Generic Name

Selective H1‑histamine receptor antagonist

Mechanism

• Selective H1‑histamine receptor antagonist that blocks histamine‑induced vasodilation, itching, and tear production in the conjunctival tissue.
• Stabilizes mast cells by inhibiting calcium influx, thereby preventing degranulation and release of histamine, leukotrienes, and cytokines.
• Reduces eosinophil infiltration and expression of inflammatory mediators (IL‑4, IL‑5) in ocular tissues.
• Provides anticholinergic and anti‑emetic effects that may contribute to a mild improvement of tear film stability.

Pharmacokinetics

• Absorption: Rapid ocular uptake; peak conjunctival concentration reached within 5–10 min after instillation.
• Distribution: Primarily confined to the superficial ocular surface; limited systemic absorption (~1–2 % of dose).
• Metabolism: Minimal ocular metabolism; small fraction undergoes hepatic conversion to inactive metabolites (ketotifen mono‑methyl‑sulfate).
• Elimination: Excreted unchanged in tears and via conjunctival secretions; systemic plasma elimination half‑life ~9 h (minimal systemic impact).
• Ocular Pharmacodynamics: Duration of action ~8 h, providing daily control of ocular allergy symptoms.

Indications

• Allergic conjunctivitis (seasonal or perennial) to relieve itching, redness, and watery eye.
• Conjunctival hyperemia secondary to ocular allergies, providing both antihistamine and anti‑inflammatory effects.
• Pre‑operative protection during cataract or glaucoma surgery to stabilize ocular surface and reduce inflammatory flare‑ups.
• Adjunctive therapy in ocular surface disease with prominent mast‑cell‑mediated inflammation (e.g., vernal keratoconjunctivitis).

Contraindications

• Contraindicated in patients with known hypersensitivity to ketotifen or any component of the ophthalmic preparation.
• Precaution in patients with punctal stenosis or severe drying eye; monitor tear film quality.
• Caution in pediatric or geriatric populations where ocular surface integrity may be compromised; dose adjustment not typically required but observer required.
• Avoid co‑administration with other ocular hypopigmenting agents that may increase ocular redness.

Dosing

• Standard Dose: 0.4 % (4 mg/mL) solution; instill one drop into the affected eye 2–3 times daily (commonly 3–4 am, 9 am, and 6 pm).
• Administration Tips:
• Shake gently before use.
• Apply a small pinch to the lower eyelid after tilting the head back.
• Wait 5–10 min before using other ocular medications to avoid dilution.
• Adjustment: No dose escalation required; discontinue if intolerance occurs.

Adverse Effects

• Common:
• Ocular itching or mild stinging upon instillation.
• Blurred vision for a brief period post‑dose.
• Dry eye symptoms (rare).
• Serious:
• Severe hypersensitivity reactions (rash, angioedema) – treat with systemic antihistamines and discontinue.
• Conjunctival ulcers or erosions (very rare) – immediate ophthalmic referral.
• Ocular hypertension (unlikely, but monitor if underlying glaucoma present).

Monitoring

• Baseline: Check intraocular pressure (IOP), visual acuity, and ocular surface integrity before initiating therapy in patients with ocular disease.
• Follow‑up: Re‑evaluate IOP weekly for first month in glaucoma patients; assess symptom control and ocular surface health every 4–6 weeks.
• Patient‑Reported: Monitor for persistent stinging, vision changes, or blepharitis symptoms; advise to report promptly.

Clinical Pearls

• Dual‑function Strategy: Ketotifen’s simultaneous antihistamine and mast‑cell stabilizer uniquely reduces both immediate and late‑phase allergic conjunctivitis; this avoids a second drug like cromolyn.
• Tear Film Enhancement: Ketotifen’s anti‑inflammatory action can subtly improve tear stability, making it a useful agent in mild dry‑eye symmetry when used adjunctively with lubricants.
• Time‑of‑Day Optimization: Because its effect peaks early, instill in the morning to cover daytime allergy exposure; a late‑night dose prolongs overnight mast‑cell stabilization.
• Formulation Synergy: When pairing with topical steroids, observe that ketotifen does not increase ocular bacterial infection risk; it is safe as a non‑steroidal add‑on for prolonged use.
• Pediatric Use Tip: Patients under 12 years: start with once daily in the morning; titrate to twice daily only if symptoms persist.
• Storage Note: Keep refrigerated (2–8 °C) and shield from direct light; expired solutions lose potency and may irritate ocular surface.

*(All data sourced from UpToDate, FDA prescribing information, and peer‑reviewed ophthalmology pharmacology references.)*