Ketotifen

Ketotifen fumarate is a benzocycloheptathiophene H1 antihistamine with mast cell-stabilizing activity, classed with sedating antihistamines. In the US it is FDA approved only as an ophthalmic solution (Zaditor and Alaway, nonprescription). There is no FDA-approved oral ketotifen product in the US; oral products are approved in other countries. Lake Hills Pharmacy compounds oral ketotifen capsules as a 503A pharmacy on patient-specific prescriptions.

Ophthalmic ketotifen is FDA labeled for temporary relief of itchy eyes due to allergic conjunctivitis (pollen, ragweed, grass, animal hair and dander). Prescribers use compounded oral ketotifen for allergic conditions and mast cell-related disorders. No FDA-labeled indication or dose exists for oral ketotifen in the US.

Ketotifen is a noncompetitive H1 receptor antagonist. It also stabilizes mast cells, reducing release of histamine, leukotrienes and other mediators, and inhibits eosinophil activation and accumulation. Its mast cell effects develop over weeks of regular use.

Oral ketotifen is well absorbed, but first-pass metabolism gives a bioavailability of about 50%. Peak plasma levels occur in 2 to 4 hours. It is about 75% protein bound. Elimination is biphasic, with a short initial half-life of a few hours and a terminal half-life of about 21 hours. It is metabolized to an inactive N-glucuronide and to norketotifen, and excreted mainly in urine as metabolites.

• Hypersensitivity to ketotifen or any component of the preparation.

• Sedation and impaired alertness, most marked at the start of therapy; caution with driving and machine operation.
• Seizures have been reported; use caution in patients with a history of epilepsy.
• Ketotifen is not a bronchodilator or rescue therapy and does not treat acute asthma or anaphylaxis. Do not stop existing asthma or anaphylaxis therapy when it is started.
• Use caution in hepatic impairment and in young children, in whom excitation and irritability are more common.

• CNS depressants (alcohol, sedatives, hypnotics, opioids, other antihistamines): additive sedation.
• Oral antidiabetic agents: reversible thrombocytopenia has been reported with concomitant oral ketotifen; monitor platelet counts.
• Anticholinergic drugs: possible additive anticholinergic effects.

Oral: drowsiness, dizziness, dry mouth, increased appetite and weight gain, irritability, nervousness and insomnia (especially in children), headache and nausea. Rare: seizures, hepatitis and elevated liver enzymes, thrombocytopenia, and severe skin reactions. Ophthalmic: conjunctival injection, burning, headache and rhinitis.

Animal studies did not show teratogenicity, but human pregnancy data are limited. Ketotifen passes into animal milk and is presumed to pass into human milk. Use of oral ketotifen in pregnancy or breastfeeding is a prescriber decision.

Sedation and tolerability, weight, symptom control at intervals set by the prescriber, and platelet counts in patients also taking oral antidiabetic agents.

• Zaditor (ketotifen fumarate ophthalmic solution) Drug Facts label, Alcon.
• Martindale: The Complete Drug Reference, Pharmaceutical Press.
• Lexicomp Drug Information, Wolters Kluwer.