06.002 |doi-access=free }}</ref>

[[File:Zafirlukast synthesis.jpg|Zafirlukast synthesis, drawn with ChemSketch.]]

===Physiochemical properties===

Pure zafirlukast is described as a fine, white to pale yellow, amorphous powder. It is practically insoluble in water, slightly soluble in [[methanol]], and freely soluble in [[tetrahydrofuran]], [[dimethylsulfoxide]], and [[acetone]].<ref name="Accolate PI" />

==History==

Zafirlukast was the first cysteinyl leukotriene receptor antagonist approved in the United States.<ref name="Wechsler Churg-Strauss Syndr" /> Zafirlukast was approved in 1996.<ref name="Wechsler Churg-Strauss Syndr" />

==Society and culture==

===Economics===

While preliminary evidence suggests that zafirlukast may reduce healthcare costs, the cost-effectiveness of using zafirlukast has not been established.<ref name="Dunn et al">{{cite journal | vauthors = Dunn CJ, Goa KL | title = Zafirlukast: an update of its pharmacology and therapeutic efficacy in asthma | journal = Drugs | volume = 61 | issue = 2 | pages = 285–315 | date = 2001 | pmid = 11270943 | doi = 10.2165/00003495-200161020-00012 | s2cid = 249894596 }}</ref>

===Brand names===

{| class="wikitable mw-collapsible mw-collapsed" style="width:100%"

|+ List of [[trade name]]s for zafirlukast<ref name="Brand names drugs.com">{{cite web|title=Zafirlukast |url= https://www.drugs.com/international/zafirlukast.html | work =Drugs.com |access-date=29 November 2017}}</ref>

|-

|A||Accolate, Accoleit, Aeronix

|-

|B||Benalucost

|-

|C||

|-

|D||

|-

|E||

|-

|F||Freesy

|-

|G||

|-

|H||

|-

|I||

|-

|J||

|-

|K||

|-

|L||

|-

|M||Monokast

|-

|N||

|-

|O||Olmoran

|-

|P||

|-

|Q||

|-

|R||

|-

|S||

|-

|T||

|-

|U||

|-

|V||Ventair

|-

|W||

|-

|X||

|-

|Y||

|-

|Z||Zafnil, Zalukast, Zukast

|-

|}

==Research==

===Mechanism of action===

There is some research to suggest that zafirlukast actually acts as a partial inverse agonist at the CysLT1 receptor, though zafirlukast is still classified as an antagonist at this receptor. The possible clinical significance of this effect, if true, is unknown.<ref name="Capra et al 2007">{{cite journal | vauthors = Capra V, Thompson MD, Sala A, Cole DE, Folco G, Rovati GE | title = Cysteinyl-leukotrienes and their receptors in asthma and other inflammatory diseases: critical update and emerging trends | journal = Medicinal Research Reviews | volume = 27 | issue = 4 | pages = 469–527 | date = July 2007 | pmid = 16894531 | doi = 10.1002/med.20071 | s2cid = 24103280 }}</ref>

===Other indications===

There is some evidence that suggests that zafirlukast may be beneficial in the treatment of chronic urticaria (hives), whether due to a known cause such as cold-exposure or due to an unknown cause (idiopathic).<ref name="Capra et al 2007" /> A pilot study indicated that zafirlukast may be of some benefit in [[cystic fibrosis]].<ref name="Capra et al 2007" /> In the setting of [[chronic obstructive pulmonary disorder]] (COPD), a disease characterized by chronic inflammation of the lungs, zafirlukast has been shown to improve lung function.<ref name="Capra et al 2007" />

==Veterinary use==

Zafirlukast is sometimes used for the treatment of bronchial asthma in cats.<ref name="Vet Bronch Asthma">{{cite journal | vauthors = Byers CG, Dhupa N | title = Feline bronchial asthma: treatment. | journal = Compend Contin Educ Pract Vet. | date = June 2005 | volume = 27 | issue = 6 | pages = 426–32 | url= https://vetfolio-vetstreet.s3.amazonaws.com/mmah/e0/851d9448f34096b5d002b5bae51db2/filePV_27_06_426.pdf }}</ref>

== References ==

{{Reflist}}

== External links ==

* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/zafirlukast | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Zafirlukast }}

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