Schedule H

Ophthalmic (Topical)

• Ophthalmic suspension: 1% w/v (5 mL, 10 mL bottles)

Fixed-Dose Combinations Available:

• Brinzolamide 1% + Brimonidine 0.2% ophthalmic suspension

• Brinzolamide 1% + Timolol 0.5% ophthalmic suspension

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Primary Open-Angle Glaucoma — Adults

Parameter Recommendation

Starting dose 1 drop into affected eye(s) twice daily

Titration May increase to 1 drop three times daily if IOP control inadequate

Usual maintenance dose 1 drop twice daily

Maximum dose 1 drop three times daily

Clinical Notes:

• Shake suspension well before each use to ensure uniform drug distribution

• May be used as monotherapy or as adjunct to beta-blockers, prostaglandin analogues, or alpha-agonists

• Allow 5–10 minutes between instillation of different ophthalmic medications

• Apply nasolacrimal occlusion after instillation to reduce systemic absorption

1. Ocular Hypertension — Adults

Parameter Recommendation

Starting dose 1 drop into affected eye(s) twice daily

Titration May increase to 1 drop three times daily if target IOP not achieved

Usual maintenance dose 1 drop twice daily

Maximum dose 1 drop three times daily

Clinical Notes:

• Target IOP reduction typically 15–20% from baseline

• Assess IOP response at 2–4 weeks

• Consider combination therapy if monotherapy inadequate

Secondary Indications — Adults (Off-label)

Not applicable — No significant off-label indications documented in Indian practice.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Not routinely approved for paediatric use due to limited safety and efficacy data.

Secondary Indications — Paediatric (Off-label)

Indication Dose Notes

Paediatric Glaucoma (Primary congenital, juvenile open-angle) 1 drop into affected eye(s) twice daily OFF-LABEL • Specialist only • Paediatric ophthalmologist supervision mandatory

Age Restrictions:

• Not recommended in children <4 years except under specialist paediatric ophthalmology supervision

• Limited safety data in paediatric population

Safety Monitoring:

• Monitor for ocular discomfort and irritation

• Watch for systemic carbonic anhydrase inhibitor effects (rare with topical use): electrolyte imbalance, metabolic acidosis

• Assess IOP response at 2–4 weeks

• Monitor growth and development with long-term use

Notes:

• Although systemic absorption is low with topical use, brinzolamide and its metabolite are renally excreted

• In severe renal impairment, risk of metabolic acidosis and electrolyte disturbances

• If use is essential in moderate impairment, monitor serum electrolytes and acid-base status

• Known hypersensitivity to brinzolamide or any component of formulation

• History of severe hypersensitivity to sulfonamides (systemic or topical)

• Severe renal impairment (eGFR <30 mL/min)

• Hyperchloraemic acidosis

• History of sulfonamide allergy — cross-reactivity rare with topical use but possible

• Corneal endothelial compromise (Fuchs' endothelial dystrophy, low endothelial cell count) — risk of corneal oedema/decompensation

• Contact lens wearers — formulation contains benzalkonium chloride; remove lenses before instillation and wait ≥15 minutes before reinsertion

• Moderate renal impairment — monitor for systemic effects with prolonged use

• Elderly patients — more likely to have reduced renal function; assess before initiating

• Acute angle-closure glaucoma — not effective for acute management; requires definitive treatment

• Concurrent use of oral carbonic anhydrase inhibitors — additive systemic effects

Parameter Information

Risk Category Not formally classified in India; animal studies show some embryofetal risk

Overall Safety Avoid unless benefit clearly outweighs risk

Preferred Alternatives Timolol (topical beta-blocker) or latanoprost (prostaglandin analogue) — better safety data in pregnancy

When May Be Used Refractory glaucoma where other agents failed or contraindicated — ophthalmologist supervision mandatory

Monitoring Intraocular pressure; fetal growth surveillance with prolonged use

Parameter Information

Compatibility Likely compatible — low systemic absorption

Expected Milk Levels Low (minimal systemic absorption from topical use)

Preferred Alternatives Timolol (more safety data in lactation)

Decision May use if clearly indicated; weigh benefits vs theoretical risks

Infant Monitoring Poor feeding, vomiting, irritability (unlikely with topical use)

Parameter Recommendation

Starting dose Standard adult dosing (1 drop twice daily)

Titration Standard titration acceptable

Special considerations Higher prevalence of renal impairment — assess renal function before initiating

Extra monitoring Monitor for ocular irritation, blurred vision; assess for systemic effects in those with reduced renal reserve

Risk factors Often on multiple topical agents — increased risk of preservative toxicity; polypharmacy

Interacting Drug Effect & Mechanism Management

Oral carbonic anhydrase inhibitors (acetazolamide, methazolamide) Additive systemic carbonic anhydrase inhibition — risk of hypokalaemia, metabolic acidosis, paraesthesias Avoid concurrent use

High-dose salicylates (aspirin >3 g/day) Carbonic anhydrase inhibition may enhance salicylate toxicity (increased CNS penetration) Avoid combination if possible; if essential, monitor for salicylate toxicity

Interacting Drug Effect Management

Topiramate, zonisamide Additive carbonic anhydrase inhibition — risk of metabolic acidosis, nephrolithiasis Monitor for acidosis symptoms; consider alternative antiglaucoma agent

Thiazide and loop diuretics Additive hypokalaemia risk Monitor serum potassium periodically

Other topical ophthalmic agents Dilution and altered absorption if instilled simultaneously Allow 5–10 minutes between different eye drops

• Transient blurred vision (common immediately post-instillation)

• Bitter or unusual taste (dysgeusia)

• Ocular discomfort (stinging, burning, irritation)

• Foreign body sensation

• Dry eyes

• Ocular hyperaemia

• Ocular pruritus

• Dermatitis (periorbital)

Adverse Effect Clinical Action

Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis (rare — sulfonamide class effect) Immediate discontinuation; dermatology/ICU referral

Severe hypersensitivity reaction (angioedema, anaphylaxis) Immediate discontinuation; emergency management

Corneal oedema / Corneal decompensation Discontinue; ophthalmology assessment; may require corneal specialist input

Metabolic acidosis (with systemic absorption in renal impairment) Discontinue; correct acid-base status

After initiation (2–4 weeks) IOP measurement; assess symptom tolerance; ocular surface examination

Long-term IOP every 3–6 months; annual comprehensive eye examination; renal function annually in elderly or those with comorbidities; monitor for corneal changes

Monotherapy:

• Azopt (Novartis/Alcon)

• Brinzox (Sun Pharma)

• Brisight (Cipla)

• Brinzo (FDC)

• Brizolam (Entod)

• Zolamide (Allergan)

Fixed-Dose Combinations:

Note: Not included in NLEM 2022; not under NPPA price control. Available in some state glaucoma programmes.

• Shake suspension well before each use — brinzolamide is a suspension and requires adequate mixing for uniform dosing

• Better tolerated than dorzolamide — patients experiencing significant stinging/burning with dorzolamide may switch to brinzolamide with improved comfort

• Avoid combining two topical CAIs — do not use brinzolamide with dorzolamide; choose one agent

• Transient blurred vision is expected — counsel patients not to drive or operate machinery immediately after instillation

• Contact lens precaution — remove lenses before instillation (benzalkonium chloride preservative); wait at least 15 minutes before reinsertion

• Fixed-dose combinations improve adherence — consider FDC with timolol or brimonidine in patients requiring multiple agents for IOP control

Brinzolamide; antiglaucoma; carbonic anhydrase inhibitor; topical CAI; ocular hypertension; open-angle glaucoma; sulfonamide; IOP-lowering; ophthalmology; pregnancy-cauti

RxIndia v1.0 — 05 Jan 2025

• CDSCO Approved Drug Formulations Database

• Indian Pharmacopoeia 2022

• National Formulary of India 2021

• AIIMS Ophthalmology Glaucoma Treatment Protocols

• API Textbook of Medicine, 11th Edition (Glaucoma Management)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics, 13th Edition

• All India Ophthalmological Society (AIOS) Glaucoma Guidelines

• Manufacturer Product Inserts (India-licensed formulations)