Schedule H

Ophthalmic (topical)

• Ophthalmic solution: 0.1% w/v (5 mL bottle)

• Ophthalmic solution: 0.15% w/v (5 mL bottle)

• Ophthalmic solution: 0.2% w/v (5 mL bottle)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

▶ 1. Primary Open-Angle Glaucoma (POAG)

Parameter Recommendation

Starting dose 1 drop of 0.15% or 0.2% solution in affected eye(s) twice daily (approximately 12 hours apart)

Titration May increase to three times daily if IOP control inadequate after 2–4 weeks

Usual maintenance dose 1 drop twice daily

Maximum dose 1 drop three times daily per eye

Key Clinical Notes:

• Onset of IOP-lowering effect: 1–2 hours; peak effect at 2–3 hours

• Duration of effect: approximately 12 hours

• May be used as monotherapy or adjunctive to other antiglaucoma agents (beta-blockers, prostaglandin analogues, carbonic anhydrase inhibitors)

• Lower concentration (0.1%, 0.15%) may have better tolerability with similar efficacy to 0.2%

• Apply nasolacrimal occlusion for 1–2 minutes after instillation to minimise systemic absorption

▶ 2. Ocular Hypertension

Parameter Recommendation

Starting dose 1 drop of 0.15% or 0.2% solution in affected eye(s) twice daily

Titration May increase to three times daily if target IOP not achieved

Usual maintenance dose 1 drop twice daily

Maximum dose 1 drop three times daily per eye

Key Clinical Notes:

• Treatment decision based on baseline IOP and individual risk assessment

• Monitor for progression to glaucoma

• Reassess IOP at 2–4 weeks after initiation

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Prevention of IOP Spike Post-Laser Procedures (trabeculoplasty, iridotomy) — OFF-LABEL 1 drop 0.2% 1 hour before and immediately after laser procedure Single use (perioperative) Specialist only; Evidence: Clinical studies; commonly used in Indian ophthalmology practice

Lid Retraction in Thyroid Eye Disease (mild cases) — OFF-LABEL 1 drop 0.1% or 0.15% once or twice daily Variable; assess response Specialist only; Evidence: Case series; limited use in Indian practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

⛔ Brimonidine is CONTRAINDICATED in infants and children <2 years of age due to risk of severe CNS depression, including apnoea, hypotension, bradycardia, hypothermia, and unresponsiveness.

Secondary Indications — Paediatrics (Off-label)

▶ Paediatric Glaucoma (Children ≥2 years) — OFF-LABEL

2–7 years 1 drop of 0.1% solution in affected eye(s) twice daily Use with extreme caution; higher risk of CNS effects

7 years 1 drop of 0.1% or 0.15% solution in affected eye(s) twice daily Maximum: 1 drop twice daily

Key Clinical Notes:

• Not a first-line agent in paediatric glaucoma

• Use only when other options (surgery, prostaglandin analogues, beta-blockers) are unsuitable or have failed

• Prefer lower concentration (0.1%) to minimise systemic absorption

• Paediatric ophthalmology specialist supervision mandatory

Safety Monitoring (Essential in All Paediatric Use):

• Monitor level of consciousness and alertness

• Observe for somnolence, lethargy, hypotonia

• Monitor respiratory rate (risk of respiratory depression)

• Assess feeding behaviour (poor feeding may indicate toxicity)

• Check heart rate and blood pressure

• Parents must be counselled on warning signs

⚠️ Absolutely contraindicated in children <2 years — risk of life-threatening CNS and respiratory depression

No dose adjustment required.

Brimonidine has minimal systemic absorption following ophthalmic administration; no clinically significant renal elimination.

• Known hypersensitivity to brimonidine tartrate or any component of the formulation

• Neonates and infants <2 years of age (life-threatening CNS depression risk)

• Concurrent use with monoamine oxidase inhibitors (MAOIs) — risk of hypertensive crisis or exaggerated CNS effects

• Concurrent use with tricyclic antidepressants — may antagonise brimonidine's hypotensive effect and interfere with its IOP-lowering action

• Children aged 2–7 years — increased susceptibility to CNS adverse effects; use with extreme caution

• Low body weight children — higher risk of systemic toxicity

• Severe cardiovascular disease (coronary insufficiency, Raynaud's phenomenon, orthostatic hypotension, thromboangiitis obliterans)

• Cerebrovascular insufficiency

• Depression — may worsen with alpha-2 agonist therapy

• Hepatic impairment — brimonidine is metabolised by the liver

• Renal impairment — use with caution in severe impairment

• Contact lens wear — remove lenses before instillation; wait at least 15 minutes before reinserting (benzalkonium chloride may be absorbed by soft lenses)

• Dry eye disease or ocular surface disorders — preservative may exacerbate symptoms

• History of vasovagal episodes

• Concurrent use of CNS depressants — additive sedation risk

Aspect Details

Risk category Limited human data; animal studies show fetal toxicity at high doses; use with caution

Safety statement Avoid during pregnancy unless benefit clearly outweighs potential risk

Preferred alternatives Timolol (more pregnancy safety data); latanoprost (limited data but commonly used); specialist ophthalmology input essential

When to use Only if no safer alternative and IOP control is critical to prevent vision loss

Monitoring Maternal blood pressure monitoring (systemic absorption may cause hypotension); fetal well-being assessment

Aspect Details

Compatibility Use with caution — limited human data

Drug levels in milk Unknown; likely low due to minimal systemic absorption with proper technique

Preferred alternatives Timolol ophthalmic (more established lactation safety data)

Recommendations Use nasolacrimal occlusion technique to minimise systemic absorption; use lowest effective dose and concentration

Infant monitoring Observe for sedation, lethargy, poor feeding, respiratory depression

Aspect Recommendation

Starting dose Same as younger adults — 1 drop twice daily

Titration Avoid more frequent dosing due to increased sensitivity to systemic effects

Extra risks Increased susceptibility to hypotension, bradycardia, fatigue, and drowsiness; may worsen pre-existing orthostatic hypotension; increased fall risk

Special considerations Ensure proper drop instillation technique with nasolacrimal occlusion; assess cardiovascular status before initiation; monitor blood pressure periodically

Interacting Drug Mechanism / Effect Management

Monoamine oxidase inhibitors (MAOIs) — phenelzine, tranylcypromine, selegiline, moclobemide Risk of hypertensive crisis; enhanced sympathomimetic effects CONTRAINDICATED — do not use concurrently

Tricyclic antidepressants (amitriptyline, imipramine, nortriptyline) May antagonise brimonidine's hypotensive and IOP-lowering effects; reduced efficacy CONTRAINDICATED — avoid concurrent use

CNS depressants (benzodiazepines, opioids, barbiturates, alcohol) Additive CNS depression; sedation, drowsiness, respiratory depression Avoid combination or use with extreme caution; warn patients about additive sedation

Other alpha-2 agonists (clonidine, tizanidine, dexmedetomidine) Additive hypotension, bradycardia, and CNS depression Avoid concurrent use if possible

Interacting Drug Mechanism / Effect Management

Antihypertensives (beta-blockers, calcium channel blockers, ACE inhibitors) Possible additive hypotension Monitor blood pressure; may need dose adjustment of antihypertensive

Cardiac glycosides (digoxin) Additive bradycardia Monitor heart rate

Other topical antiglaucoma agents Increased local ocular side effects; potential systemic additive effects with beta-blockers Stagger administration by at least 5 minutes; monitor for systemic effects

Miotic agents (pilocarpine) May have additive IOP-lowering effect but also increased miosis Can be used together with monitoring

Note: When using multiple ophthalmic medications, administer drops at least 5 minutes apart to ensure adequate absorption.

Ocular (most common):

• Allergic conjunctivitis (10–25%) — often delayed onset (after 3–6 months of use)

• Conjunctival hyperaemia (ocular redness)

• Eye pruritus (itching)

• Ocular burning/stinging on instillation

• Dry eye sensation

• Foreign body sensation

• Blurred vision (transient)

• Eyelid oedema or erythema

• Blepharitis

• Follicular conjunctivitis

Systemic (due to absorption):

• Dry mouth (xerostomia)

• Fatigue/drowsiness

• Headache

Adverse Effect Clinical Action

Severe allergic conjunctivitis with follicular response Discontinue brimonidine; switch to alternative antiglaucoma agent; may require topical steroids for severe inflammation

Severe CNS depression in children (somnolence, hypotonia, apnoea, unresponsiveness) MEDICAL EMERGENCY — discontinue immediately; supportive care; may require hospitalisation and intensive monitoring

Symptomatic hypotension / syncope Discontinue; assess cardiovascular status; avoid rechallenge

Severe bradycardia Discontinue; cardiology evaluation if symptomatic

Respiratory depression (especially in young children) Discontinue immediately; emergency management

Iritis / anterior uveitis (rare) Discontinue; ophthalmology evaluation

After initiation (2–4 weeks) IOP measurement to assess response; enquire about ocular symptoms (redness, itching, irritation)

Periodic (every 3–6 months) IOP; ocular surface examination; assess for signs of delayed allergic conjunctivitis (especially between 3–12 months of use)

Paediatric use Level of consciousness; respiratory rate; heart rate; feeding behaviour; blood pressure — assess at each visit and educate parents on warning signs

Brand Name Concentration Manufacturer

Alphagan P 0.15% Allergan/AbbVie

Alphagan 0.2% Allergan/AbbVie

Brimodin 0.2% Ajanta Pharma

Brimopress 0.15% Cipla

Brimolol 0.15% Sun Pharma

Glauconex B 0.2% Entod

Common FDCs:

NLEM Status Brimonidine + Timolol FDC included in NLEM 2022 Price regulated by NPPA

Government Supply Available through government eye hospitals At subsidised rates

• Nasolacrimal occlusion technique is essential: Instruct patients to press on the inner corner of the eye for 1–2 minutes after instillation to minimise systemic absorption — particularly important in children and elderly

• Delayed allergic conjunctivitis is common: Typically develops after 3–6 months of continuous use; presents with itching, redness, and follicular response; may require switching to alternative agent

• Absolutely avoid in children <2 years: Risk of life-threatening CNS depression (apnoea, hypotension, bradycardia, hypothermia); even accidental exposure requires medical evaluation

• Lower concentrations may be better tolerated: 0.1% and 0.15% formulations (preserved with Purite instead of benzalkonium chloride in some brands) may have lower incidence of ocular allergy with similar efficacy

• Excellent adjunctive agent: Combines well with prostaglandin analogues and beta-blockers; FDCs available for improved compliance

• Consider in patients with asthma/COPD: Unlike beta-blockers, brimonidine is safe in patients with bronchospastic disease and can be used when topical beta-blockers are contraindicated

Brimonidine; alpha-2 agonist; glaucoma; ocular hypertension; ophthalmology; IOP reduction; paediatric-contraindicated-under-2-years; allergic conjunctivitis; CNS depression risk; NLEM FDC; Schedule H

RxIndia v1.0 — 10 Apr 2025

• CDSCO approved product information

• Indian Pharmacopoeia

• NLEM India 2022

• API Textbook of Medicine, 11th Edition

• AIIMS Ophthalmology Treatment Protocols

• All India Ophthalmological Society — Glaucoma Management Guidelines

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• IAP Guidelines — Paediatric Glaucoma (for paediatric contraindication and off-label use context)

• Indian tertiary ophthalmic institution protocols