Ketotifen is an antihistamine medication and a mast cell stabilizer used to treat allergic conditions such as conjunctivitis (pink eye), asthma, and 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 conditions such as asthma attacks and allergic reactions. In addition to treating allergies, ketotifen has shown efficacy in managing systemic mast cell diseases such as mastocytosis and mast cell activation syndrome (MCAS), which involve abnormal accumulation or activation of mast cells throughout the body. Ketotifen is also used for other allergic-type conditions like atopic dermatitis (eczema) and food allergies.
Ketotifen acts by blocking the H1 histamine receptors, which are found on various cells in the body, such as smooth muscle, endothelium, and nerve cells. 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 also prevents the release of histamine and other inflammatory substances from immune cells (mast cells); this action helps reduce symptoms of conditions (including allergic conditions) by blocking the activation of these cells. In addition to its antihistaminic activity, ketotifen is also a leukotriene antagonist, which blocks inflammation-causing chemicals known as leukotrienes; it also acts as a phosphodiesterase inhibitor that regulates blood vessel dilation.
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. 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.
In 2023, it was the 299th most commonly prescribed medication in the United States, with more than 400,000 prescriptions.
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: in its ophthalmic form (eye drops or drug-eluting contact lenses), it is used to treat allergic conjunctivitis; in its oral form (tablets or syrup), it is used to prevent asthma attacks or anaphylaxis, as well as various mast cell and allergy 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. The safety and effectiveness of ketotifen eye drops in children under three years of age have not been established, whereas drug-eluting contact lenses have not been studied in children under eleven years of age.
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, namely, 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.
Oral ketotifen is used to treat asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, chronic urticaria (hives), cold-induced urticaria, cholinergic urticaria, and exercise-induced urticaria. It is also used for systemic mast cell diseases such as mastocytosis and mast cell activation syndrome (MCAS), as well as allergic and nonallergic anaphylaxis.
As an antihistamine medication, ketotifen acts by blocking the H1 histamine receptors, which are found on various cells in the body, such as smooth muscle, endothelium, and nerve cells. 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.
As a mast cell stabilizer to treat MCAS, oral ketotifen prevents the release of histamine and other inflammatory substances from mast cells, which are immune cells that react to allergens. Therefore, ketotifen, by blocking a calcium channel essential for mast cell activation, helps reduce symptoms of conditions typically associated with mast cell activation. These conditions include asthma, hay fever, and conjunctivitis. Calcium channels are proteins in mast cell membranes that allow calcium ions to enter the cell, triggering the release of histamine and other inflammatory substances. When these channels open, calcium floods into the cells, causing them to degranulate. Ketotifen inhibits calcium influx into cells, reducing mast cell degranulation. In Canada, Europe, and Mexico, oral ketotifen is commonly prescribed for these indications (asthma, hay fever, and conjunctivitis caused by mast cell activation). In patients with MCAS, ketotifen reduces episodes of flushing, gastrointestinal symptoms (such as abdominal pain, diarrhea), respiratory symptoms (such as wheezing), and other systemic manifestations. Treatment plans for MCAS typically involve a combination of medications targeting different aspects of mast cell activation along with lifestyle modifications to minimize triggers.
The maximum antihistamine and mast cell stabilizing effect of oral ketotifen is achieved on long-term administration, and a period of at least 6-12 weeks is necessary for a maximum therapeutic effect to start. 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.
In the United States, the Food and Drug Administration (FDA) has not approved an oral formulation of ketotifen; however, oral ketotifen is available through compounding pharmacies with a prescription. Ketotifen eye drops are approved in the US for people who are at least three years of age. In the EU, oral ketotifen (syrup, tablets, and capsules) is authorized for adult use at the national level by individual member states. In the UK, ketotifen is available as tablets and elixir (liquid).
Oral ketotifen can be used as a long-term control medication for asthma and wheeze in children. The drug has been shown to improve asthma control by reducing the need for bronchodilators, decreasing symptoms, preventing exacerbations, and reducing the use of rescue oral steroids. Ketotifen is effective when used alone or in combination with other medications and is an alternative to inhaled therapy for asthma in children, especially for younger children who may have difficulty using inhalers.
One small study in men found that the mean elimination half-life of oral 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).
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, whereas drug-eluting contact lenses are not recommended for children under eleven years of age.
For oral ketotifen, the contraindication is for known hypersensitivity to any component of the product. Caution should be taken on the following conditions: acute porphyrias (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). Unlike other histamines, ketotifen appears to be relatively safe in acute porphyria, still, caution should be taken. epilepsy (a disorder causing recurrent seizures) - ketotifen may increase the risk of seizures, pyloroduodenal obstruction (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, which connects the eye to the brain), and urinary retention (inability to urinate).
The use of ketotifen eye drops during pregnancy and lactation is considered safe, as absorption through the eye is limited. The eye drops are 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. 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.
Side effects Common side effects of ophthalmic use are eye redness and 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.
Side effects of systemic (oral) use include drowsiness, weight gain (), dry mouth, irritability, and increased nosebleeds. 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.
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.
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.
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.