Alphagan P

Ophthalmic Use (Approved):

• Open-angle glaucoma: To reduce intraocular pressure (IOP) in patients with open-angle glaucoma.
• Ocular hypertension: As monotherapy or adjunctive therapy to lower elevated IOP.

Topical Dermatologic Use (Approved):

• Rosacea (Facial Erythema): Topical gel formulation is approved for persistent facial erythema of rosacea in adults.

Off-label Uses (Clinically Accepted):

• Prevention of intraoperative/postoperative IOP spikes: Used perioperatively in laser eye surgery (e.g., LASIK, PRK).
• Neuroprotective agent in glaucoma: Investigational for potential retinal ganglion cell protection (not FDA-approved).
• Adjunctive therapy in angle-closure glaucoma (as part of preoperative medical management).

Ophthalmic Solution (0.1%, 0.15%, 0.2%):

• Adults and Adolescents (≥2 years):
  Instill 1 drop in the affected eye(s) twice daily, approximately 12 hours apart.
• Children (<2 years): Not recommended due to serious CNS depression risk.
• Elderly: No dosage adjustment required; monitor for hypotension or bradycardia.
• Renal/Hepatic Impairment:
  No specific dose adjustments, but use cautiously; limited clinical data available.

Topical Gel (0.33%):

• Adults (≥18 years):
  Apply a pea-sized amount once daily to the entire face, avoiding eyes, lips, and mucous membranes. Wash hands after application.
• Pediatric Use: Not approved for individuals <18 years for rosacea.

Brimonidine tartrate is a selective alpha-2 adrenergic receptor agonist. In the eye, it reduces intraocular pressure by decreasing aqueous humor production and enhancing uveoscleral outflow. Topically, in rosacea, it causes vasoconstriction of superficial blood vessels, resulting in a reduction in persistent facial erythema. Its dual mechanism of action enables both pressure-lowering effects in glaucoma and visible vasoconstrictive effects in erythematous skin conditions.

• Absorption:
  Ophthalmic absorption occurs through the conjunctiva and nasal mucosa. Topical absorption through facial skin is minimal but sufficient for therapeutic effect.
• Bioavailability:
  Systemic bioavailability is approximately 38% after ophthalmic administration.
• Onset of Action:
• Ophthalmic: Within 1 hour.
• Topical (rosacea): Within 30 minutes.
• Peak Plasma Concentration: Reached within 1–4 hours (ophthalmic route).
• Half-life: Approximately 2–3 hours.
• Metabolism:
  Primarily hepatic metabolism via aldehyde oxidase and CYP450 enzymes (minor).
• Excretion:
  Mainly via urine (~74%), as metabolites.

• Pregnancy:
  FDA Pregnancy Category B (for ophthalmic use).
  Animal studies have not shown fetal harm; however, adequate human studies are lacking. Topical gel data are limited — use only if clearly needed.
• Lactation:
  Brimonidine is excreted in small amounts into breast milk after ophthalmic use. The risk to a breastfeeding infant is considered low, but caution is advised. Avoid direct topical exposure on breast or chest area to prevent oral ingestion by infant.
• Recommendation:
  Use with caution in pregnant or breastfeeding women; avoid in neonates and infants due to risk of CNS depression.

• Primary Class:
  Alpha-2 Adrenergic Receptor Agonist
• Subclasses:
• Ophthalmic hypotensive agent (glaucoma therapy)
• Topical vasoconstrictor (for rosacea-induced erythema)

• Hypersensitivity to Brimonidine Tartrate or excipients
• Use in neonates and infants (<2 years of age) due to risk of apnea, hypotension, and coma
• Concurrent use with monoamine oxidase inhibitors (MAOIs)

• Pediatric Risk: Serious CNS depression has occurred in children under 2 years (avoid use).
• Cardiovascular Effects: May cause hypotension or bradycardia; caution in patients with cardiovascular disease.
• CNS Effects: Drowsiness, fatigue, and dizziness may occur; avoid operating heavy machinery.
• Depression Risk: Use cautiously in patients with a history of depression.
• Allergic Reactions: Ocular allergy or follicular conjunctivitis may develop with chronic use.
• Rosacea Gel Use: Avoid application on open wounds or broken skin.

Common Adverse Effects:

• Ophthalmic Use:
• Eye: Ocular hyperemia, dry eyes, burning/stinging, blurred vision, allergic conjunctivitis, foreign body sensation
• CNS: Fatigue, somnolence, dizziness, headache
• Topical Use (Rosacea):
• Skin: Erythema worsening, burning, flushing, pruritus, skin irritation

Serious/Rare Effects:

• Hypotension, bradycardia
• Severe allergic reactions (anaphylaxis, angioedema)
• CNS depression (especially in children)
• Syncope

• MAO Inhibitors (e.g., phenelzine, tranylcypromine): May cause hypertensive crisis or severe hypotension—contraindicated.
• Tricyclic Antidepressants: May blunt antihypertensive or IOP-lowering effects.
• CNS Depressants (alcohol, benzodiazepines, opioids): Increased risk of sedation.
• Beta-blockers and Antihypertensives: Additive hypotensive or bradycardic effects.
• Enzymes Involved: Minor hepatic metabolism via CYP450 and aldehyde oxidase pathways.

• EMA and FDA approvals continue to support both ophthalmic and topical uses with no major restrictions.
• Recent label updates include stronger warnings against pediatric use (<2 years) and improved allergy risk communication.
• Clinical guidelines for glaucoma still consider Brimonidine a first-line or adjunctive agent for IOP control, particularly when beta-blockers are contraindicated.

• Ophthalmic Solution:
• Store at 15°C to 25°C (59°F to 77°F)
• Protect from light and moisture
• Keep bottle tightly closed and avoid contamination
• Topical Gel:
• Store at 20°C to 25°C
• Do not freeze
• Keep away from excessive heat and direct sunlight