Ketotifen is an antihistamine medication and a mast cell stabilizer used to treat allergic conditions such as conjunctivitis, asthma, and urticaria (hives).

This blocking 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 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 the ophthalmic form.

[5] Drug-eluting contact lenses, which release ketotifen medication, are used to help prevent itchy eyes caused by allergies.

[18] This blocking prevents the binding of histamine to these receptors and thus reduces the symptoms of histamine-mediated reactions, such as itching, sneezing, wheezing,[19][20] and swelling.

[17] Therefore, ketotifen, by blocking a calcium channel essential for mast cell activation,[22] helps reduce symptoms of allergic conditions.

[22] In Canada, Europe, and Mexico, oral ketotifen is commonly prescribed for these indications (asthma, hay fever, and conjunctivitis caused by mast cell activation).

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.

[26] The sedation side effect decreases over time during such long-term administration, but the antihistamine and mast cell stabilizing properties persist even if administered for 12 months or longer.

[33] Besides its anti-histaminic activity, it is also a functional leukotriene antagonist[34] (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)[35][36] and a phosphodiesterase inhibitor[37][38] (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).

[29] Side effects of systemic (oral) use include drowsiness, weight gain (5.0–5.4 kilograms (11.0–11.9 lb)), dry mouth, irritability, and increased nosebleeds.

In rare cases, systemic use of ketotifen may cause serious side effects such as anaphylaxis, liver dysfunction, blood disorders, or seizures.

[55][56][57] 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.

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.

[65] Ketotifen is a selective antihistamine – that is, an inverse agonist of the histamine H1 receptor (Ki = 0.166 nM)[66] – and mast cell stabilizer.

[67][68][69] 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.

[71] Ketotifen is a lipophilic compound that can cross the blood–brain barrier and exert central nervous system effects, such as sedation,[72] 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.

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.

[101][102][103] In the United States, ketotifen fumarate ophthalmic solution is marketed under brand name Zaditor, which is owned by Alcon Inc., a Swiss-American pharmaceutical company.

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.

In experiments, ketotifen inhibits mast cells from lung and tonsillar tissues when stimulated via an IgE-dependent histamine release mechanism.

In vitro studies using human liver microsomes and hepatocytes suggest that NK may be the major demethylated hepatic metabolite of ketotifen.

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.

[110][111][112][113][114] The underlying mechanisms of why ketotifen (similarly to other antihistamine drugs such as astemizole, azelastine)[90] may increase appetite and lead to weight gain in some people, are not fully understood.

[90] 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.

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.

[115] Studies on mice suggest that caffeine[115] or citrus aurantifolia oil[116] may prevent weight-gain induced by ketotifen, but, this has not been confirmed on human subjects.

[116] Ketotifen is being studied in context of a possible link between abnormalities in intestinal mast cells and irritable bowel syndrome, but there are no solid results yet.