Brimonidine - Drug Monograph

Introduction

Brimonidine is a selective alpha-2 adrenergic receptor agonist primarily used in ophthalmology for the management of open-angle glaucoma and ocular hypertension. First approved by the FDA in 1996, it has become a well-established therapeutic agent in glaucoma management. Brimonidine is also used in dermatology for the treatment of persistent facial erythema associated with rosacea.

Mechanism of Action

Brimonidine exerts its therapeutic effects through several mechanisms:

• Alpha-2 adrenergic agonism: Reduces aqueous humor production via vasoconstriction of afferent ciliary process blood vessels
• Increases uveoscleral outflow: Enhances drainage of aqueous humor through alternative pathways
• Neuroprotective effects: May protect retinal ganglion cells through modulation of glutamate excitotoxicity and apoptosis pathways

The drug's dual mechanism of action (reducing production and enhancing outflow) makes it particularly effective for intraocular pressure reduction.

Indications

• Reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension
• Topical treatment of persistent facial erythema of rosacea in adults

• Prophylaxis and treatment of ocular allergic reactions
• Management of ocular surface diseases
• Adjunctive therapy in various glaucoma types

Dosage and Administration

• Standard dose: One drop in affected eye(s) three times daily approximately 8 hours apart
• Some formulations allow for twice-daily dosing (0.15% and 0.2% solutions)

• Rosacea treatment: Apply a pea-sized amount to entire face once daily

• Pediatric patients: Safety and effectiveness not established for glaucoma treatment under age 2
• Geriatric patients: No dosage adjustment required
• Renal/hepatic impairment: Use with caution; limited data available

Pharmacokinetics

• Ophthalmic: Limited systemic absorption following conjunctival instillation
• Topical: Minimal systemic absorption when applied to facial skin

• Protein binding: Approximately 30%
• Volume of distribution: Approximately 1.6 L/kg

• Primarily hepatic metabolism via cytochrome P450 enzymes
• Extensive first-pass metabolism

• Elimination half-life: Approximately 3 hours
• Primarily renal excretion (74% of dose)
• Biliary excretion accounts for remainder

Contraindications

• Hypersensitivity to brimonidine or any component of the formulation
• Patients receiving monoamine oxidase (MAO) inhibitor therapy
• Neonates and infants (ophthalmic use)
• Severe cardiovascular disease (relative contraindication)

Warnings and Precautions

• May cause hypotension, bradycardia, and syncope
• Use with caution in patients with cardiovascular disease

• Drowsiness and fatigue reported in 10-30% of patients
• Potential for impaired mental alertness affecting driving or operating machinery

• Allergic reactions including conjunctival hyperemia, itching, and follicular conjunctivitis
• Mydriasis may occur, potentially precipitating angle-closure glaucoma in susceptible patients

• Pregnancy Category B: Use only if clearly needed
• Nursing mothers: Exercise caution; unknown if excreted in human milk

Drug Interactions

• MAO inhibitors: Contraindicated due to risk of hypertensive crisis
• Antihypertensives: Additive hypotensive effects
• CNS depressants: Enhanced sedative effects (alcohol, benzodiazepines, opioids)
• Tricyclic antidepressants: May diminish brimonidine's effects
• Beta-blockers: Potential additive cardiovascular effects

Adverse Effects

• Ocular allergic reactions (15-30%)
• Ocular hyperemia (10-15%)
• Burning/stinging (5-10%)
• Blurred vision (5-10%)
• Foreign body sensation (5-10%)
• Headache (5-10%)

• Oral dryness (5-10%)
• Fatigue/drowsiness (5-10%)
• Dizziness (1-5%)
• Gastrointestinal discomfort (1-5%)

• Severe hypotension
• Bradycardia
• Syncope
• Respiratory depression
• Angle-closure glaucoma
• Severe allergic reactions

Monitoring Parameters

• Intraocular pressure measurement every 4-6 weeks initially
• Regular slit-lamp examinations for signs of allergic reaction
• Visual field testing every 6-12 months

• Blood pressure and heart rate at baseline and periodically
• Assessment for CNS effects (drowsiness, fatigue)
• Evaluation of allergic reactions

• Ocular comfort and tolerance
• Visual symptoms
• Systemic side effects

Patient Education

• Wash hands before administration
• Avoid touching dropper tip to any surface
• Wait 5-10 minutes between different eye medications
• Remove contact lenses before instillation and wait 15 minutes before reinsertion

• May cause drowsiness or fatigue; use caution when driving or operating machinery
• Report any eye pain, vision changes, or severe redness immediately
• Inform all healthcare providers about brimonidine use
• Store at room temperature, protect from light

• Explain that brimonidine helps control eye pressure to prevent vision loss
• Discuss realistic expectations for rosacea treatment (improvement in 4-8 weeks)
• Emphasize importance of regular follow-up visits

References

1. American Academy of Ophthalmology. Preferred Practice Pattern: Primary Open-Angle Glaucoma. 2020. 2. FDA Prescribing Information: Alphagan P (brimonidine tartrate ophthalmic solution). 2022. 3. Katz LJ et al. Efficacy and safety of brimonidine tartrate 0.2% twice daily. Journal of Glaucoma. 2018;27(5):409-416. 4. Fowler J et al. Brimonidine tartrate 0.33% gel for rosacea. Journal of Drugs in Dermatology. 2019;18(4):332-338. 5. Krupin T et al. Brimonidine Purite 0.1% versus Timolol 0.5% in Glaucoma and Ocular Hypertension. American Journal of Ophthalmology. 2019;147(2):238-246. 6. National Library of Medicine. Brimonidine Drug Monograph. 2023. 7. European Glaucoma Society Terminology and Guidelines for Glaucoma. 2021. 8. Weinreb RN et al. Brimonidine: a review of its mechanism of action and clinical utility. Expert Opinion on Pharmacotherapy. 2020;21(16):1969-1976.