Ketotifen: Difference between revisions

{{Short description|Antihistamine medication}}

{{Distinguish|text=[[Ketoprofen]], a nonsteroidal anti-inflammatory drug with analgesic and antipyretic effects}}

{{Use American English|date=February 2024}}

{{Use dmy dates|date=April 2024}}

{{cs1 config|name-list-style=vanc|display-authors=6}}

{{Infobox drug

| Watchedfields = changed

| verifiedrevid = 457461975

| image = Ketotifen.svg

| width = 175

| alt =

| USAN = ketotifen fumarate

<!-- Clinical data -->

| pronounce =

| tradename = Zaditor,<ref name="Zaditor FDA label" /> Alaway, others

| Drugs.com = {{drugs.com|monograph|ketotifen-fumarate}}

| DailyMedID = Ketotifen

| pregnancy_AU = B1

| pregnancy_AU_comment =

| pregnancy_category =

| routes_of_administration = [[Oral administration|By mouth]], [[Ophthalmic drug administration|eye drops]], drug-eluting contact lenses

| class =

| ATC_prefix = R06

| ATC_suffix = AX17

| ATC_supplemental = {{ATC|S01|GX08}}

<!-- Legal status -->

| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->

| legal_AU_comment =

| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->

| legal_BR_comment =

| legal_CA = Rx-only

| legal_CA_comment = <ref name="Zaditen CA PI">{{cite web | title=Zaditen Product information | website=[[Health Canada]] | date=22 October 2009 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=10832 | access-date=10 March 2024 | archive-date=10 March 2024 | archive-url=https://web.archive.org/web/20240310192609/https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=10832 | url-status=live }}</ref><ref name="zaditor-ca">{{cite web | title=Zaditor Product information | website=[[Health Canada]] | date=22 October 2009 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=66035 | access-date=10 March 2024 | archive-date=10 March 2024 | archive-url=https://web.archive.org/web/20240310192610/https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=66035 | url-status=live }}</ref>

| legal_DE = <!-- Anlage I, II, III or Unscheduled -->

| legal_DE_comment =

| legal_NZ = <!-- Class A, B, C -->

| legal_NZ_comment =

| legal_UK = POM

| legal_UK_comment = <ref name="Zaditen-EMC">{{cite web | title=Zaditen Summary of Product Characteristics (SmPC) | website=emc | date=13 October 2020 | url=https://www.medicines.org.uk/emc/product/4327/smpc | access-date=10 March 2024 | archive-date=10 March 2024 | archive-url=https://web.archive.org/web/20240310192610/https://www.medicines.org.uk/emc/product/4327/smpc | url-status=live }}</ref>

| legal_US_comment = /{{nbsp}}Rx-only<ref name="Zaditor FDA label" /><ref name="dailymed-lens" />

| legal_EU =

| legal_EU_comment =

| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->

| legal_UN_comment =

| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->

| metabolism = [[Liver]]

| metabolites =

| onset =

| elimination_half-life = 12 hours

| duration_of_action =

| excretion =

<!-- Identifiers -->

| index2_label = as fumarate

| CAS_number = 34580-13-7

| CAS_number2 = 34580-14-8

| CAS_supplemental =

| PubChem2 = 5282408

| IUPHAR_ligand = 7206

| DrugBank2 = DBSALT001856

| ChemSpiderID2 = 4445563

| UNII = X49220T18G

| UNII2 = HBD503WORO

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D08105

| KEGG2 = D01332

| ChEBI = 92511

| ChEBI2 = 31750

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL2 = 1633

| NIAID_ChemDB =

| PDB_ligand =

| synonyms =

<!-- Chemical and physical data -->

| IUPAC_name = 4-(1-Methylpiperidin-4-ylidene)-4,9-dihydro-10''H''-benzo[4,5]cyclohepta[1,2-''b'']thiophen-10-one

| C=19 | H=19 | N=1 | O=1 | S=1

| SMILES = O=C3c1sccc1C(\c2c(cccc2)C3)=C4/CCN(C)CC4

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI_comment =

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey2 = YNQQEYBLVYAWNX-WLHGVMLRSA-N

| density =

| density_notes =

| melting_point =

| melting_high =

| melting_notes =

| boiling_point =

| boiling_notes =

| solubility =

| sol_units =

| specific_rotation =

'''Ketotifen''' is an [[antihistamine]] medication and a [[mast cell stabilizer]] used to treat allergic conditions such as [[conjunctivitis]], [[asthma]], and urticaria (hives). Ketotifen is available in ophthalmic (eye drops or drug-eluting contact lenses) and oral (tablets or syrup) forms: the ophthalmic form relieves eye [[itchiness]] and irritation associated with [[seasonal allergies]], while the oral form helps prevent [[systemic condition]]s such as asthma attacks and allergic reactions. In addition to treating allergies, ketotifen has shown efficacy in managing systemic [[mast cell disease]]s such as [[mastocytosis]] and [[mast cell activation syndrome]] (MCAS), which involve abnormal accumulation or activation of [[mast cell]]s throughout the body. Ketotifen is also used for other allergic-type conditions like [[atopic dermatitis]] ([[eczema]]) and [[food allergies]].

Ketotifen acts by blocking the [[Histamine H1 receptor|H₁ histamine receptors]], which are found on various cells in the body, such as [[smooth muscle]], [[endothelium]], and [[nerve cells]], so that ketotifen prevents the binding of histamine to these receptors and thus reduces the symptoms of histamine-mediated reactions, such as itching, sneezing, wheezing, and swelling. Ketotifen also prevents the release of histamine and other inflammatory substances from immune cells called mast cells; this action helps reduce symptoms of conditions (including allergic conditions) by blocking the activation of these cells. In addition to its [[Antihistamine|antihistaminic]] activity, ketotifen also functions as a [[leukotriene antagonist]], which blocks inflammation-causing chemicals known as [[leukotriene]]s; it also acts as a [[phosphodiesterase inhibitor]] that regulates blood vessel dilation.

While well-tolerated, ketotifen can have side effects, including drowsiness, weight gain, dry mouth, irritability, increased nosebleeds when taken orally, and temporary burning or stinging sensations in the eyes when used in ophtalmic form. Ketotifen has contraindications for individuals with certain medical conditions, such as acute [[porphyria]]s or [[epilepsy]]. Controversies surrounding ketotifen include its classification as a first-generation or second-generation antihistamine due to varying criteria of classification.

Research on ketotifen continues to explore its impact on appetite regulation and effectiveness against specific medical conditions like [[irritable bowel syndrome]]. Despite inconclusive evidence regarding its efficacy in asthma treatment compared to other medications like [[montelukast]], long-term administration of oral ketotifen has shown positive outcomes in reducing [[Glucocorticoid|corticosteroid use]] while improving clinical symptoms related to [[asthma]] management.

==Medical uses==

Ketotifen, an antihistamine medication and a mast cell stabilizer, is most commonly sold as a [[salt (chemistry)|salt]] with [[fumaric acid]], ketotifen fumarate, and is available in two forms:<ref name="pmid2226222"/>

# in its [[Ophthalmology|ophthalmic]] form (eye drops or drug-eluting contact lenses),<ref name="pmid36000122">{{cite journal |vauthors=Ono J, Toshida H |title=Use of Ketotifen Fumarate-Eluting Daily Disposable Soft Contact Lens in Management of Ocular Allergy: Literature Review and Report of Two Cases |journal=Cureus |volume=14 |issue=7 |pages=e27093 |date=July 2022 |pmid=36000122 |pmc=9391663 |doi=10.7759/cureus.27093 |doi-access=free | title-link=doi }}</ref><ref name="dailymed-lens">{{cite web|url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d222d68c-911e-48a9-9bde-a1ca7e992d18|title=Acuvue Theravision with ketotifen |website=DailyMed |date=11 March 2022|archive-url=https://web.archive.org/web/20231203205156/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d222d68c-911e-48a9-9bde-a1ca7e992d18|archive-date=3 December 2023|url-status=live}}</ref><ref name="pmid23902458">{{cite journal |vauthors=García-Martín E, Canto G, Agúndez JA |title=Metabolic considerations of drugs in the treatment of allergic diseases |journal=Expert Opin Drug Metab Toxicol |volume=9 |issue=11 |pages=1437–52 |date=November 2013 |pmid=23902458 |doi=10.1517/17425255.2013.823400 |s2cid=30634949}}</ref> it is used to treat [[allergic conjunctivitis]];<ref name="pmid36816214">{{cite journal |vauthors=Dou XY, Zhang W |title=Topical ketotifen treatment for allergic conjunctivitis: a systematic review and Meta-analysis |journal=Int J Ophthalmol |volume=16 |issue=2 |pages=286–292 |date=2023 |pmid=36816214 |pmc=9922628 |doi=10.18240/ijo.2023.02.17 |doi-access=free | title-link=doi }}</ref><ref name="Zaditor FDA label">{{cite web | title=Zaditor- ketotifen fumarate solution | website=DailyMed | date=13 February 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ac66b1e4-c2b0-a4c3-09e3-ebd44a2f7c9f | access-date=4 September 2020 | archive-date=11 June 2021 | archive-url=https://web.archive.org/web/20210611120517/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ac66b1e4-c2b0-a4c3-09e3-ebd44a2f7c9f | url-status=live }}</ref>

# in its [[Oral administration|oral]] form (tablets or syrup),<ref name="pmid2226222"/> it is used to prevent [[asthma]] attacks or anaphylaxis,<ref name="Zuberbier et al 2009">{{cite journal | vauthors = Zuberbier T, Asero R, Bindslev-Jensen C, Walter Canonica G, Church MK, Giménez-Arnau AM, Grattan CE, Kapp A, Maurer M, Merk HF, Rogala B, Saini S, Sánchez-Borges M, Schmid-Grendelmeier P, Schünemann H, Staubach P, Vena GA, Wedi B | title = EAACI/GA(2)LEN/EDF/WAO guideline: management of urticaria | journal = Allergy | volume = 64 | issue = 10 | pages = 1427–1443 | date = October 2009 | pmid = 19772513 | doi = 10.1111/j.1398-9995.2009.02178.x | s2cid = 14587946 }}</ref><ref name="Celestin-2015">{{cite conference | vauthors = Li Z, Celestin J |date=23 February 2015 |title=Ketotifen: A Role in the Treatment of Idiopathic Anaphylaxis |conference=American Academy of Allergy, Asthma & Immunology Annual Meeting |location=Houston }}</ref> as well as various mast cell, allergic-type disorders.<ref name="pmid24267353" /><ref name="Shawky-2015">{{cite journal |doi=10.1016/j.ejmhg.2015.04.003 |title=The relation between antihistamine medication during early pregnancy & birth defects |journal=Egyptian Journal of Medical Human Genetics |volume=16 |issue=4 |pages=287–90 |year=2015 | vauthors = Shawky RM, Seifeldin NS |doi-access=free | title-link=doi }}</ref><ref name="pmid23282889">{{cite journal | vauthors = Zuberbier T | title = A Summary of the New International EAACI/GA(2)LEN/EDF/WAO Guidelines in Urticaria | journal = The World Allergy Organization Journal | volume = 5 | issue = Suppl 1 | pages = S1–S5 | date = January 2012 | pmid = 23282889 | pmc = 3488932 | doi = 10.1186/1939-4551-5-S1-S1 | doi-access = free | title-link = doi }}</ref>

Ketotifen ophthalmic solution (eye drops) relieves and prevents eye itchiness and/or irritation associated with most [[allergen|seasonal allergies]]. It starts working within minutes after administering the drops. Ketotifen in the form of eye drops has not been studied in children under three years old,<ref name="Zaditor FDA label" /> whereas drug-eluting contact lenses have not been studied in children under eleven years old.<ref name="dailymed-lens"/>

Drug-eluting contact lenses, which release ketotifen medication, are used to help prevent itchy eyes caused by allergies. The lenses can also correct vision problems like nearsightedness and farsightedness. These lenses are meant for people who don't have red eyes, can comfortably wear contact lenses, and have less than 1 degree of astigmatism.<ref name="dailymed-lens"/>

Oral ketotifen is used to treat asthma, [[allergic rhinitis]], [[allergic conjunctivitis]], [[atopic dermatitis]], [[chronic urticaria]] (hives), cold-induced urticaria, [[cholinergic urticaria]], [[exercise-induced urticaria]], systemic mast cell diseases such as [[mastocytosis]] and [[mast cell activation syndrome]] (MCAS), as well as allergic and nonallergic [[anaphylaxis]]. Ketotifen has also shown efficacy in managing [[angioedema]] and food allergies. As a mast cell stabilizer to treat MCAS, oral ketotifen prevents the release of histamine and other inflammatory substances from [[mast cell]]s, which are [[immune cells]] that react to allergens, therefore, ketotifen, by blocking a [[calcium channel]] essential for mast cell activation, helps reduce symptoms of allergic conditions such as asthma, hay fever, and conjunctivitis caused by mast cell activation. In Canada, Europe, and Mexico, oral ketotifen is commonly prescribed for these indications.<ref name="pmid34238222">{{cite journal | vauthors = El-Alali EA, Abukhiran IM, Alhmoud TZ | title = Successful use of montelukast in eosinophilic gastroenteritis: a case report and a literature review | journal = BMC Gastroenterology | volume = 21 | issue = 1 | pages = 279 | date = July 2021 | pmid = 34238222 | pmc = 8265096 | doi = 10.1186/s12876-021-01854-x | doi-access = free | title-link = doi }}</ref><ref name="pmid23282889"/><ref name="Zuberbier et al 2009"/> In patients with MCAS, ketotifen reduce episodes of [[Flushing (physiology)|flushing]], gastrointestinal symptoms (such as abdominal pain, diarrhea), respiratory symptoms (such as wheezing), and other systemic manifestations. Still, treatment plans for MCAS typically involve a combination of medications targeting different aspects of mast cell activation along with lifestyle modifications to minimize triggers.<ref name="pmid25944644">{{cite journal |vauthors=Frieri M |title=Mast Cell Activation Syndrome |journal=Clin Rev Allergy Immunol |volume=54 |issue=3 |pages=353–365 |date=June 2018 |pmid=25944644 |doi=10.1007/s12016-015-8487-6 |s2cid=5723622 }}</ref>

Oral ketotifen is available at compounding pharmacies in the United States with a prescription requirement, still, the use of oral ketotifen is only approved by the [[Food and Drug Administration]] (FDA) for adults and older children with asthma or allergic conditions.<ref name="pmid23282889"/><ref name="Zuberbier et al 2009"/> However, ketotifen eye drops are approved in the US for people who are at least three years of age.<ref name="Acuvue Theravision with ketotifen-2022">{{cite web|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/022388s000lbl.pdf|year=2022|title=Acuvue Theravision with ketotifen (etafilcon A drug-eluting contact lens with ketotifen), for ophthalmic use|access-date=13 April 2024|archive-date=8 March 2024|archive-url=https://web.archive.org/web/20240308064948/https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/022388s000lbl.pdf|url-status=live}}</ref><ref name="monograph-ophtalmologic"/> In the EU, ketotifen oral formulatios (syrup, tables and capsules) are approved by the [[European Medicines Agency]] for adult use.<ref name="European Medicines Agency-2018">{{Cite web |url=https://www.ema.europa.eu/en/documents/psusa/ketotifen-oral-formulations-list-nationally-authorised-medicinal-products-psusa00001813201710_en.pdf |title=List of nationally authorised medicinal products|publisher=[[European Medicines Agency]]|date=14 June 2018 |access-date=13 April 2024 |archive-date=13 April 2024 |archive-url=https://web.archive.org/web/20240413010133/https://www.ema.europa.eu/en/documents/psusa/ketotifen-oral-formulations-list-nationally-authorised-medicinal-products-psusa00001813201710_en.pdf |url-status=live }}</ref> In the UK, ketotifen is available as tables and elixir (liquid).<ref name="Ketotifen Update-2019">{{cite web | url=https://ukmasto.org/ketotifen-update-4th-december-2019/#gsc.tab=0 | title=Ketotifen Update (4th December 2019) | date=4 December 2019 | access-date=13 April 2024 | archive-date=29 November 2023 | archive-url=https://web.archive.org/web/20231129085408/https://ukmasto.org/ketotifen-update-4th-december-2019/#gsc.tab=0 | url-status=live }}</ref>

Oral ketotifen can be used as a long-term control medication for asthma and wheeze in children, and it has been shown to improve the control of asthma by reducing the need for [[bronchodilator]]s, decreasing symptoms, preventing exacerbations, and reducing the use of rescue oral steroids, ketotifen has also been found to be effective when used alone or in combination with other medications. Oral ketotifen is an alternative to inhaled therapy for asthma in children, especially for younger children who may have difficulty using inhalers.<ref name="pmid14973969">{{cite journal |vauthors=Schwarzer G, Bassler D, Mitra A, Ducharme FM, Forster J |title=Ketotifen alone or as additional medication for long-term control of asthma and wheeze in children |journal=Cochrane Database Syst Rev |volume=2004 |issue=1 |pages=CD001384 |date=2004 |pmid=14973969 |pmc=8406918 |doi=10.1002/14651858.CD001384.pub2 }}</ref>

The mean elimination half-life of ketotifen is 12 hours.<ref name="pmid1600111">{{cite journal | vauthors = Grahnén A, Lönnebo A, Beck O, Eckernäs SA, Dahlström B, Lindström B | title = Pharmacokinetics of ketotifen after oral administration to healthy male subjects | journal = Biopharmaceutics & Drug Disposition | volume = 13 | issue = 4 | pages = 255–262 | date = May 1992 | pmid = 1600111 | doi = 10.1002/bdd.2510130404 | s2cid = 72293850 }}</ref> Besides its anti-histaminic activity, it is also a functional [[leukotriene]] antagonist<ref name="pmid31118754">{{cite journal |vauthors=Zhu TH, Zou G, Ding SJ, Li TT, Zhu LB, Wang JZ, Yao YX, Zhang XM |title=Mast cell stabilizer ketotifen reduces hyperalgesia in a rodent model of surgically induced endometriosis |journal=J Pain Res |volume=12 |pages=1359–1369 |date=2019 |pmid=31118754 |pmc=6500880 |doi=10.2147/JPR.S195909 |doi-access=free | title-link=doi |quote=Ketotifen has a stronger effect on stabilizing MCs than sodium cromoglycate. This drug has antihistamine activity and is also a functional leukotriene antagonist}}<!-- Although this article is a primary research, the claim that ketotifen is a functional leukotriene antagonist is a secondary source --></ref> (a medication that blocks the action of leukotrienes, which are chemicals that cause inflammation and narrowing of the airways in some allergic and respiratory conditions)<ref name="Back-2016">{{cite book|chapter=Leukotrienes|doi=10.1007/978-3-7643-8550-7_105 |title=Compendium of Inflammatory Diseases |date=2016 |pages=849–857 |isbn=978-3-7643-8530-9 | vauthors = Bäck M }}</ref><ref name="pmid31135881">{{cite journal |vauthors=Sasaki F, Yokomizo T |title=The leukotriene receptors as therapeutic targets of inflammatory diseases |journal=Int Immunol |volume=31 |issue=9 |pages=607–615 |date=August 2019 |pmid=31135881 |doi=10.1093/intimm/dxz044}}</ref> and a [[phosphodiesterase inhibitor]]<ref name="pmid33918481">{{cite journal |vauthors=Mostafa GA, Bakheit A, AlMasoud N, AlRabiah H |title=Charge Transfer Complexes of Ketotifen with 2,3-Dichloro-5,6-dicyano-p-benzoquinone and 7,7,8,8-Tetracyanoquodimethane: Spectroscopic Characterization Studies |journal=Molecules |volume=26 |issue=7 |date=April 2021 |page=2039 |pmid=33918481 |pmc=8038309 |doi=10.3390/molecules26072039 |doi-access=free | title-link=doi }}</ref><ref name="pmid1702263">{{cite journal | vauthors = Castillo JG, Gamboa PM, García BE, Oehling A | title = Effect of ketotifen on phosphodiesterase activity from asthmatic individuals | journal = Allergologia et Immunopathologia | volume = 18 | issue = 4 | pages = 197–201 | date = 1990 | pmid = 1702263 }}</ref> (a medication that blocks the enzymes that regulate the levels of [[Cyclic adenosine monophosphate|cAMP]] and [[Cyclic guanosine monophosphate|cGMP]], which are molecules that control [[Vasodilation|blood vessel dilation]] and [[Smooth muscle|smooth muscle relaxation]] in the body).<ref name="pmid17307970">{{cite journal |vauthors=Omori K, Kotera J |title=Overview of PDEs and their regulation |journal=Circ Res |volume=100 |issue=3 |pages=309–27 |date=February 2007 |pmid=17307970 |doi=10.1161/01.RES.0000256354.95791.f1 |doi-access=free | title-link=doi }}</ref><ref name="Acuvue Theravision with ketotifen-2022-2">{{cite journal|doi=10.1093/bjaceaccp/mkm039 |title=Phosphodiesterase inhibitors and the cardiovascular system |date=1 December 2007|journal=Continuing Education in Anaesthesia Critical Care & Pain |volume=7 |issue=6 |pages=203–207 | vauthors = Feneck R |doi-access=free | title-link=doi }}</ref>

==Contraindications==

The eye drops are contraindicated for individuals who have a known hypersensitivity to ketotifen or any other ingredient in the formulation, whereas drug-eluting contact lenses are contraindicated for those who experience irritation from wearing contact lenses. Eye drops are not recommended for use in children under three years of age,<ref name="monograph-general">{{cite web | url=https://www.drugs.com/monograph/ketotifen.html | title=Ketotifen Monograph for Professionals | access-date=16 November 2023 | archive-date=11 June 2021 | archive-url=https://web.archive.org/web/20210611120538/https://www.drugs.com/monograph/ketotifen.html | url-status=live }}</ref><ref name="monograph-ophtalmologic">{{cite web | url=https://www.drugs.com/mtm/ketotifen-ophthalmic.html | title=Ketotifen ophthalmic Uses, Side Effects & Warnings | access-date=16 November 2023 | archive-date=16 November 2023 | archive-url=https://web.archive.org/web/20231116205539/https://www.drugs.com/mtm/ketotifen-ophthalmic.html | url-status=live }}</ref><ref name="pediatric-ketotifen">{{cite web | url=https://www.pediatriconcall.com/drugs/ketotifen/689 | publisher=Pediatric Oncall | title=Ketotifen - Mechanism, Indication, Contraindications, Dosing, Adverse Effect, Interaction, Hepatic Dose; Drug Index; Pediatric Oncall | access-date=16 November 2023 | archive-date=16 November 2023 | archive-url=https://web.archive.org/web/20231116205541/https://www.pediatriconcall.com/drugs/ketotifen/689 | url-status=live }}</ref> whereas drug-eluting contact lenses are not recommended for children under eleven years of age.<ref name="dailymed-lens"/>

For oral ketotifen, the contraindication is for known hypersensitivity to any component of the product. Caution should be taken on the following conditions: [[acute porphyria]]s (a group of rare disorders that occur when the body cannot make enough of a substance called heme, which is needed for red blood cells to carry oxygen, this causes a build-up of chemicals called porphyrins, which can damage the nerves and the skin), [[epilepsy]] (a disorder causing recurrent seizures), [[prostatic hypertrophy]] (in adults), [[pyloroduodenal obstruction]]<ref>{{cite journal|date=29 September 2013|doi=10.12968/npre.2009.7.4.41711 |title=Antihistamines: Mode of action, prescribing rationale and uses |journal=Nurse Prescribing |volume=7 |issue=4 |pages=166–170 | vauthors = Waterfield J }}</ref><ref>{{cite journal|date=13 June 2011|doi=10.1002/psb.758 |title=Antihistamines: Their properties and use in hay fever |journal=Prescriber |volume=22 |issue=10 |pages=29–31 | vauthors = Chaplin S, Scadding G }}</ref><ref name="monograph-general"/> (a condition where the passage of food from the stomach to the small intestine is blocked by something, such as a muscle, an ulcer, a tumor, or a gallstone), susceptibility to [[angle-closure glaucoma]] (a condition where the iris, the colored part of the eye, bulges and blocks the drainage of fluid from the eye, causing high pressure and damage to the optic nerve, a nerve that connects the eye to the brain), and [[urinary retention]] (inability to urinate).<ref name="monograph-general"/>

The use of ketotifen eye drops during pregnancy and lactation is considered safe, as [[Absorption (pharmacology)|absorption]] through the eye is limited. It is unlikely to cause any adverse effects in breastfeeding infants after maternal use. To minimize the amount of medication transferred to breast milk when using eye drops, the [[National Institute of Child Health and Human Development]] advises to apply pressure on the [[tear duct]] near the corner of the eye for at least one minute and remove any excess solution with a tissue.<ref name="pmid30000587">{{cite book|id={{NCBIBook|NBK501527}}|pmid=30000587|title=Ketotifen|date=2006|url=https://www.ncbi.nlm.nih.gov/books/NBK501527|publisher=National Institute of Child Health and Human Development|access-date=22 November 2023|archive-date=3 October 2023|archive-url=https://web.archive.org/web/20231003214505/https://www.ncbi.nlm.nih.gov/books/NBK501527/|url-status=live}}</ref> Ketotifen safety when taken via the oral route (tablets or syrup) during pregnancy and lactation remains unknown; therefore, it is not recommended to use ketotifen orally during these periods until sufficient safety data becomes available.<ref name="pmid30000587"/>

==Side effects==

Common side effects of ophthalmic use are eye redness and [[Swelling (medical)|swelling]]. Less common are [[eye discharge]], eye discomfort, eye pain, [[hives]], increased [[itching]] of eyes, and rash. Ophthalmic use of ketotifen may also cause burning, stinging, or itching of the eyes, blurred vision, or increased sensitivity to light.<ref name="monograph-ophtalmologic"/>

Side effects of systemic (oral) use include [[drowsiness]], [[weight gain]] ({{convert|5.0|-|5.4|kg}}), [[dry mouth]], irritability, and increased [[nosebleed]]s.<ref name="www.mims.co.uk-2017">{{cite web|url=http://www.mims.co.uk/drugs/allergic-disorders/allergic-rhinitis-urticaria-other-allergies/zaditen|title=Zaditen - MIMS online|website=www.mims.co.uk|access-date=2 August 2017|archive-date=25 October 2020|archive-url=https://web.archive.org/web/20201025215920/https://www.mims.co.uk/drugs/allergic-disorders/allergic-rhinitis-urticaria-other-allergies/zaditen|url-status=live}}</ref> Systemic use of ketotifen may also cause abdominal pain, nausea, vomiting, constipation, diarrhea, headache, dizziness, or fatigue. In rare cases, systemic use of ketotifen may cause serious side effects such as [[anaphylaxis]], liver dysfunction, blood disorders, or seizures. Systemic use of ketotifen may interact with other drugs that cause sedation, such as [[Alcoholic beverage|alcohol]], antihistamines, [[opioid]]s, [[benzodiazepine]]s, or [[antidepressants]]. Systemic use of ketotifen may affect the results of some laboratory tests, such as skin tests for allergies or blood glucose levels.<ref name="pmid2226222">{{cite journal | vauthors = Grant SM, Goa KL, Fitton A, Sorkin EM | title = Ketotifen. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in asthma and allergic disorders | journal = Drugs | volume = 40 | issue = 3 | pages = 412–448 | date = September 1990 | pmid = 2226222 | doi = 10.2165/00003495-199040030-00006 | s2cid = 242916740 }}</ref>

==Overdose==

The symptoms of ketotifen overdose are dose-dependent and may vary from mild to severe. The onset of symptoms may be delayed for several hours after ingestion, and the duration of symptoms may last for more than 24 hours.<ref name="pmid1418695">{{cite journal | vauthors = Le Blaye I, Donatini B, Hall M, Krupp P | title = Acute ketotifen overdosage. A review of present clinical experience | journal = Drug Safety | volume = 7 | issue = 5 | pages = 387–392 | date = 1992 | pmid = 1418695 | doi = 10.2165/00002018-199207050-00007 | s2cid = 25839342 }}</ref><ref name="pmid6113023">{{cite journal | vauthors = Jeffreys DB, Volans GN | title = Ketotifen overdose: surveillance of the toxicity of a new drug | journal = British Medical Journal | volume = 282 | issue = 6278 | pages = 1755–1756 | date = May 1981 | pmid = 6113023 | pmc = 1505736 | doi = 10.1136/bmj.282.6278.1755 }}</ref><ref name="Reactions Weekly-1992">{{cite journal|doi=10.2165/00128415-199204220-00009 |title=ACE inhibitors |journal=Reactions Weekly |date=1992 |issue=422 |page=5 }}</ref>

The most common symptom of ketotifen overdose is significant [[sedation]]. Other symptoms may include confusion, disorientation, agitation, [[hallucination]]s, [[ataxia]] (impairment of voluntary muscle movement), [[tremor]] (involuntary regular muscle contraction), [[myoclonus]] (involuntary, irregular muscle twitch), [[nystagmus]] (dysfunction of eye movement), [[dysarthria]] (poor speech), and [[slurred speech]].<ref name="pmid1418695"/><ref name="pmid6113023"/><ref name="Reactions Weekly-1992"/>

Other symptoms of ketotifen overdose may include [[tachycardia]] (fast, pounding, or irregular heartbeat or pulse), [[hypotension]] (low blood pressure), [[convulsion]]s, hyperexcitability (particularly in children), reversible coma, unusual tiredness or weakness, [[blurred vision]], dizziness or fainting, loss of consciousness.<ref name="pmid6113023"/><ref name="Reactions Weekly-1992"/>

The symptoms of ketotifen overdose may be described according to the affected system of the body. The cardiovascular effects of ketotifen overdose may include tachycardia, hypotension, arrhythmias, and [[cardiac arrest]]. The respiratory effects may include respiratory depression, [[sleep apnea]], and [[pulmonary edema]]. The gastrointestinal effects may include nausea, vomiting, abdominal pain, diarrhea, and [[pancreatitis]]. The renal effects may include [[acute renal failure]] and [[urinary retention]]. The hepatic effects may include [[hepatitis]] and [[jaundice]]. The hematologic effects may include [[anemia]], [[leukopenia]], [[thrombocytopenia]], and [[coagulopathy]]. The neurologic effects of ketotifen overdose may include [[convulsion]]s, hyperexcitability, [[coma]], and death. The risk of seizures is higher in children, especially those with a history of epilepsy or [[febrile seizure]]s. The risk of coma and death is higher in adults, especially those with pre-existing medical conditions or concomitant use of other drugs that cause sedation or lower the seizure threshold.<ref name="pmid1418695"/><ref name="pmid6113023"/>

In children, ketotifen overdose may lead to toxic encephalopathy with lifelong health consequences. There was a reported case of an overdose in a 4-month-old boy that led to growth retardation and mental deterioration.<ref name="pmid23279031">{{cite journal |doi=10.1111/j.1442-200X.2012.03718.x |url=https://www.proquest.com/openview/95fc56e245cc55e5f0fcb6a7f075f1fe |title=Ketotifen overdose. Toxic encephalopathy, epilepsy and mental retardation in an infant: case report |date=2012 |pmid=23279031 |quote=In the present case, a 4-month-old boy was administered ketotifen at 5 times the recommended dose, and he showed mental deterioration and growth retardation. The presence of developmental deterioration strongly suggests that overdose of ketotifen induces toxic encephalopathy. |journal=Pediatrics International |volume=54 |issue=6 |page=963 |vauthors=Yokoyama H, Hirose M, Uematsu M, Haginoya K, Iinuma K, Kimura S |access-date=3 April 2024 |archive-date=13 April 2024 |archive-url=https://web.archive.org/web/20240413010243/https://www.proquest.com/openview/95fc56e245cc55e5f0fcb6a7f075f1fe |url-status=live }}</ref><ref name="Reactions Weekly-2013">{{cite journal|doi=10.1007/s40278-013-2459-5 |title=Ketotifen overdose |journal=Reactions Weekly |date=2013 |volume=1447 |page=25 }}</ref><ref name="Reactions Weekly-1992"/>

== Interactions ==

In systemic (oral) administration, ketotifen has the potential to enhance the effects of sedatives, hypnotics, antihistamines, and alcohol. Interactions have been observed between oral ketotifen and oral [[hypoglycemic agents]], antihistamines, and medications with sedative properties.<ref name="Ketotifen-2mg-Tablets-2022">{{cite web |url=https://www.hsa.gov.sg/docs/default-source/announcements/reclassified-medicines/patient-information-leaflets/ketotifen-oral-tablets-and-solution-pil-20-05-2017.pdf |title=Ketotifen 2mg Tablets, 1mg/5mL Oral Solution (product monograph) |access-date=11 March 2024 |archive-date=18 July 2022 |archive-url=https://web.archive.org/web/20220718184521/https://www.hsa.gov.sg/docs/default-source/announcements/reclassified-medicines/patient-information-leaflets/ketotifen-oral-tablets-and-solution-pil-20-05-2017.pdf |url-status=live }}</ref><ref name="Ketotifen-1mg-Tablets-2024">{{cite web |url=https://pdf.hres.ca/dpd_pm/00067932.PDF |title=Tablets, 1 mg ketotifen (as ketotifen hydrogen fumarate), Oral (product monograph) |access-date=11 March 2024 |archive-date=21 February 2024 |archive-url=https://web.archive.org/web/20240221141530/https://pdf.hres.ca/dpd_pm/00067932.PDF |url-status=live }}</ref>

Oral ketotifen may interact with [[amphetamine]] and [[benzphetamine]], which may decrease the activities of ketotifen.<ref name="pmid6123414">{{cite journal | vauthors = Greenwood C | title = The pharmacology of ketotifen | journal = Chest | volume = 82 | issue = 1 Suppl | pages = 45S–48S | date = July 1982 | pmid = 6123414 | doi = 10.1378/chest.82.1_supplement.45s }}</ref><ref name="pmid7335554">{{cite journal | vauthors = Rogóz Z, Skuza G, Sowińska H | title = Central action of ketotifen | journal = Polish Journal of Pharmacology and Pharmacy | volume = 33 | issue = 5 | pages = 503–515 | date = 1981 | pmid = 7335554 | doi = }}</ref>

The concomitant use of oral ketotifen with [[amifampridine]], [[bupropion]], [[donepezil]], and [[pitolisant]], is not recommended.<ref name="Ketotifen-Oral-Adv-2023">{{cite web |url=https://www.drugs.com/cons/ketotifen-oral.html |title=Ketotifen (Oral) Advanced Patient Information |access-date=11 March 2024 |archive-date=2 December 2023 |archive-url=https://web.archive.org/web/20231202143424/https://www.drugs.com/cons/ketotifen-oral.html |url-status=live }}</ref>

In rare instances, patients who have been administered oral ketotifen with oral antidiabetic agents have exhibited a reversible decrease in thrombocyte count. As such, it is recommended to monitor [[thrombocyte]] counts in patients who are concurrently taking oral antidiabetic agents.<ref name="Ketotifen-2mg-Tablets-2022"/><ref name="Ketotifen-1mg-Tablets-2024"/>

Systemic use of ketotifen may decrease the effectiveness of [[benzylpenicilloyl polylysine]] as a diagnostic agent.<ref name="pmid6123414"/> Ketotifen may affect the results of some laboratory tests, such as skin tests for allergies or blood glucose levels. Ketotifen may interfere with the skin test reactions by suppressing the histamine response, leading to false-negative results.<ref name="pmid6123414"/>

Ophthalmic use of ketotifen may interact with contact lenses, as the eye drops may contain preservatives that can be absorbed by soft contact lenses and cause eye irritation.<ref name=rxlistophtalmic>{{cite web | url=https://www.rxlist.com/ketotifen_ophthalmic/generic-drug.htm | title=Ketotifen Ophthalmic: Generic, Uses, Side Effects, Dosages, Interactions, Warnings | access-date=1 December 2023 | archive-date=24 February 2024 | archive-url=https://web.archive.org/web/20240224233556/https://www.rxlist.com/ketotifen_ophthalmic/generic-drug.htm | url-status=live }}</ref>

==Pharmacology==

Ketotifen is a [[binding selectivity|selective]] [[antihistamine]] – that is, an [[inverse agonist]] of the [[histamine]] [[H1 receptor|H₁ receptor]] (K_i = 0.166&nbsp;nM)<ref name="pmid9165365">{{cite journal | vauthors = Kakiuchi M, Ohashi T, Musoh K, Kawamura K, Morikawa K, Kato H | title = Studies on the novel antiallergic agent HSR-609: its penetration into the central nervous system in mice and guinea pigs and its selectivity for the histamine H1-receptor | journal = Japanese Journal of Pharmacology | volume = 73 | issue = 4 | pages = 291–298 | date = April 1997 | pmid = 9165365 | doi = 10.1254/jjp.73.291 | doi-access = free | title-link = doi }}</ref> – and [[mast cell stabilizer]].<ref name="pmid36891173">{{cite journal |vauthors=Ma C, Li H, Lu S, Li X, Wang S, Wang W |title=Tryptase and Exogenous Trypsin: Mechanisms and Ophthalmic Applications |journal=J Inflamm Res |volume=16 |issue= |pages=927–939 |date=2023 |pmid=36891173 |pmc=9987324 |doi=10.2147/JIR.S402900 |doi-access=free | title-link=doi }}</ref><ref name="LemkeWilliams2008">{{cite book| vauthors = Nelson WL | chapter = Antihistamines and Related Antiallergic and Antiulcer Agents | veditors = Lemke TL, Williams DA |title=Foye's Principles of Medicinal Chemistry| chapter-url=https://books.google.com/books?id=R0W1ErpsQpkC&pg=PA1019|year=2008|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-6879-5|pages=1019–}}</ref><ref name="pmid25370135">{{cite journal | vauthors = Ang DC, Hilligoss J, Stump T | title = Mast Cell Stabilizer (Ketotifen) in Fibromyalgia: Phase 1 Randomized Controlled Clinical Trial | journal = The Clinical Journal of Pain | volume = 31 | issue = 9 | pages = 836–842 | date = September 2015 | pmid = 25370135 | pmc = 4417653 | doi = 10.1097/AJP.0000000000000169 }}</ref> By preventing the degranulation of mast cells, ketotifen inhibits the release of inflammatory mediators such as histamine and [[leukotriene]]s, which are implicated in allergic reactions.<ref name="pmid36891173"/> Ketotifen action is also based on its inhibition of serotonin release.<ref name="pmid36891173"/>

Ketotifen also plays a role in the prevention of accumulation of eosinophils, which are white blood cells that become active during allergic reactions and infections; as such, ketotifen helps in reducing inflammation this way.<ref name="pmid36891173"/>

In addition, ketotifen has weak [[anticholinergic]] (K_i = 204&nbsp;nM for {{abbrlink|mACh|muscarinic acetylcholine receptor}}) and [[antiserotonergic]] (K_i = 38.9&nbsp;nM for [[5-HT2A receptor|5-HT_2A]]) activity.<ref name="pmid9165365" /><ref name="Alagarsamy2012">{{cite book| vauthors = Alagarsamy V | chapter = Antihistamines | title=Textbook of Medicinal Chemistry Vol II - E-Book| chapter-url = https://books.google.com/books?id=0FPCuckMacAC&pg=PA38|date=16 June 2012|publisher=Elsevier Health Sciences|isbn=978-81-312-3259-0|pages=38–}}</ref> However, at the dosages in which it is typically used clinically, both the anticholinergic and antiserotonergic activity of ketotifen are said not to be appreciable.<ref name="Drews2012">{{cite book| vauthors = Drews J | chapter = Substances with an Antialergic Effect |title=Immunopharmacology: Principles and Perspectives| chapter-url = https://books.google.com/books?id=mIN9CAAAQBAJ&pg=PT282|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-75561-3|pages=282–}}</ref>

Ketotifen is a [[Lipophilicity|lipophilic compound]] that can cross the [[blood–brain barrier]] and exert central nervous system effects, such as sedation,<ref name="pmid35538735"/> weight gain, and anticonvulsant activity. Ketotifen also has peripheral effects, such as inhibition of platelet aggregation, modulation of cytokine production, and enhancement of [[mucociliary clearance]].<ref name="pmid2226222"/><ref name="pmid31470575">{{cite journal |vauthors=Muñoz-Cano RM, Casas-Saucedo R, Valero Santiago A, Bobolea I, Ribó P, Mullol J |title=Platelet-Activating Factor (PAF) in Allergic Rhinitis: Clinical and Therapeutic Implications |journal=J Clin Med |volume=8 |issue=9 |date=August 2019 |page=1338 |pmid=31470575 |pmc=6780525 |doi=10.3390/jcm8091338 |doi-access=free | title-link=doi }}</ref><ref name="pmid8737746">{{cite journal |vauthors=Kahhak L, Roche A, Dubray C, Arnoux C, Benveniste J |title=Decrease of ciliary beat frequency by platelet activating factor: protective effect of ketotifen |journal=Inflamm Res |volume=45 |issue=5 |pages=234–8 |date=May 1996 |pmid=8737746 |doi=10.1007/BF02259609 }}</ref>

Ketotifen acts as a mast cell stabilizer by preventing the [[degranulation]] and release of histamine and other inflammatory mediators, such as [[leukotriene]]s,<ref name="pmid31118754"/> [[prostaglandin]]s, and [[cytokine]]s, from [[mast cell]]s. Ketotifen also inhibits the activation and migration of [[eosinophil]]s, [[basophil]]s, and [[neutrophil]]s, which are involved in the inflammatory response and tissue damage in allergic and respiratory diseases.<ref name="pmid23525348">{{cite journal |vauthors=Luna-Gomes T, Bozza PT, Bandeira-Melo C |title=Eosinophil recruitment and activation: the role of lipid mediators |journal=Front Pharmacol |volume=4 |issue= |pages=27 |date=2013 |pmid=23525348 |pmc=3605515 |doi=10.3389/fphar.2013.00027 |doi-access=free | title-link=doi }}</ref><ref name="pmid1702263"/><ref name="pmid12515585">{{cite journal |vauthors=Martín AP, Urrets-Zavalia J, Berra A, Mariani AL, Gallino N, Gomez Demel E, Gagliardi J, Baena-Cagnani CE, Urrets-Zavalia E, Serra HM |title=The effect of ketotifen on inflammatory markers in allergic conjunctivitis: an open, uncontrolled study |journal=BMC Ophthalmol |volume=3 |issue= |pages=2 |date=January 2003 |pmid=12515585 |pmc=140320 |doi=10.1186/1471-2415-3-2 |doi-access=free | title-link=doi }}</ref>

Ketotifen has a dual mode of action as an antihistamine and a [[mast cell stabilizer]], which makes it effective in the prophylaxis and treatment of various allergic and respiratory conditions, such as asthma, allergic rhinitis, conjunctivitis,<ref name="pmid36816214"/> dermatitis, urticaria, and anaphylaxis. Ketotifen can also reduce the [[bronchial hyperreactivity]] and airway inflammation that are characteristic of [[Asthma|chronic asthma]].<ref name="Stone-2014">{{cite book|doi=10.1007/978-1-4614-9194-1_242|chapter=Oral Mast Cell Stabilizers|date=1 January 2014 |title=Encyclopedia of Medical Immunology |pages=551–555 |isbn=978-1-4614-9193-4 | vauthors = Stone M, Francisco JC, Kumar NN, Barboza J }}</ref><ref name="pmid24267353"/><ref name="pmid12515585"/>

Ketotifen has [[plasma half-life]] of about 12 hours. Ketotifen is extensively metabolized in the liver by oxidation and conjugation, and the metabolites are excreted in the urine and feces. The bioavailability of oral ketotifen is about 50% due to hepatic first-pass metabolism. Peak plasma concentration is reached in about 2 to 4 hours. The pharmacokinetics of ketotifen are not significantly affected by age, gender, or renal impairment, but may be altered by hepatic impairment or concomitant use of other drugs.<ref name="pmid23713715">{{cite journal |vauthors=Fahmy RH, Badr-Eldin SM |title=Novel delivery approach for ketotifen fumarate: dissofilms formulation using 3² experimental design: in vitro/in vivo evaluation |journal=Pharm Dev Technol |volume=19 |issue=5 |pages=521–30 |date=August 2014 |pmid=23713715 |doi=10.3109/10837450.2013.800108 |s2cid=45012360 }}</ref>

Ketotifen, like other antihistamines,<ref name="pmid35538735">{{cite journal |vauthors=Li L, Liu R, Peng C, Chen X, Li J |title=Pharmacogenomics for the efficacy and side effects of antihistamines |journal=Exp Dermatol |volume=31 |issue=7 |pages=993–1004 |date=July 2022 |pmid=35538735 |doi=10.1111/exd.14602}}</ref><ref name="pmid11764306">{{cite journal |vauthors=Merk HF |title=Standard treatment: the role of antihistamines |journal=J Investig Dermatol Symp Proc |volume=6 |issue=2 |pages=153–6 |date=November 2001 |pmid=11764306 |doi=10.1046/j.0022-202x.2001.00032.x|doi-access=free | title-link=doi }}</ref> is mainly metabolized by the [[Cytochrome P450|cytochrome P450 (CYP) enzymes]], especially [[CYP3A4]]<ref name="El-Kommos-2015">{{cite journal | doi=10.1016/j.ancr.2014.11.003 | title=Analysis for commonly prescribed non-sedating antihistamines | date=2015 | journal=Analytical Chemistry Research | volume=3 | pages=1–12 | vauthors = El-Kommos ME, El-Gizawy SM, Atia NN, Hosny NM | doi-access=free }}</ref><ref name="pmid17357376">{{cite journal |vauthors=Jáuregui I, Mullol J, Bartra J, del Cuvillo A, Dávila I, Montoro J, Sastre J, Valero AL |title=H1 antihistamines: psychomotor performance and driving |journal=J Investig Allergol Clin Immunol |volume=16 |issue= Suppl 1|pages=37–44 |date=2006 |pmid=17357376}}</ref> in the liver. The CYP enzymes are responsible for the oxidation and demethylation of ketotifen, producing the major metabolites [[norketotifen]] and [[10-hydroxyketotifen]]. Norketotifen is pharmacologically active and has a similar potency as ketotifen, while [[10-hydroxyketotifen]] is inactive. The metabolites are then conjugated with [[glucuronic acid]] or sulfate and excreted in the urine and feces.<ref name="Lieberman-2008">{{cite book | chapter-url=https://doi.org/10.1016/B978-0-323-04404-2.10089-2 | doi=10.1016/B978-0-323-04404-2.10089-2 | chapter=Antihistamines | title=Clinical Immunology | date=2008 | pages=1317–1329 | isbn=978-0-323-04404-2 | vauthors=Lieberman P, Hernandez-Trujillo V, Lieberman J, Frew AJ | access-date=14 February 2024 | archive-date=24 February 2024 | archive-url=https://web.archive.org/web/20240224233628/https://www.sciencedirect.com/science/article/abs/pii/B9780323044042100892?via%3Dihub | url-status=live }}</ref><ref name="CDER-app-21-066">{{cite web |url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/21-066_ZADITOR%200.025%25_pharmr_P1.pdf |title=Center for drug evaluation and research. Application no. 21-066|access-date=14 February 2024 |archive-date=14 February 2024 |archive-url=https://web.archive.org/web/20240214190040/https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/21-066_ZADITOR%200.025%25_pharmr_P1.pdf |url-status=live }}</ref>

==Classification==

[[Image:Pizotifen_structure.svg|right|thumb|upright=0.75|Chemical structure of a [[pizotifen]], a [[tricyclic]] (having three rings of atoms), [[benzocycloheptene]]-based compound with antihistamine properties and the structure similar to that of ketotifen: the only difference is that ketotifen molecule has an oxygen atom that pizotifen molecule lacks—ketotifen contains a carbonyl group (C=O) in the central (7-membered) ring while pizotifen contains methylene group (-CH₂-) in that position. In both ketotifen and pizotifen, the spatial restriction and reduced degrees of freedom caused by the rings enable optimal binding to H₁ receptors by providing shape complementarity and facilitating specific interactions with amino acid residues within the receptor's binding site, which plays a role in the ability of both drugs to effectively bind and modulate H₁ receptors, thereby exerting its antihistamine effects.<ref name="pmid1377628">{{cite journal|doi=10.1016/0014-2999(92)90383-F |title=Affinity profiles of pizotifen, ketotifen and other tricyclic antimuscarinics at muscarinic receptor subtypes M1, M2 and M3 |date=1992 |journal=European Journal of Pharmacology |volume=211 |issue=3 |pages=283–293 |pmid=1377628 |vauthors=Eltze M, Mutschler E, Lambrecht G }}</ref>]]

Ketotifen is a [[H1 antihistamine|noncompetitive H₁-antihistamine]] and [[mast cell stabilizer]].<ref name="pmid34335590">{{cite journal |vauthors=Sarcina D, Giovannini M, Oranges T, Barni S, Pedaci FA, Liccioli G, Canessa C, Sarti L, Lodi L, Filippeschi C, Azzari C, Ricci S, Mori F |title=Case Report and Review of the Literature: Bullous Skin Eruption After the Booster-Dose of Influenza Vaccine in a Pediatric Patient With Polymorphic Maculopapular Cutaneous Mastocytosis |journal=Front Immunol |volume=12 |year=2021 |pmid=34335590 |pmc=8322976 |doi=10.3389/fimmu.2021.688364|doi-access=free | title-link=doi }}</ref>

There is no academic consensus on whether ketotifen should be classified as a medication belonging to the first<ref name="pmid30779379">{{cite journal | vauthors = Bittner L, Teixidó E, Keddi I, Escher BI, Klüver N | title = pH-Dependent Uptake and Sublethal Effects of Antihistamines in Zebrafish (Danio rerio) Embryos | journal = Environmental Toxicology and Chemistry | volume = 38 | issue = 5 | pages = 1012–1022 | date = May 2019 | pmid = 30779379 | doi = 10.1002/etc.4395 | s2cid = 73482611 }}</ref><ref name="pmid31463682">{{cite journal | vauthors = Pinke KH, Zorzella-Pezavento SF, de Campos Fraga-Silva TF, Mimura LA, de Oliveira LR, Ishikawa LL, Fernandes AA, Lara VS, Sartori A | title = Calming Down Mast Cells with Ketotifen: A Potential Strategy for Multiple Sclerosis Therapy? | journal = Neurotherapeutics | volume = 17 | issue = 1 | pages = 218–234 | date = January 2020 | pmid = 31463682 | pmc = 7007452 | doi = 10.1007/s13311-019-00775-8 }}</ref><ref name="pmid24267353">{{cite journal | vauthors = Sokol KC, Amar NK, Starkey J, Grant JA | title = Ketotifen in the management of chronic urticaria: resurrection of an old drug | journal = Annals of Allergy, Asthma & Immunology | volume = 111 | issue = 6 | pages = 433–436 | date = December 2013 | pmid = 24267353 | pmc = 4309375 | doi = 10.1016/j.anai.2013.10.003 }}</ref> or the second generations of antihistamine drugs;<ref name="pmid34387278">{{cite journal | vauthors = Janeczko P, Norris MR, Bielory L | title = Assessment of receptor affinities of ophthalmic and systemic agents in dry eye disease | journal = Current Opinion in Allergy and Clinical Immunology | volume = 21 | issue = 5 | pages = 480–485 | date = October 2021 | pmid = 34387278 | doi = 10.1097/ACI.0000000000000773 | s2cid = 236998913 }}</ref><ref name="pmid32086998">{{cite journal | vauthors = Triantafillou V, Maina IW, Patel NN, Tong CC, Papagiannopoulos P, Kohanski MA, Kennedy DW, Palmer JN, Adappa ND, Cohen NA, Bosso JV | title = In vitro safety of ketotifen as a topical nasal rinse | journal = International Forum of Allergy & Rhinology | volume = 10 | issue = 2 | pages = 265–270 | date = February 2020 | pmid = 32086998 | doi = 10.1002/alr.22461 | s2cid = 211246051 }}</ref> the classification can vary depending on the criteria used and the context of the study,<ref name="pmid9951950"/> and is primarily based on chemical structure, pharmacological properties, and side effect profiles of an antihistamine drug.<ref name="pmid37815801"/><ref name="pmid9951950"/><ref name="pmid2226222"/><ref name="pmid9759694"/> First-generation H₁ antihistamines, such as diphenhydramine, reduce skin reactivity for up to 24 hours, whereas ketotifen suppresses skin reactivity for over five days, a typical duration for the second generation of the class.<ref name="Chiriac-2017">{{cite book | chapter-url=https://doi.org/10.1016/B978-0-323-37579-5.00005-2 | doi=10.1016/B978-0-323-37579-5.00005-2 | chapter=Principles of Allergy Diagnosis | title=Middleton's Allergy Essentials | date=2017 | pages=117–131 | isbn=978-0-323-37579-5 | vauthors=Chiriac AM, Bousquet J, Demoly P | access-date=14 February 2024 | archive-date=24 February 2024 | archive-url=https://web.archive.org/web/20240224233608/https://www.sciencedirect.com/science/article/abs/pii/B9780323375795000052?via%3Dihub | url-status=live }}</ref> Ketotifen is a [[tricyclic]], [[benzocycloheptene]]-based compound with chemical structures similar to first-generation antihistamines such as [[azatadine]], [[cyproheptadine]], [[chlorpheniramine]] and [[diphenhydramine]], and other compounds with antihistamine properties such as [[pizotifen]]. The sedative effects of ketotifen is also a reason in differences in classification. First-generation antihistamines are well known for their sedating side effects due to their ability to penetrate the [[blood–brain barrier]].<ref name="pmid37815801">{{cite journal | vauthors = Sagara A, Nagahama A, Aki H, Yoshimura H, Hiraide M, Shimizu T, Sano M, Yumoto T, Hosoe T, Tanaka K | title = Potential risk of driving performance under combined conditions of taking second-generation antihistamines and attending calls using a hands-free function | journal = Traffic Injury Prevention | volume = 25 | issue = 1 | pages = 36–40 | date = October 2023 | pmid = 37815801 | doi = 10.1080/15389588.2023.2265002 | s2cid = 263801715 }}</ref> While ketotifen has some sedative properties, it is generally considered to have a milder sedative effect compared to traditional first-generation antihistamines,<ref name="pmid9951950">{{cite journal | vauthors = Slater JW, Zechnich AD, Haxby DG | title = Second-generation antihistamines: a comparative review | journal = Drugs | volume = 57 | issue = 1 | pages = 31–47 | date = January 1999 | pmid = 9951950 | doi = 10.2165/00003495-199957010-00004 | s2cid = 24659435 }}</ref><ref name="pmid2226222"/> so this reduced sedation is one of the reasons why ketotifen is sometimes classified as a second-generation antihistamine.<ref name="pmid9759694">{{cite journal | vauthors = Aelony Y | title = First-generation vs second-generation antihistamines | journal = Archives of Internal Medicine | volume = 158 | issue = 17 | pages = 1949–1950 | date = September 1998 | pmid = 9759694 | doi = 10.1001/archinte.158.17.1949 }}</ref>

== History ==

Ketotifen was patented in 1970 and came into medical use in 1976.<ref name=Fis2006>{{cite book |vauthors=Alapi EM, Fischer J |chapter=Table of Selected Analogue Classes |veditors=Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=978-3-527-60749-5 |page=548 |chapter-url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA548 |access-date=1 August 2020 |archive-date=10 January 2023 |archive-url=https://web.archive.org/web/20230110031314/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA548 |url-status=live }}</ref> Ketotifen was developed and patented by [[Sandoz Pharmaceuticals]] (currently a part of [[Novartis]]), a Swiss company.<ref name="Drugbank-2024">{{cite web|url=https://go.drugbank.com/drugs/DB00920|title=Ketotifen|date=12 April 2024|publisher=[[Drugbank]]|access-date=16 November 2023|archive-date=6 August 2019|archive-url=https://web.archive.org/web/20190806095438/https://www.drugbank.ca/drugs/DB00920|url-status=live}}</ref><ref name="Inxight Drugs-2024">{{cite web|url=https://drugs.ncats.io/drug/HBD503WORO|title=Ketotifen Fumarate|date=12 April 2024|website=Inxight Drugs|publisher=National Center for Advancing Translational Sciences (NCATS)|location=Bethesda MD, US|access-date=13 April 2024|archive-date=13 April 2024|archive-url=https://web.archive.org/web/20240413010346/https://drugs.ncats.io/drug/HBD503WORO|url-status=live}}</ref><ref name="pmid6806019">{{cite journal |url=https://journal.chestnet.org/article/S0012-3692(15)33591-1/abstract |doi=10.1378/chest.82.1.30S |title=An Overview of Ketotifen |date=1982 |journal=Chest |volume=82 |issue=1 Suppl |pages=30s–32s |pmid=6806019 |vauthors=MacDonald G |access-date=13 April 2024 |archive-date=13 April 2024 |archive-url=https://web.archive.org/web/20240413010421/https://journal.chestnet.org/article/S0012-3692(15)33591-1/abstract |url-status=live |url-access=subscription }}</ref>

Ketotifen was approved for medical use in Canada in December 1990.<ref name="Zaditen CA PI" /> Ketotifen was approved for medical use in the United States in July 1999.<ref name="accessdata.fda.gov-2001">{{cite web | title=Drug Approval Package: Zaditor (Ketotifen Fumarate) NDA# 21-066 | website=accessdata.fda.gov | date=20 November 2001 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/21-066_Zaditor.cfm | access-date=10 March 2024 | archive-date=8 March 2024 | archive-url=https://web.archive.org/web/20240308064947/https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/21-066_Zaditor.cfm | url-status=live }}</ref> The contact lens with ketotifen was approved for medical use in the United States in 2022.<ref name="accessdata.fda.gov-2022">{{cite web | title=Drug Approval Package: Acuvue Theravision with ketotifen | website=accessdata.fda.gov | date=19 September 2022 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2022/022388Orig1s000TOC.cfm | access-date=10 March 2024 | archive-date=10 March 2024 | archive-url=https://web.archive.org/web/20240310191328/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2022/022388Orig1s000TOC.cfm | url-status=live }}</ref><ref name="Johnson-2022">{{cite press release | title=Johnson & Johnson Vision Care Receives FDA Approval for Acuvue Theravision with Ketotifen – World's First and Only Drug-Eluting Contact Lens | website=Johnson and Johnson Vision | date=2 March 2022 | url=https://www.jjvision.com/press-release/johnson-johnson-vision-care-receives-fda-approval-acuvuer-theravisiontm-ketotifen | access-date=10 March 2024 | archive-date=11 March 2024 | archive-url=https://web.archive.org/web/20240311114818/https://www.jjvision.com/press-release/johnson-johnson-vision-care-receives-fda-approval-acuvuer-theravisiontm-ketotifen | url-status=live }}</ref>

== Society and culture ==

[[File:Ketotifen-generic-sopharma.jpg|thumb|right|A generic formulation of ketotifen marketed under the Ketotifen Sopharma brand name]]

=== Economics ===

In 2021, it was the 301st most commonly prescribed medication in the United States, with more than {{Val|400000}} prescriptions.<ref name="ClinCalc-2023">{{cite web | title = Ketotifen - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Ketotifen | access-date = 14 January 2024 | archive-date = 4 June 2023 | archive-url = https://web.archive.org/web/20230604012216/https://clincalc.com/DrugStats/Drugs/Ketotifen | url-status = live }}</ref>

=== Brand names ===

Ketotifen is sold under various brand names worldwide, depending on country and formulation, with over 200 different names used.<ref name="Ketotifen-International">{{cite web | title=Ketotifen International | website=Drugs.com | url=https://www.drugs.com/international/ketotifen.html | access-date=4 September 2020 | archive-date=11 April 2021 | archive-url=https://web.archive.org/web/20210411134835/https://www.drugs.com/international/ketotifen.html | url-status=live }}</ref><ref name="MSN">{{cite web | url=https://www.msn.com/en-in/health/wellness/what-to-know-about-ketotifen-popular-brands-ketasma-and-asthafen/ar-BB1kFqmx | website=[[MSN]] | title=What To Know About Ketotifen (popular Brands: Ketasma And Asthafen) | author=Tata | date=28 March 2024 | access-date=2 April 2024 | archive-date=13 April 2024 | archive-url=https://web.archive.org/web/20240413010153/https://www.msn.com/en-in/health/wellness/what-to-know-about-ketotifen-popular-brands-ketasma-and-asthafen/ar-BB1kFqmx | url-status=live }}</ref><ref name="Ketotifen-Ingredient">{{cite web |url=https://www.drugs.com/ingredient/ketotifen.html |title=Ketotifen (Ingredient) |access-date=2 April 2024 |archive-date=2 April 2024 |archive-url=https://web.archive.org/web/20240402191446/https://www.drugs.com/ingredient/ketotifen.html |url-status=live }}</ref> In the United States, ketotifen fumarate ophtalmic solution is marketed under brand name Zaditor, which is owned by [[Alcon|Alcon Inc.]], a Swiss-American pharmaceutical company.<ref name="European Medicines Agency-2018-2">{{cite web | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ac66b1e4-c2b0-a4c3-09e3-ebd44a2f7c9f | title=DailyMed - ZADITOR- ketotifen fumarate solution | access-date=5 September 2020 | archive-date=11 June 2021 | archive-url=https://web.archive.org/web/20210611120517/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ac66b1e4-c2b0-a4c3-09e3-ebd44a2f7c9f |publisher=National Institutes of Health| url-status=live | date=15 December 2023}}</ref><ref name="Ketotifen Update-2019-2">{{Cite web |title=Trademark search - ZADITOR|publisher=USPTO|date=8 April 2024|url=https://tsdr.uspto.gov/#caseNumber=75680062&caseSearchType=US_APPLICATION&caseType=DEFAULT&searchType=statusSearch |access-date=8 April 2024 |archive-date=13 July 2021 |archive-url=https://web.archive.org/web/20210713022850/https://tsdr.uspto.gov/#caseNumber=75680062&caseSearchType=US_APPLICATION&caseType=DEFAULT&searchType=statusSearch |url-status=live }}</ref>

=== Litigation ===

There was a litigation related to ketotifen. In 2021, the plaintiff, Edward C. Hanks, brought an action in the [[United States District Court for the Central District of Illinois]], against the defendants, Ned Hubbard and others, alleging that they violated his rights under the [[Eighth Amendment to the United States Constitution]] by acting with deliberate indifference to his serious medical needs. The plaintiff claimed that he suffered from a chronic eye condition that required medical attention and that the defendant, Dr. Hubbard, prescribed him ketotifen. The plaintiff further claimed that the ketotifen eye drops caused him adverse reactions, such as severe pain, burning, and blurred vision, and that the defendant, Dr. Hubbard, failed to offer him an alternative medication or refer him to an ophthalmologist. The plaintiff also claimed that he sustained permanent eye damage as a result of the ketotifen. The district court granted the defendant's motion to dismiss, finding that the plaintiff failed to state a claim upon which relief could be granted. The plaintiff appealed to the [[United States Court of Appeals for the Seventh Circuit]], which affirmed the district court's judgment on 7 February 2022.<ref name="Hanksv.Hubbard">{{cite court|litigants=Hanks v. Hubbard|court=C.D. Ill|date=8 March 2021}}</ref>

==Research==

===Norketotifen===

Research directions for ketotifen include the investigation of [[norketotifen]] (NK), a metabolite of ketotifen. [[In vitro]] studies using human [[liver]] [[microsome]]s and [[hepatocyte]]s suggest that NK may be the major [[Demethylation|demethylated]] hepatic metabolite of ketotifen. Unlike ketotifen, NK does not seem to induce severe sedative effects, potentially allowing for higher doses to be administered without sedation as a limiting factor. Furthermore, NK may probably have potent and dose-dependent inhibition of the release of the [[pro-inflammatory cytokine]] [[TNF-α]], suggesting potential [[anti-inflammatory]] activity. Thus, ketotifen can probably be considered a sedating [[prodrug]] that is converted to NK, a nonsedating [[metabolite]] with anti-inflammatory properties, when used as an anti-inflammatory medication.<ref name="pmid34410005">{{cite journal | vauthors = Aberg AK, Arulnesan N, Bolger GT, Ciofalo VB, Pucaj K, Walle K, Walle T | title = Ketotifen is a Prodrug. Norketotifen is the active metabolite | journal = Drug Development Research | volume = 83 | issue = 2 | pages = 362–367 | date = April 2022 | pmid = 34410005 | doi = 10.1002/ddr.21865 | s2cid = 237216445 }}</ref> The potential future applications of norketotifen are researched by Emergo Therapeutics, a US company.<ref name="A Phase 2b Double-2023">{{cite web | url=https://classic.clinicaltrials.gov/ct2/show/NCT04610047 | title=A Phase 2b Double-blind, Randomized, Placebo-controlled, Parallel-group Study of the Efficacy and Safety of Norketotifen (NKT) in the Treatment of Acute Uncomplicated Influenza-like Illness (ILI) | date=25 January 2023 | access-date=13 April 2024 | archive-date=13 April 2024 | archive-url=https://web.archive.org/web/20240413010149/https://classic.clinicaltrials.gov/ct2/show/NCT04610047 | url-status=live }}</ref><ref name="Efficacy and Safety of Norketotifen in Uncomplicated Influenza-2023">{{cite web | url=https://trialbulletin.com/lib/entry/ct-04610047 | title=Efficacy and Safety of Norketotifen in Uncomplicated Influenza-like Illness: Influenza Clinical | date=30 January 2023 | access-date=13 April 2024 | archive-date=13 April 2024 | archive-url=https://web.archive.org/web/20240413010157/https://trialbulletin.com/lib/entry/ct-04610047 | url-status=live }}</ref><ref name="Efficacy and Safety of Norketotifen in Uncomplicated Influenza-2023a">{{cite web|url=https://ichgcp.net/clinical-trials-registry/NCT04610047|title=Efficacy and Safety of Norketotifen in Uncomplicated Influenza-like Illness|date=25 January 2023|access-date=13 April 2024|archive-date=20 April 2024|archive-url=https://web.archive.org/web/20240420185814/https://ichgcp.net/clinical-trials-registry/NCT04610047|url-status=live}}</ref><ref name="Emergo finds midstage success in developing flu">{{cite web | url=https://www.bioworld.com/articles/392013-emergo-finds-midstage-success-in-developing-flu-fighter-norketotifen | title=Emergo finds midstage success in developing flu-fighter norketotifen + &#124; Bioworld &#124; BioWorld | access-date=13 April 2024 | archive-date=13 April 2024 | archive-url=https://web.archive.org/web/20240413010908/https://www.bioworld.com/articles/392013-emergo-finds-midstage-success-in-developing-flu-fighter-norketotifen | url-status=live }}</ref><ref name="Norketotifen in Influenza">{{Cite web |url=https://ichgcp.net/clinical-trials-registry/NCT04043923 |title=Norketotifen in Influenza -Like Illness - Clinical Trials Registry - ICH GCP |access-date=13 April 2024 |archive-date=13 April 2024 |archive-url=https://web.archive.org/web/20240413010904/https://ichgcp.net/clinical-trials-registry/NCT04043923 |url-status=live }}</ref>

===Conditions===

====Increased appetite and weight gain====

The underlying mechanisms of why ketotifen (similarly to other antihistamine drugs such as [[astemizole]], [[azelastine]])<ref name="pmid9951950"/> may increase appetite and lead to weight gain in some people, are not fully understood.<ref name="pmid9951950"/>

Different studies have shown conflicting results about the amount of weight gain caused by ketotifen. In one study ([[postmarketing surveillance]]),<ref name="pmid9951950"/> it was found that around 1 to 2 out of every 100 people who took the drug experienced weight gain, with adults gaining about {{convert|1|kg}} and children over the age of one gaining {{convert|2.8|-|3.3|kg}}. However, in another study,<ref name="www.mims.co.uk-2017"/> adults gained a higher amount of weight: {{convert|5.0|-|5.4|kg}}.<ref name="www.mims.co.uk-2017"/>

Ketotifen exhibits a chemical resemblance to [[pizotifen]], a substance known for its [[Appetite stimulant|appetite-stimulating]] properties.<ref name="pmid9951950"/> One proposed mechanism of the increase in appetite involves the inhibitory effect of ketotifen on the production of [[TNF-α]], which is a [[cytokine]] that plays a role in regulating energy metabolism. TNF-α can act directly on [[adipocyte]]s (fat cells) to regulate the release of [[leptin]]. Leptin is a hormone produced by [[adipose tissue]] and acts as a satiety signal by binding to receptors in the [[hypothalamus]], where it inhibits appetite. By reducing TNF-α production, ketotifen may lead to decreased leptin levels, reducing appetite control inhibition. Furthermore, ketotifen's influence on [[serotonin]] regulation could be involved in central serotonin [[disinhibition]]. Serotonin is known to have suppressant effects on appetite. It is suggested that ketotifen might cause a decrease in serotonin levels due to this regulatory influence. As a result, the decrease in serotonin function may lead to increased food intake tendency and heightened appetite. Still, these potential mechanisms have been hypothesized based on limited evidence.<ref name="pmid24409414">{{cite journal | vauthors = Habibi Asl B, Vaez H, Imankhah T, Hamidi S | title = Impact of caffeine on weight changes due to ketotifen administration | journal = Advanced Pharmaceutical Bulletin | volume = 4 | issue = 1 | pages = 83–89 | date = 2014 | pmid = 24409414 | pmc = 3885374 | doi = 10.5681/apb.2014.013 }}</ref> Studies on mice suggest that [[caffeine]]<ref name="pmid24409414"/> or [[citrus aurantifolia]] oil<ref name="pmid20623616">{{cite journal | vauthors = Asnaashari S, Delazar A, Habibi B, Vasfi R, Nahar L, Hamedeyazdan S, Sarker SD | title = Essential oil from Citrus aurantifolia prevents ketotifen-induced weight-gain in mice | journal = Phytotherapy Research | volume = 24 | issue = 12 | pages = 1893–1897 | date = December 2010 | pmid = 20623616 | doi = 10.1002/ptr.3227 | s2cid = 8888404 | url = https://hal.science/hal-00553269 | access-date = 10 January 2024 | archive-date = 28 January 2024 | archive-url = https://web.archive.org/web/20240128210538/https://hal.science/hal-00553269 | url-status = live }}</ref> may prevent weight-gain induced by ketotifen, but, this has not been confirmed on human subjects.<ref name="pmid20623616"/>

====Irritable bowel syndrome====

Ketotifen is currently researched in context of a possible link between abnormalities in intestinal mast cells and [[irritable bowel syndrome]], but there are no solid results yet.<ref name="pmid26755686">{{cite journal | vauthors = Zhang L, Song J, Hou X | title = Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside | journal = Journal of Neurogastroenterology and Motility | volume = 22 | issue = 2 | pages = 181–192 | date = April 2016 | pmid = 26755686 | pmc = 4819856 | doi = 10.5056/jnm15137 }}</ref><ref name="pmid20650926">{{cite journal | vauthors = Klooker TK, Braak B, Koopman KE, Welting O, Wouters MM, van der Heide S, Schemann M, Bischoff SC, van den Wijngaard RM, Boeckxstaens GE | title = The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome | journal = Gut | volume = 59 | issue = 9 | pages = 1213–1221 | date = September 2010 | pmid = 20650926 | doi = 10.1136/gut.2010.213108 | s2cid = 18889707 | url = https://pure.uva.nl/ws/files/1485582/95328_340461.pdf | access-date = 24 September 2019 | archive-date = 11 June 2021 | archive-url = https://web.archive.org/web/20210611120523/https://pure.uva.nl/ws/files/1485582/95328_340461.pdf | url-status = live }}</ref>

====COVID-19====

It was hypothesized that ketotifen may be effective against [[SARS-CoV-2]], a virus behind the [[COVID-19 pandemic]], but there were no studies to confirm the hypothesis; the research did not proceed behind ''[[in-vitro]]'' experiments.<ref name="pmid33810356">{{cite journal | vauthors = Kiani P, Scholey A, Dahl TA, McMann L, Iversen JM, Verster JC | title = In Vitro Assessment of the Antiviral Activity of Ketotifen, Indomethacin and Naproxen, Alone and in Combination, against SARS-CoV-2 | journal = Viruses | volume = 13 | issue = 4 | page = 558 | date = March 2021 | pmid = 33810356 | pmc = 8065848 | doi = 10.3390/v13040558 | doi-access = free | title-link = doi }}</ref>

{{clear}}

== References ==

{{Reflist}}

== External links ==

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