ORCHAZID OPHTHALMIC SOLUTION

Indications

• Allergic rhinitis
• Asthma
• Allergic conjunctivitis

Dosage

Children: For children aged 7 years and older, 1 mg twice daily.

Adults: Initially, 1 mg once daily, may increase to 2 mg if necessary.

Mechanism of action

Ketotifen exerts its therapeutic effects primarily through its function as a non-competitive antagonist of H1 histamine receptors. It stabilizes mast cells and inhibits the release of allergic mediators such as histamine, leukotrienes, and platelet-activating factor. This mechanism contributes to its anti-allergic and antiasthmatic properties, helping to manage airway hyperreactivity and prevent bronchoconstriction.

Pharmacodynamics

Ketotifen acts as a non-competitive histamine antagonist and mast cell stabilizer. It does not function as a bronchodilator but provides antiasthmatic effects by inhibiting inflammatory mediators. Its antihistamine effects are distinct from its antiallergic properties, and while some effects may take 6 to 12 weeks to become apparent, ketotifen has been shown to reduce asthma symptoms and may decrease the need for other asthma medications.

Pharmacokinetics

Ketotifen is well absorbed when administered orally and is extensively metabolized in the liver. The drug has a half-life that supports once or twice daily dosing. Its bioavailability may be affected by food intake, and it is excreted primarily via urine. Side effects, such as drowsiness, are common due to its central nervous system activity.

Contra-indications

• QT interval prolongation
• significant electrolyte imbalance
• bradycardia
• cardiovascular disease
• family history of sudden cardiac death
• bladder outflow obstruction
• severe cutaneous adverse reactions
• angle-closure glaucoma
• urinary retention

Adverse effects

• drowsiness
• dry mouth
• dizziness
• fatigue
• anxiety
• insomnia
• irritability
• nausea
• vomiting
• palpitations
• seizures (with high doses)
• sexual dysfunction
• skin reactions
• thrombocytopenia
• hepatitis
• tinnitus
• weight increase
• urinary disorders
• vision disorders
• sleep disorders
• slurred speech
• bitter taste
• cystitis
• vertigo

Interactions

• Caution with sedating antihistamines
• other CNS depressants may enhance sedation
• alcohol may increase CNS effects
• use with caution in patients taking medications that prolong QT interval

Precautions

• Elderly patients may be more susceptible to side effects
• children may have increased susceptibility to CNS effects
• use with caution in patients with a history of epilepsy
• caution in patients with hyperthyroidism, myasthenia gravis, or prostatic hypertrophy

Pregnancy

Manufacturers generally advise avoiding use during pregnancy; however, specific data on toxicity is limited.

Breast-feeding

Caution is advised as ketotifen may be excreted in breast milk; consult a healthcare professional.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Oral suspension
• Oral solution
• Tablets (10 mg, 25 mg)

Mechanism of action

The precise mechanism(s) through which ketotifen exerts its therapeutic effects are unclear. Ketotifen is a potent and non-competitive antagonist of H1 histamine receptors, which is likely to be a significant contributor to its anti-allergic activity. In addition, ketotifen stabilizes mast cells and has demonstrated _in vitro_ the ability to inhibit the release of allergic and inflammatory mediators such as histamine, leukotrienes C₄ and D₄ (i.e. SRS-A), and platelet-activating factor (PAF). Other _in vivo_ observations thought to contribute to ketotifen's efficacy in asthma include the inhibition of various PAF-mediated processes (e.g. airway hyperreactivity, eosinophil and platelet accumulation in the airways), prevention of leukotriene-induced bronchoconstriction, and suppression of eosinophil priming. Ketotifen is a non-bronchodilator antiasthmatic drug which inhibits the effects of certain endogenous substances known to be inflammatory mediators, and thereby exerts antiallergic activity. Ketotifen possesses a powerful and sustained non-competitive histamine (H1) blocking property. Ketotifen's antihistamine (H1) effect seems to be distinct from it antiallergic properties. Properties of ketotifen which may contribute to its antiallergic activity and its ability to affect the underlying pathology of asthma include: In Vivo results: Inhibition of the development of airway hyperreactivity associated with activation of platelets by PAF (Platelet Activating Factor) or caused by neural activation following the use of sympathomimetic drugs or the exposure to allergen; inhibition of PAF-induced accumulation of eosinophils and platelets in the airways; suppression of the priming of eosinophils by human recombinant cytokines and thereby suppression of the influx of eosinophils into inflammatory loci; antagonism of bronchoconstriction due to leukotrienes. In Vitro results: inhibition of the release of allergic mediators such as histamine, leukotrienes C4 and D4 (SRS-A) and PAF. /Ketotifen fumarate (systemic)/

Pharmacodynamics

Ketotifen is a non-competitive histamine antagonist and mast cell stabilizer. Administered orally, it functions as a non-bronchodilator antiasthmatic drug by inhibiting the effects of endogenous substances known to be inflammatory mediators. While effects can take 6 to 12 weeks to become apparent, the use of ketotifen has been demonstrated to reduce the frequency, severity, and duration of asthma symptoms, and may allow for a reduction in the use of other asthma therapies.