Ketotifen, an antihistamine and mast cell stabilizer used primarily to treat allergic conditions such as asthma and conjunctivitis, was developed in the 1970s and later approved for medical use in several countries. Its history is marked by its effectiveness in preventing allergic reactions rather than providing immediate relief. Ketotifen works by inhibiting the release of inflammatory mediators like histamine and leukotrienes. It is widely used in oral and ophthalmic forms, particularly for chronic management of allergic symptoms. Unlike some newer agents, its development did not involve major genetic screening concerns, but it has been associated with side effects such as sedation and weight gain. Over time, it has become a well-established option in allergy management and is often used as part of long-term preventive therapy.
BRAND NAMES
Ketasma
Asthafen
MECHANISM OF ACTION
Ketotifen acts primarily as a mast cell stabilizer and antihistamine. It inhibits the release of inflammatory mediators such as histamine, leukotrienes, and other cytokines from sensitized mast cells, thereby preventing allergic reactions. Additionally, it functions as a selective H1 histamine receptor antagonist, blocking the effects of histamine on target tissues like the respiratory tract and conjunctiva.
PHARMACOKINETICS
Absorption
Ketotifen is well absorbed after oral administration, with rapid uptake from the gastrointestinal tract. However, its absolute bioavailability is reduced to about 50% due to significant first-pass metabolism in the liver.
Distribution
Ketotifen has a relatively large volume of distribution (approximately 2.5–3.5 L/kg), indicating extensive distribution into body tissues. It is also highly bound to plasma proteins (about 75%), which facilitates its widespread penetration into various organs, including the lungs and other target tissues involved in allergic responses.
Metabolism
Ketotifen is extensively metabolized in the liver, primarily through processes such as glucuronidation and N-demethylation. The major metabolite formed is ketotifen-N-glucuronide, which is pharmacologically inactive.
Elimination
Ketotifen is eliminated primarily through the kidneys, with about 60–70% of the administered dose excreted in the urine, mainly as metabolites, and a small fraction excreted unchanged. The elimination occurs in a biphasic manner, with an initial short half-life followed by a longer terminal half-life of approximately 21 hours.
PHARMACODYNAMICS
Ketotifen exerts its pharmacological effects mainly through inhibition of mast cell degranulation and antagonism of histamine H1 receptors. By stabilizing mast cells, it prevents the release of inflammatory mediators such as histamine, leukotrienes, and platelet-activating factor that are responsible for allergic symptoms.
ADMINISTRATION
Ketotifen is usually administered orally in the form of tablets or syrup. It is typically taken twice daily, preferably with food to reduce gastrointestinal discomfort. The dosage depends on the patient’s age and clinical condition; in adults, the common dose is 1 mg twice daily, while in children dosing is adjusted according to body weight.
DOSAGE AND STRENGTH
Ketotifen is commonly available in oral tablet and syrup forms. The usual tablet strength for adults is 1 mg per tablet, administered twice daily (total 2 mg/day). For pediatric use, ketotifen is often provided as a syrup containing 1 mg/5 mL, with the dose adjusted according to age and body weight, typically ranging from 0.5 mg to 1 mg twice daily.
DRUG INTERACTIONS
Ketotifen may potentiate the effects of central nervous system depressants such as alcohol, sedatives, hypnotics, antihistamines, and opioid analgesics, leading to increased drowsiness and sedation. Concurrent use with other anticholinergic drugs may enhance anticholinergic side effects like dry mouth, blurred vision, and urinary retention.
FOOD INTERACTIONS
Ketotifen has minimal clinically significant food interactions. Alcohol should be avoided or used with caution during ketotifen therapy, as it can enhance central nervous system depression, leading to increased drowsiness and impaired alertness.
CONTRAINDICATIONS
Ketotifen is contraindicated in patients with known hypersensitivity to ketotifen or any component of the formulation. It should be used with caution in individuals with a history of epilepsy, as it may lower the seizure threshold in susceptible patients. It is also contraindicated or not recommended for use in acute asthma attacks because it does not provide immediate bronchodilation.
SIDE EFFECTS
Sedation / drowsiness (most common)
Fatigue or tiredness
Dizziness
Dry mouth
Increased appetite
Weight gain
OVER DOSE
Ketotifen overdose is characterized mainly by central nervous system depression or paradoxical CNS stimulation. Common symptoms include marked drowsiness, confusion, dizziness, hypotension, tachycardia, dry mouth, nausea, vomiting, and in severe cases, seizures or respiratory depression. In children, paradoxical symptoms such as agitation, irritability, and hyperactivity may occur.
TOXICITY
Ketotifen toxicity is generally related to excessive doses and is mainly due to its central nervous system and anticholinergic effects. Toxic manifestations include profound sedation, confusion, hypotension, tachycardia, respiratory depression, and, in severe cases, coma or seizures. Children may present with paradoxical excitation, irritability, or hyperactivity.
