Olopatadine - Drug Monograph

Introduction

Olopatadine is a second-generation selective histamine H1-receptor antagonist and mast cell stabilizer used primarily in ophthalmology for the treatment of allergic conjunctivitis. It belongs to the drug class of ocular antihistamines and is available as both prescription and over-the-counter formulations in various countries.

Mechanism of Action

Olopatadine exerts its therapeutic effects through dual mechanisms: 1. Histamine H1-receptor antagonism: Competitively inhibits histamine binding at H1 receptors, preventing the allergic response in conjunctival tissue 2. Mast cell stabilization: Inhibits the release of histamine and other inflammatory mediators (including tryptase, prostaglandin D2, and leukotrienes) from mast cells

Additionally, olopatadine demonstrates anti-inflammatory properties by inhibiting cytokine production and eosinophil chemotaxis, providing comprehensive control of ocular allergic responses.

Indications

• FDA-approved:

- Treatment of ocular itching associated with allergic conjunctivitis - Prevention of ocular itching in allergic conjunctivitis

• Off-label uses:

- Vernal keratoconjunctivitis - Giant papillary conjunctivitis - Allergic rhinoconjunctivitis (when combined with nasal formulation)

Dosage and Administration

• Adults and children ≥3 years: One drop in affected eye(s) twice daily, approximately 6-8 hours apart
• Administration: Tilt head back, pull down lower eyelid, instill drop into conjunctival sac
• Contact lens wearers: Remove lenses before instillation; may reinsert after 10 minutes

• Geriatric: No dosage adjustment required
• Renal/hepatic impairment: No specific recommendations; systemic absorption is minimal
• Pediatric: Safety and efficacy established for children ≥3 years

Pharmacokinetics

• Absorption: Minimal systemic absorption following ocular administration (<0.01 ng/mL plasma concentrations)
• Distribution: Primarily localized to ocular tissues; negligible systemic distribution
• Metabolism: Minimal hepatic metabolism; not significantly metabolized by cytochrome P450 enzymes
• Elimination: Primarily eliminated unchanged in urine; half-life approximately 3 hours
• Protein binding: Approximately 55% bound to human plasma proteins

Contraindications

• Hypersensitivity to olopatadine hydrochloride or any component of the formulation
• History of anaphylactoid reactions to olopatadine

Warnings and Precautions

• Ocular effects: May cause transient burning, stinging, or blurred vision immediately after instillation
• Contact lens use: Preservative (benzalkonium chloride) may be absorbed by soft contact lenses
• Superinfection: Prolonged use may result in ocular fungal or bacterial infections
• Corneal effects: Use with caution in patients with corneal abrasions or epithelial defects
• Pregnancy: Category C - Use only if potential benefit justifies potential risk to fetus
• Lactation: Exercise caution; unknown if excreted in human milk

Drug Interactions

• Minimal systemic interactions due to low systemic absorption
• Theoretical interactions: May potentiate effects of CNS depressants (though unlikely due to minimal absorption)
• No clinically significant interactions with systemically administered drugs reported

Adverse Effects

• Headache (7%)
• Burning/stinging upon instillation (∼5%)
• Dry eye (∼3%)
• Foreign body sensation (∼3%)
• blurred vision (∼3%)

• Ocular irritation/discomfort
• Hyperemia
• Corneal staining
• Photophobia
• Allergic reactions (eyelid edema, rash)
• Unpleasant taste (if nasolacrimal drainage occurs)

• Keratitis
• Dizziness
• Fatigue
• Nasopharyngitis

Monitoring Parameters

• Efficacy: Reduction in ocular itching, redness, and allergic symptoms
• Safety: Ocular examination for signs of irritation or infection with prolonged use
• Patient adherence: Regular assessment of administration technique and compliance
• Therapeutic response: Subjective improvement in allergy symptoms

Patient Education

• Administration technique: Wash hands before use; avoid touching dropper tip to any surface
• Timing: Use approximately 6-8 hours apart for optimal effect
• Contact lenses: Remove before instillation; wait at least 10 minutes before reinserting
• Storage: Store at room temperature; protect from light
• Multiple medications: Wait at least 5 minutes between different eye drops
• Duration: Use regularly during allergy season for optimal prevention
• Side effects: Report persistent irritation, pain, or vision changes to healthcare provider
• Discard: Do not use beyond expiration date; discard bottle 28 days after opening

References

1. Sharif NA, Xu SX, Yanni JM. Olopatadine (AL-4943A): ligand binding and functional studies on a novel, long acting H1-selective histamine antagonist and anti-allergic agent. J Pharm Pharmacol. 1996;48(3):297-303.

2. Abelson MB, Chapin MJ. Evaluation of the new ophthalmic antihistamine, olopatadine hydrochloride, in the conjunctival allergen challenge model. Ann Allergy Asthma Immunol. 1999;83(6):529-536.

3. Greiner JV, Minno G. A placebo-controlled comparison of olopatadine and ketotifen for treating allergic conjunctivitis. Adv Ther. 2001;18(4):165-171.

4. FDA Prescribing Information: Patanol® (olopatadine hydrochloride ophthalmic solution) 0.1%. Revised 2011.

5. Bielory L, Katelaris CH, Lightman S, et al. Treating the ocular component of allergic rhinoconjunctivitis and related conditions. Allergy Asthma Proc. 2017;38(3):149-160.

6. Ono SJ, Lane K. Comparison of the effects of olopatadine and ketotifen on conjunctival epithelial cells. J Allergy Clin Immunol. 1999;103(5 Pt 2):S146-S151.

7. McGill JI, Holgate ST, Church MK, et al. Allergic eye disease mechanisms. Br J Ophthalmol. 1998;82(10):1203-1214.