Ketotifen

Antihistamine medication

in its oral form (tablets or syrup), as well as various mast cell, allergic type disorders. 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,

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. In the UK, ketotifen is available as tables and elixir (liquid). 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. The mean elimination half life of ketotifen is 12 hours. Besides its anti histaminic activity, it is also a functional leukotriene antagonist (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) and a phosphodiesterase inhibitor (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).

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, whereas drug eluting contact lenses are not recommended for children under eleven years of age. 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. 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 alcohol, antihistamines, opioids, benzodiazepines, or antidepressants. Systemic use of ketotifen may affect the results of some laboratory tests, such as skin tests for allergies or blood glucose levels.

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. The most common symptom of ketotifen overdose is significant sedation. Other symptoms may include confusion, disorientation, agitation, hallucinations, 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. Oral ketotifen may interact with amphetamine and benzphetamine, which may decrease the activities of ketotifen. The concomitant use of oral ketotifen with amifampridine, bupropion, donepezil, and pitolisant, is not recommended. 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.

Ketotifen is a noncompetitive H1 antihistamine and mast cell stabilizer. There is no academic consensus on whether ketotifen should be classified as a medication belonging to the first or the second generations of antihistamine drugs; the classification can vary depending on the criteria used and the context of the study, 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. While ketotifen has some sedative properties, it is generally considered to have a milder sedative effect compared to traditional first generation antihistamines,

Ketotifen was patented in 1970 and came into medical use in 1976. Ketotifen was developed and patented by Sandoz Pharmaceuticals (currently a part of Novartis), a Swiss company. Ketotifen was approved for medical use in Canada in December 1990. The contact lens with ketotifen was approved for medical use in the United States in 2022.

In 2021, it was the 301st most commonly prescribed medication in the United States, with more than 400000 prescriptions.

Ketotifen is sold under various brand names worldwide, depending on country and formulation, with over 200 different names used. 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.

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.

Research directions for ketotifen include the investigation of norketotifen (NK), a metabolite of ketotifen. In vitro studies using human liver microsomes and hepatocytes suggest that NK may be the major 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. The potential future applications of norketotifen are researched by Emergo Therapeutics, a US company.

The underlying mechanisms of why ketotifen (similarly to other antihistamine drugs such as astemizole, azelastine) Studies on mice suggest that caffeine may prevent weight gain induced by ketotifen, but, this has not been confirmed on human subjects.

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.