Ketotifen

Source: Wikipedia, the free encyclopedia.
Not to be confused with Ketoprofen, a nonsteroidal anti-inflammatory drug with analgesic and antipyretic effects.

Ketotifen
Clinical data
Trade namesZaditor,[1] Alaway, others
Other namesketotifen fumarate (USAN US)
AHFS/Drugs.comMonograph
MedlinePlusa604033
License data
Pregnancy
category
  • AU: B1
Routes of
administration		By mouth, eye drops, drug-eluting contact lenses
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability60%
Protein binding75%
MetabolismLiver
Elimination half-life12 hours
Identifiers
  • 4-(1-Methylpiperidin-4-ylidene)-4,9-dihydro-10H-benzo[4,5]cyclohepta[1,2-b]thiophen-10-one
JSmol)
  • O=C3c1sccc1C(\c2c(cccc2)C3)=C4/CCN(C)CC4
  • InChI=1S/C19H19NOS/c1-20-9-6-13(7-10-20)18-15-5-3-2-4-14(15)12-17(21)19-16(18)8-11-22-19/h2-5,8,11H,6-7,9-10,12H2,1H3 checkY
  • Key:ZCVMWBYGMWKGHF-UHFFFAOYSA-N checkY
  • Key:YNQQEYBLVYAWNX-WLHGVMLRSA-N
  (verify)

Ketotifen is an

food allergies
.

Ketotifen acts by blocking the

leukotriene antagonist, which blocks inflammation-causing chemicals known as leukotrienes; 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 porphyrias 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 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 with fumaric acid, ketotifen fumarate, and is available in two forms:[6]

  1. in its ophthalmic form (eye drops or drug-eluting contact lenses),[7][5][8] it is used to treat allergic conjunctivitis;[9][1]
  2. in its oral form (tablets or syrup),[6] it is used to prevent asthma attacks or anaphylaxis,[10][11] as well as various mast cell, allergic-type disorders.[12][13][14]

Ketotifen ophthalmic solution (eye drops) relieves and prevents eye itchiness and/or irritation associated with most 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,[1] whereas drug-eluting contact lenses have not been studied in children under eleven years old.[5]

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.[5]

Oral ketotifen is used to treat asthma,

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.[15][14][10] In patients with MCAS, ketotifen reduce episodes of 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.[16]

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.[14][10] However, ketotifen eye drops are approved in the US for people who are at least three years of age.[17][18] In the EU, ketotifen oral formulatios (syrup, tables and capsules) are approved by the European Medicines Agency for adult use.[19] In the UK, ketotifen is available as tables and elixir (liquid).[20]

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 bronchodilators, 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.[21]

The mean elimination half-life of ketotifen is 12 hours.[22] Besides its anti-histaminic activity, it is also a functional leukotriene antagonist[23] (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)[24][25] and a phosphodiesterase inhibitor[26][27] (a medication that blocks the enzymes that regulate the levels of cAMP and cGMP, which are molecules that control blood vessel dilation and smooth muscle relaxation in the body).[28][29]

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,[30][18][31] whereas drug-eluting contact lenses are not recommended for children under eleven years of age.[5]

For oral ketotifen, the contraindication is for known hypersensitivity to any component of the product. Caution should be taken on the following conditions:

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).[30]

The use of ketotifen eye drops during pregnancy and lactation is considered safe, as

tear duct near the corner of the eye for at least one minute and remove any excess solution with a tissue.[32] 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.[32]

Side effects

Common side effects of ophthalmic use are eye redness and

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.[18]

Side effects of systemic (oral) use include

antidepressants. Systemic use of ketotifen may affect the results of some laboratory tests, such as skin tests for allergies or blood glucose levels.[6]

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.[34][35][36]

The most common symptom of ketotifen overdose is significant

slurred speech.[34][35][36]

Other symptoms of ketotifen overdose may include tachycardia (fast, pounding, or irregular heartbeat or pulse), hypotension (low blood pressure), convulsions, hyperexcitability (particularly in children), reversible coma, unusual tiredness or weakness, blurred vision, dizziness or fainting, loss of consciousness.[35][36]

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

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 convulsions, hyperexcitability, coma, and death. The risk of seizures is higher in children, especially those with a history of epilepsy or febrile seizures. 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.[34][35]

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.[37][38][36]

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.[39][40]

Oral ketotifen may interact with amphetamine and benzphetamine, which may decrease the activities of ketotifen.[41][42]

The concomitant use of oral ketotifen with amifampridine, bupropion, donepezil, and pitolisant, is not recommended.[43]

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.[39][40]

Systemic use of ketotifen may decrease the effectiveness of benzylpenicilloyl polylysine as a diagnostic agent.[41] 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.[41]

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.[44]

Pharmacology

Ketotifen is a

H1 receptor (Ki = 0.166 nM)[45] – and mast cell stabilizer.[46][47][48] By preventing the degranulation of mast cells, ketotifen inhibits the release of inflammatory mediators such as histamine and leukotrienes, which are implicated in allergic reactions.[46] Ketotifen action is also based on its inhibition of serotonin release.[46]

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.[46]

In addition, ketotifen has weak

antiserotonergic (Ki = 38.9 nM for 5-HT2A) activity.[45][49] 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.[50]

Ketotifen is a lipophilic compound that can cross the blood-brain barrier and exert central nervous system effects, such as sedation,[51] 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.[6][52][53]

Ketotifen acts as a mast cell stabilizer by preventing the degranulation and release of histamine and other inflammatory mediators, such as leukotrienes,[23] prostaglandins, and cytokines, from mast cells. Ketotifen also inhibits the activation and migration of eosinophils, basophils, and neutrophils, which are involved in the inflammatory response and tissue damage in allergic and respiratory diseases.[54][27][55]

Ketotifen has a dual mode of action as an antihistamine and a

bronchial hyperreactivity and airway inflammation that are characteristic of chronic asthma.[56][12][55]

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.[57]

Ketotifen, like other antihistamines,[51][58] is mainly metabolized by the cytochrome P450 (CYP) enzymes, especially CYP3A4[59][60] 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.[61][62]

Classification

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.[63]

Ketotifen is a noncompetitive H1-antihistamine and mast cell stabilizer.[64]

There is no academic consensus on whether ketotifen should be classified as a medication belonging to the first

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.[70] While ketotifen has some sedative properties, it is generally considered to have a milder sedative effect compared to traditional first-generation antihistamines,[69][6] so this reduced sedation is one of the reasons why ketotifen is sometimes classified as a second-generation antihistamine.[71]

History

Ketotifen was patented in 1970 and came into medical use in 1976.

Sandoz Pharmaceuticals (currently a part of Novartis), a Swiss company.[74][75][76]

Ketotifen was approved for medical use in Canada in December 1990.[2] Ketotifen was approved for medical use in the United States in July 1999.[77] The contact lens with ketotifen was approved for medical use in the United States in 2022.[78][79]

Society and culture

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 400000 prescriptions.[80]

Brand names

Ketotifen is sold under various brand names worldwide, depending on country and formulation, with over 200 different names used.[81][82][83] In the United States, ketotifen fumarate ophtalmic solution is marketed under brand name Zaditor, which is owned by Alcon Inc., a Swiss-American pharmaceutical company.[84][85]

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.[86]

Research

Norketotifen

Research directions for ketotifen include the investigation of

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.[87] The potential future applications of norketotifen are researched by Emergo Therapeutics, a US company.[88][89][90][91][92]

Conditions

Increased appetite and weight gain

The underlying mechanisms of why ketotifen (similarly to other antihistamine drugs such as astemizole, azelastine)[69] may increase appetite and lead to weight gain in some people, are not fully understood.[69]

Different studies have shown conflicting results about the amount of weight gain caused by ketotifen. In one study (postmarketing surveillance),[69] it was found that around 1 to 2 out of every 100 people who took the drug experienced weight gain, with adults gaining about 1 kilogram (2.2 lb) and children over the age of one gaining 2.8–3.3 kilograms (6.2–7.3 lb). However, in another study,[33] adults gained a higher amount of weight: 5.0–5.4 kilograms (11.0–11.9 lb).[33]

Ketotifen exhibits a chemical resemblance to

citrus aurantifolia oil[94] may prevent weight-gain induced by ketotifen, but, this has not been confirmed on human subjects.[94]

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.[95][96]

COVID-19

It was hypothesized that ketotifen may be effective against

in-vitro experiments.[97]

References

  1. ^ a b c d "Zaditor- ketotifen fumarate solution". DailyMed. 13 February 2020. Archived from the original on 11 June 2021. Retrieved 4 September 2020.
  2. ^ a b "Zaditen Product information". Health Canada. 22 October 2009. Archived from the original on 10 March 2024. Retrieved 10 March 2024.
  3. ^ "Zaditor Product information". Health Canada. 22 October 2009. Archived from the original on 10 March 2024. Retrieved 10 March 2024.
  4. ^ "Zaditen Summary of Product Characteristics (SmPC)". emc. 13 October 2020. Archived from the original on 10 March 2024. Retrieved 10 March 2024.
  5. ^ a b c d e "Acuvue Theravision with ketotifen". DailyMed. 11 March 2022. Archived from the original on 3 December 2023.
  6. ^
    S2CID 242916740
    .
  7. PMID 36000122
    .
  8. S2CID 30634949
    .
  9. ^
    PMID 36816214
    .
  10. ^
    S2CID 14587946
    .
  11. ^ Li Z, Celestin J (23 February 2015). Ketotifen: A Role in the Treatment of Idiopathic Anaphylaxis. American Academy of Allergy, Asthma & Immunology Annual Meeting. Houston.
  12. ^
    PMID 24267353
    .
  13. doi:10.1016/j.ejmhg.2015.04.003
    .
  14. ^
    PMID 23282889
    .
  15. PMID 34238222
    .
  16. S2CID 5723622
    .
  17. ^ "Acuvue Theravision with ketotifen (etafilcon A drug-eluting contact lens with ketotifen), for ophthalmic use" (PDF). 2022. Archived (PDF) from the original on 8 March 2024. Retrieved 13 April 2024.
  18. ^ a b c "Ketotifen ophthalmic Uses, Side Effects & Warnings". Archived from the original on 16 November 2023. Retrieved 16 November 2023.
  19. ^ "List of nationally authorised medicinal products" (PDF). European Medicines Agency. 14 June 2018. Archived (PDF) from the original on 13 April 2024. Retrieved 13 April 2024.
  20. ^ "Ketotifen Update (4th December 2019)". 4 December 2019. Archived from the original on 29 November 2023. Retrieved 13 April 2024.
  21. PMID 14973969
    .
  22. S2CID 72293850
    .
  23. ^
    PMID 31118754
    . Ketotifen has a stronger effect on stabilizing MCs than sodium cromoglycate. This drug has antihistamine activity and is also a functional leukotriene antagonist
  24. ISBN 978-3-7643-8530-9
    .
  25. PMID 31135881
    .
  26. PMID 33918481
    .
  27. ^
    PMID 1702263
    .
  28. PMID 17307970
    .
  29. doi:10.1093/bjaceaccp/mkm039
    .
  30. ^ a b "Ketotifen Monograph for Professionals". Archived from the original on 11 June 2021. Retrieved 16 November 2023.
  31. ^ "Ketotifen - Mechanism, Indication, Contraindications, Dosing, Adverse Effect, Interaction, Hepatic Dose; Drug Index; Pediatric Oncall". Pediatric Oncall. Archived from the original on 16 November 2023. Retrieved 16 November 2023.
  32. ^
    NCBI NBK501527. Archived
    from the original on 3 October 2023. Retrieved 22 November 2023.
  33. ^ a b c "Zaditen - MIMS online". www.mims.co.uk. Archived from the original on 25 October 2020. Retrieved 2 August 2017.
  34. ^
    S2CID 25839342
    .
  35. ^
    PMID 6113023
    .
  36. ^
    doi:10.2165/00128415-199204220-00009
    .
  37. PMID 23279031. Archived
    from the original on 13 April 2024. Retrieved 3 April 2024. 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.
  38. doi:10.1007/s40278-013-2459-5
    .
  39. ^ a b "Ketotifen 2mg Tablets, 1mg/5mL Oral Solution (product monograph)" (PDF). Archived (PDF) from the original on 18 July 2022. Retrieved 11 March 2024.
  40. ^ a b "Tablets, 1 mg ketotifen (as ketotifen hydrogen fumarate), Oral (product monograph)" (PDF). Archived (PDF) from the original on 21 February 2024. Retrieved 11 March 2024.
  41. ^
    PMID 6123414
    .
  42. PMID 7335554
    .
  43. ^ "Ketotifen (Oral) Advanced Patient Information". Archived from the original on 2 December 2023. Retrieved 11 March 2024.
  44. ^ "Ketotifen Ophthalmic: Generic, Uses, Side Effects, Dosages, Interactions, Warnings". Archived from the original on 24 February 2024. Retrieved 1 December 2023.
  45. ^
    PMID 9165365
    .
  46. ^
    PMID 36891173
    .
  47. ISBN 978-0-7817-6879-5
    .
  48. PMID 25370135
    .
  49. ISBN 978-81-312-3259-0
    .
  50. ISBN 978-3-642-75561-3
    .
  51. ^
    PMID 35538735
    .
  52. PMID 31470575
    .
  53. PMID 8737746
    .
  54. PMID 23525348
    .
  55. ^
    PMID 12515585
    .
  56. ISBN 978-1-4614-9193-4
    .
  57. S2CID 45012360
    .
  58. PMID 11764306
    .
  59. doi:10.1016/j.ancr.2014.11.003
    .
  60. PMID 17357376
    .
  61. ISBN 978-0-323-04404-2. Archived
    from the original on 24 February 2024. Retrieved 14 February 2024.
  62. ^ "Center for drug evaluation and research. Application no. 21-066" (PDF). Archived (PDF) from the original on 14 February 2024. Retrieved 14 February 2024.
  63. PMID 1377628
    .
  64. PMID 34335590
    .
  65. S2CID 73482611
    .
  66. PMID 31463682
    .
  67. S2CID 236998913
    .
  68. S2CID 211246051
    .
  69. ^
    S2CID 24659435
    .
  70. ^
    S2CID 263801715
    .
  71. ^
    PMID 9759694
    .
  72. ISBN 978-0-323-37579-5. Archived
    from the original on 24 February 2024. Retrieved 14 February 2024.
  73. ISBN 978-3-527-60749-5. Archived
    from the original on 10 January 2023. Retrieved 1 August 2020.
  74. Drugbank. 12 April 2024. Archived
    from the original on 6 August 2019. Retrieved 16 November 2023.
  75. ^ "Ketotifen Fumarate". Inxight Drugs. Bethesda MD, US: National Center for Advancing Translational Sciences (NCATS). 12 April 2024. Archived from the original on 13 April 2024. Retrieved 13 April 2024.
  76. PMID 6806019. Archived
    from the original on 13 April 2024. Retrieved 13 April 2024.
  77. ^ "Drug Approval Package: Zaditor (Ketotifen Fumarate) NDA# 21-066". accessdata.fda.gov. 20 November 2001. Archived from the original on 8 March 2024. Retrieved 10 March 2024.
  78. ^ "Drug Approval Package: Acuvue Theravision with ketotifen". accessdata.fda.gov. 19 September 2022. Archived from the original on 10 March 2024. Retrieved 10 March 2024.
  79. ^ "Johnson & Johnson Vision Care Receives FDA Approval for Acuvue Theravision with Ketotifen – World's First and Only Drug-Eluting Contact Lens". Johnson and Johnson Vision (Press release). 2 March 2022. Archived from the original on 11 March 2024. Retrieved 10 March 2024.
  80. ^ "Ketotifen - Drug Usage Statistics". ClinCalc. Archived from the original on 4 June 2023. Retrieved 14 January 2024.
  81. ^ "Ketotifen International". Drugs.com. Archived from the original on 11 April 2021. Retrieved 4 September 2020.
  82. ^ Tata (28 March 2024). "What To Know About Ketotifen (popular Brands: Ketasma And Asthafen)". MSN. Archived from the original on 13 April 2024. Retrieved 2 April 2024.
  83. ^ "Ketotifen (Ingredient)". Archived from the original on 2 April 2024. Retrieved 2 April 2024.
  84. ^ "DailyMed - ZADITOR- ketotifen fumarate solution". National Institutes of Health. 15 December 2023. Archived from the original on 11 June 2021. Retrieved 5 September 2020.
  85. ^ "Trademark search - ZADITOR". USPTO. 8 April 2024. Archived from the original on 13 July 2021. Retrieved 8 April 2024.
  86. ^ Hanks v. Hubbard (C.D. Ill 8 March 2021).
  87. S2CID 237216445
    .
  88. ^ "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)". 25 January 2023. Archived from the original on 13 April 2024. Retrieved 13 April 2024.
  89. ^ "Efficacy and Safety of Norketotifen in Uncomplicated Influenza-like Illness: Influenza Clinical". 30 January 2023. Archived from the original on 13 April 2024. Retrieved 13 April 2024.
  90. ^ "Efficacy and Safety of Norketotifen in Uncomplicated Influenza-like Illness". 25 January 2023. Archived from the original on 20 April 2024. Retrieved 13 April 2024.
  91. ^ "Emergo finds midstage success in developing flu-fighter norketotifen + | Bioworld | BioWorld". Archived from the original on 13 April 2024. Retrieved 13 April 2024.
  92. ^ "Norketotifen in Influenza -Like Illness - Clinical Trials Registry - ICH GCP". Archived from the original on 13 April 2024. Retrieved 13 April 2024.
  93. ^
    PMID 24409414
    .
  94. ^
    S2CID 8888404. Archived
    from the original on 28 January 2024. Retrieved 10 January 2024.
  95. PMID 26755686
    .
  96. S2CID 18889707. Archived
    (PDF) from the original on 11 June 2021. Retrieved 24 September 2019.
  97. PMID 33810356
    .

External links

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