Introduction
Zaditor (ketotifen fumarate) is a second-generation antihistamine and mast cell stabilizer ophthalmic solution used primarily for the prevention and treatment of ocular itching associated with allergic conjunctivitis. Available as an over-the-counter medication in many countries, it provides dual-action relief by addressing both immediate and delayed allergic responses.
Mechanism of Action
Zaditor exerts its therapeutic effects through multiple mechanisms:
- Mast cell stabilization: Inhibits the release of histamine and other mediators (leukotrienes, cytokines) from mast cells
- Histamine H1-receptor antagonism: Competitively blocks histamine binding to H1-receptors
- Eosinophil inhibition: Reduces eosinophil chemotaxis and activation
- Anti-inflammatory effects: Modulates inflammatory pathways beyond histamine blockade
Indications
- Prevention and treatment of ocular itching associated with allergic conjunctivitis
- Temporary relief of itchy eyes due to pollen, ragweed, grass, animal hair, or dander
Dosage and Administration
Standard dosing: One drop in affected eye(s) every 8-12 hours Administration:- Wash hands before use
- Avoid touching dropper tip to any surface
- Tilt head back, pull down lower eyelid
- Apply drop to conjunctival sac
- Close eyes gently for 1-2 minutes
- Do not rinse dropper
- Wait 10 minutes before inserting contact lenses
- Pediatric use: Safety established for children ≥3 years
- Geriatric use: No dosage adjustment required
- Renal/hepatic impairment: No specific recommendations (minimal systemic absorption)
Pharmacokinetics
Absorption: Minimal systemic absorption following ocular administration (<5 ng/mL detectable in plasma) Distribution: Primarily local ocular tissue distribution Metabolism: Hepatic metabolism via cytochrome P450 system to inactive metabolites Elimination: Primarily renal excretion (approximately 60-70% of systemically absorbed drug) Half-life: Approximately 12 hours (systemic)Contraindications
- Hypersensitivity to ketotifen fumarate or any component of the formulation
- Active ocular infections (bacterial, viral, or fungal)
Warnings and Precautions
- Contact lens wearers: Remove lenses before administration; may reinsert after 10 minutes
- Ocular effects: May cause transient stinging, burning, or blurred vision
- Superinfection: Prolonged use may result in ocular fungal or bacterial infections
- Systemic effects: Although rare, systemic antihistamine effects possible (drowsiness, dry mouth)
- Pregnancy: Category C - Use only if potential benefit justifies potential risk
- Lactation: Exercise caution; unknown if excreted in human milk
Drug Interactions
- CNS depressants: Potential additive sedative effects (alcohol, benzodiazepines, opioids)
- Other anticholinergics: Possible enhanced anticholinergic effects
- MAO inhibitors: Theoretical potential for enhanced antihistamine effects
- Topical ocular medications: Allow 5-10 minutes between administration of different eye drops
Adverse Effects
Common (≥1%-10%):- Transient burning/stinging upon instillation (25%)
- Conjunctival injection (10%)
- Headache (5%)
- Rhinitis (3%)
- Dry eyes (2%)
- Corneal erosion
- Photophobia
- Ocular discharge
- Eyelid edema
- Drowsiness (systemic effect)
- Taste perversion
- Hypersensitivity reactions
- Stevens-Johnson syndrome (case reports)
- Keratitis
Monitoring Parameters
- Efficacy: Reduction in ocular itching symptoms
- Safety: Ocular examination for signs of irritation or infection
- Patient adherence: Proper administration technique
- Long-term use: Periodic assessment for superinfection
- Systemic effects: Monitoring for drowsiness in sensitive populations
Patient Education
- Use exactly as directed; do not exceed recommended dosage
- Temporary stinging or burning upon application is normal
- Wait at least 10 minutes before inserting contact lenses
- Do not use if solution changes color or becomes cloudy
- Discard bottle 28 days after opening
- Avoid touching dropper tip to prevent contamination
- Report persistent irritation, pain, or vision changes to healthcare provider
- May cause drowsiness in sensitive individuals; use caution when driving or operating machinery
- Store at room temperature (15-25°C); protect from light
References
1. FDA Label: Zaditor (ketotifen fumarate) Ophthalmic Solution [Internet]. DailyMed. 2021. 2. Abelson MB, Welch DL. An evaluation of onset and duration of action of patanol (olopatadine hydrochloride ophthalmic solution 0.1%) compared to zaditor (ketotifen fumarate ophthalmic solution 0.025%) in the acute conjunctival allergen challenge model. Clin Ther. 2000;22(7):826-833. 3. Greiner JV, Udell IJ. A comparison of the efficacy and tolerability of olopatadine hydrochloride 0.1% ophthalmic solution and ketotifen fumarate 0.025% ophthalmic solution in the conjunctival allergen challenge model. Clin Ther. 2001;23(8):1272-1280. 4. Sharif NA, Xu SX, Miller ST, et al. Characterization of the ocular antiallergic and antihistaminic effects of olopatadine (AL-4943A), a novel drug for treating ocular allergic diseases. J Pharmacol Exp Ther. 1996;278(3):1252-1261. 5. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. Ketotifen. [updated 2023]. 6. Micromedex Solutions [Internet]. Truven Health Analytics. Ketotifen Ophthalmic. [updated 2023].