Schedule H

Ophthalmic (primary), Oral (limited use)

• Ophthalmic solution: 0.25%, 0.5% (5 mL, 10 mL multi-dose bottles)

• Ophthalmic gel-forming solution: 0.5%

• Oral tablets: 5 mg, 10 mg (limited availability)

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 0.25% solution in affected eye(s) twice daily

Titration If IOP reduction inadequate after 4 weeks, increase to 0.5% solution

Usual maintenance dose 1 drop of 0.25% or 0.5% solution twice daily

Maximum dose 1 drop of 0.5% solution twice daily per eye

Key Clinical Notes:

• Timolol 0.25% often sufficient; start with lower concentration especially in light-iris individuals

• Measure IOP 2–4 weeks after initiation to assess response

• Once-daily dosing with 0.5% may be adequate in some patients with good IOP control

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

• Response may diminish over time (long-term drift) — reassess periodically

▶ 2. Ocular Hypertension

Parameter Recommendation

Starting dose 1 drop of 0.25% solution in affected eye(s) twice daily

Titration Increase to 0.5% solution if target IOP not achieved

Usual maintenance dose 1 drop of 0.25% or 0.5% solution twice daily

Maximum dose 1 drop of 0.5% solution twice daily per eye

Key Clinical Notes:

• Used for elevated IOP without optic disc changes or visual field loss

• Treatment decision based on individual risk assessment

• Monitor for progression to glaucoma

▶ 3. Secondary Glaucomas (Adjunctive Therapy)

Parameter Recommendation

Starting dose 1 drop of 0.25% or 0.5% solution twice daily

Titration Adjust based on IOP response; combine with other anti-glaucoma agents as needed

Usual maintenance dose 1 drop twice daily

Maximum dose 1 drop of 0.5% solution twice daily per eye

Key Clinical Notes:

• Used adjunctively in neovascular glaucoma, uveitic glaucoma, aphakic/pseudophakic glaucoma

• Often combined with prostaglandin analogues, carbonic anhydrase inhibitors, or alpha-2 agonists

• Fixed-dose combinations available for improved compliance

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Migraine Prophylaxis (Oral) — OFF-LABEL Starting: 10 mg/day (5 mg twice daily); Titration: Increase to 10 mg twice daily if needed; Maximum: 30 mg/day Evaluate response at 8–12 weeks; continue long-term if effective Specialist only (neurology); Evidence: International RCTs; occasionally used in Indian neurology practice; propranolol preferred first-line

Essential Hypertension (Oral) — OFF-LABEL Starting: 10 mg/day; Usual: 20–40 mg/day in 1–2 divided doses; Maximum: 60 mg/day Long-term Rarely used; cardioselective beta-blockers (metoprolol, bisoprolol) preferred in Indian practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

▶ 1. Paediatric Glaucoma (Congenital, Juvenile)

Parameter Recommendation

Starting dose 1 drop of 0.25% solution in affected eye(s) twice daily

Titration May increase to 0.5% solution if inadequate response under close monitoring

Usual maintenance dose 1 drop of 0.25% or 0.5% twice daily

Maximum dose 1 drop of 0.5% twice daily per eye

Key Clinical Notes:

• Use with extreme caution in neonates and infants — significant systemic absorption possible

• Prefer 0.25% concentration in young children

• Monitor for systemic beta-blockade: bradycardia, apnoea, bronchospasm, hypoglycaemia

• Punctal occlusion essential after instillation

Safety Monitoring (All Paediatric Ophthalmic Use):

• Heart rate monitoring before and after initiation

• Observe for respiratory symptoms (especially in neonates)

• Blood glucose monitoring in neonates/infants (risk of hypoglycaemia)

• Regular IOP and optic nerve assessment

⚠️ Use with extreme caution in neonates; avoid unless prescribed by paediatric ophthalmology specialist

Secondary Indications — Paediatrics (Off-label)

Indication Age Dose Duration Notes

Infantile Haemangioma (Oral Timolol) — OFF-LABEL >1 month Starting: 0.25 mg/kg twice daily orally; Titration: Increase gradually every 1–2 weeks; Maintenance: 0.5–1 mg/kg twice daily; Maximum: 2 mg/kg/day 6–12 months; until involution Specialist only (paediatric dermatology + cardiology); Evidence: RCTs and case series; propranolol preferred first-line

Infantile Haemangioma (Topical Timolol Gel) — OFF-LABEL >1 month 1 drop of 0.5% gel-forming solution applied topically to lesion twice daily Until involution or adequate response Specialist only; Evidence: Case series; used for superficial/small lesions

No dose adjustment required for ophthalmic formulations.

For oral timolol (limited use):

• Mild to moderate impairment: No adjustment required

• Severe impairment (eGFR <30 mL/min): Use with caution; start at lower dose

• Bronchial asthma or history of bronchospasm

• Severe chronic obstructive pulmonary disease (COPD)

• Sinus bradycardia (HR <50 bpm)

• Second- or third-degree atrioventricular block (without pacemaker)

• Uncompensated cardiac failure

• Cardiogenic shock

• Known hypersensitivity to timolol or any formulation component

• Severe peripheral arterial circulatory disorders

• Mild to moderate COPD — use with caution; consider alternative agents

• Diabetes mellitus — may mask symptoms of hypoglycaemia (tachycardia, tremor)

• Thyrotoxicosis — may mask tachycardia; abrupt withdrawal may precipitate thyroid storm

• Peripheral vascular disease

• Myasthenia gravis — beta-blockers may worsen symptoms

• History of atopy or severe anaphylactic reactions — may increase sensitivity to allergens

• Corneal disease or dry eye syndrome — chronic use may worsen ocular surface disease

• Concurrent use of other beta-blockers (systemic or topical) — additive systemic effects

• First-degree AV block

• Prinzmetal's angina

• Depression or psychiatric illness

• Phaeochromocytoma (only with alpha-blockade)

• Abrupt withdrawal of oral timolol — taper gradually to avoid rebound effects

Aspect Details

Risk category Limited human data; potential for fetal beta-blockade with systemic absorption

Safety statement Use only if potential benefit justifies potential risk to fetus

Preferred alternatives Brimonidine 0.2% (after first trimester) may have lower systemic absorption; discuss with ophthalmology

When to use May be continued if essential for IOP control; use lowest effective concentration with punctal occlusion

Monitoring Fetal heart rate; neonatal monitoring for bradycardia, hypoglycaemia, respiratory depression at delivery

Aspect Details

Compatibility Ophthalmic timolol: Likely compatible with breastfeeding (minimal systemic absorption with proper technique)

Drug levels in milk Low with ophthalmic use; moderate with oral use

Preferred alternatives Consider brimonidine with caution; ensure punctal occlusion to minimise absorption

Oral timolol Avoid or use with caution — excreted in breast milk

Infant monitoring Observe for bradycardia, poor feeding, lethargy, respiratory symptoms

Aspect Recommendation

Starting dose 0.25% ophthalmic solution preferred initially

Titration Titrate slowly; assess systemic effects before increasing concentration

Extra risks Higher risk of systemic absorption and adverse effects; increased sensitivity to beta-blockade (bradycardia, hypotension, fatigue); fall risk due to dizziness; may worsen depression

Special considerations Punctal occlusion technique essential; assess cardiovascular status before initiation; consider once-daily gel formulation for better compliance

Interacting Drug Mechanism / Effect Management

Verapamil, Diltiazem (oral) Additive negative chronotropic and dromotropic effects; severe bradycardia and AV block Avoid combination; if essential, monitor ECG and heart rate closely

Other beta-blockers (systemic or ophthalmic) Additive systemic beta-blockade; excessive bradycardia and hypotension Avoid combining multiple beta-blockers

Clonidine Rebound hypertension risk if clonidine withdrawn while on beta-blocker If discontinuing, taper clonidine after stopping beta-blocker

Amiodarone Additive negative chronotropic effect; severe bradyarrhythmia Use with extreme caution; ECG monitoring

Flecainide, Propafenone Additive negative inotropic and dromotropic effects Avoid or use with caution; monitor cardiac function

MAO inhibitors Potential for severe hypertensive crisis Avoid combination

Interacting Drug Mechanism / Effect Management

Insulin, oral hypoglycaemics Beta-blockers may mask hypoglycaemia symptoms (tachycardia, tremor) Monitor blood glucose closely; educate patient about non-masked symptoms (sweating)

Digoxin Additive effect on AV conduction Monitor heart rate and ECG

Adrenaline (epinephrine) Reduced efficacy of adrenaline in anaphylaxis; paradoxical hypertension possible Higher doses of adrenaline may be required in emergency; consider glucagon

NSAIDs May reduce antihypertensive effect of systemic beta-blockers Monitor blood pressure (mainly relevant for oral timolol)

Quinidine May increase timolol levels (CYP2D6 inhibition) Monitor for bradycardia

Reserpine, guanethidine Additive hypotension and bradycardia Use with caution; monitor

Ocular (with ophthalmic use):

• Ocular irritation, burning, stinging

• Dry eyes

• Blurred vision (transient)

• Foreign body sensation

• Conjunctival hyperaemia

• Superficial punctate keratitis

Systemic (due to absorption):

• Fatigue / lethargy

• Headache

• Dizziness

• Bradycardia (usually asymptomatic)

• Cold extremities

Adverse Effect Clinical Action

Bronchospasm / asthma exacerbation Discontinue immediately; do not rechallenge; treat with bronchodilators

Symptomatic bradycardia Discontinue; assess need for atropine or pacemaker if severe

Severe hypotension Discontinue; supportive care

Heart block (second/third degree) Discontinue; cardiology referral

Cardiac failure (new or worsening) Discontinue; manage heart failure

Severe allergic reaction / anaphylaxis Discontinue; emergency management

CNS effects (depression, confusion, hallucinations) Rare; discontinue if significant

Apnoea in neonates/infants Discontinue immediately; supportive care

Stevens-Johnson Syndrome Very rare; discontinue; supportive care

After initiation (2–4 weeks) IOP measurement; heart rate; enquire about systemic symptoms (fatigue, dizziness, dyspnoea)

Periodic (every 3–6 months) IOP; visual field testing (annually or as indicated); optic nerve evaluation; reassess systemic symptoms

Paediatric use Heart rate and respiratory status at each visit; blood glucose in neonates/infants

Glucomol 0.25%, 0.5% eye drops Allergan

Iotim 0.25%, 0.5% eye drops FDC

Timolet 0.5% eye drops Sun Pharma

Nyolol 0.25%, 0.5% eye drops Novartis

Ocupres 0.25%, 0.5% eye drops Cipla

Timoptic 0.25%, 0.5% eye drops MSD

Common FDCs:

NLEM Status Timolol 0.5% eye drops included in NLEM 2022 Price regulated by NPPA

Government Supply Available through government eye hospitals and PHCs At subsidised rates

• Punctal occlusion technique is essential: Instruct patients to press on the inner corner of the eye (nasolacrimal duct area) for 1–2 minutes after instillation to minimise systemic absorption — particularly important in elderly, cardiac patients, and children

• Avoid in asthma/COPD even with topical use: Even ophthalmic timolol can cause fatal bronchospasm in susceptible patients; use prostaglandin analogues (latanoprost) as first-line in these patients

• Long-term drift phenomenon: IOP-lowering effect may diminish over years; regular monitoring and treatment adjustment needed

• Consider preservative-free formulations: For patients with chronic dry eye or ocular surface disease; benzalkonium chloride in multi-dose bottles may exacerbate symptoms

• FDCs improve compliance: For patients requiring multiple agents, fixed-dose combinations reduce dosing frequency and improve adherence

• Systemic effects can occur unpredictably: Even with ophthalmic use, monitor for fatigue, bradycardia, and exercise intolerance — especially in elderly patients

Timolol; beta-blocker; glaucoma; ocular hypertension; ophthalmology; IOP reduction; ophthalmic drops; systemic absorption; asthma-contraindicated; infantile haemangioma; NLEM India; Schedule H

RxIndia v1.0 — 03 May 2025

• CDSCO approved product information

• Indian Pharmacopoeia

• NLEM India 2022

• API Textbook of Medicine, 11th Edition

• AIIMS Ophthalmology Treatment Protocols

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• All India Ophthalmological Society — Glaucoma Management Guidelines

• IAP Guidelines for Infantile Haemangioma (for off-label paediatric use)

• International RCTs (for off-label migraine prophylaxis)