What is Ketotifen?
Ketotifen is a dual-action medication that functions as both an H1-antihistamine and a mast cell stabilizer, primarily used for treating allergic conjunctivitis and available over-the-counter as a 0.035% ophthalmic solution for patients 3 years and older. 1
Mechanism of Action
Ketotifen works through multiple complementary mechanisms:
- Blocks histamine H1 receptors to prevent histamine-mediated allergic symptoms 2
- Stabilizes mast cell membranes to prevent degranulation and release of inflammatory mediators, with demonstrated 90% or more inhibition of histamine and tryptase release from human conjunctival mast cells at clinically relevant concentrations 3
- Inhibits eosinophil activity by decreasing chemotaxis and activation of eosinophils 2, 4
This triple mechanism distinguishes ketotifen from simple antihistamines (cromones), providing both immediate symptom relief and prophylactic protection 5
Clinical Indications
Primary Use: Allergic Conjunctivitis
Ketotifen is recommended by the American Academy of Allergy, Asthma, and Immunology as a first-line dual-action agent for allergic conjunctivitis due to its rapid onset and ability to treat acute symptoms while preventing future episodes 6, 7
- Provides rapid onset of action within 15 minutes of administration 2
- Maintains efficacy for at least 8 hours, supporting twice-daily dosing 2
- Suitable for both acute symptom relief and longer-term prophylactic treatment 7
Additional Indications
Ketotifen is also indicated for:
- Prophylactic treatment of allergic asthma (particularly in children and young adults with intermittent or mildly persistent asthma) 5
- Allergic rhinitis 5
- Manifestations of food allergy 5
Formulation and Availability
- Available as 0.035% ophthalmic solution (previously 0.025% in prescription formulations) 1, 2
- Now available over-the-counter without prescription for ages 3 years and older 1
- Marketed as "original prescription strength" for eye itch relief 1
- Can be stored in the refrigerator for additional cooling relief upon instillation 6
Clinical Efficacy
In controlled trials using the conjunctival allergen challenge model:
- Significantly superior to placebo in reducing ocular itching at all post-challenge time points (3,7, and 10 minutes) when administered 15 minutes, 6 hours, and 8 hours before allergen exposure (P<0.001) 2
- Significantly reduced ocular hyperemia compared to placebo at all time points (P<0.05) 2
- Comparable efficacy to olopatadine 0.1% in reducing clinical scores and expression of cell adhesion molecules and inflammatory markers in conjunctival surface cells 8
Safety Profile
Ketotifen demonstrates excellent tolerability:
- Incidence of ocular adverse events was 18.2% in a 6-week study, compared with 15.2% with placebo 4
- No ocular rebound vasodilation or itching observed within 48 hours after treatment discontinuation 4
- Preserves cell viability at all clinically relevant concentrations that stabilize mast cells 3
- Secondary effects are rare and generally benign, with reduced contraindications 5
- Safe and well tolerated in both adult and pediatric populations 4
Clinical Positioning
The American Academy of Allergy, Asthma, and Immunology positions ketotifen alongside olopatadine, epinastine, and azelastine as preferred first-line dual-action agents for allergic conjunctivitis, superior to mast cell stabilizers alone (which require several days for optimal effect) and safer than topical corticosteroids (which carry risks of elevated intraocular pressure and cataract formation) 6, 7
Unlike oral antihistamines, which may worsen dry eye syndrome and impair the tear film's protective barrier, topical ketotifen provides targeted ocular relief without systemic side effects 6