Schedule H

Oral

Formulation Type Available Strengths

Immediate-release tablets 25 mg, 50 mg, 100 mg, 200 mg

Sprinkle capsules 15 mg, 25 mg, 50 mg

Note: Extended-release tablets and injectable (IV) formulations are NOT AVAILABLE in India.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Epilepsy — Monotherapy (Adults and Adolescents ≥10 years)

For partial-onset seizures and primary generalised tonic-clonic seizures

Parameter Recommendation

Starting dose 25 mg once daily at bedtime

Titration Increase by 25–50 mg every 1–2 weeks in two divided doses

Usual maintenance dose 100–200 mg twice daily (200–400 mg/day total)

Maximum dose 500 mg/day

Clinical notes:

• Slow titration essential to minimise cognitive and neuropsychiatric adverse effects

• Administer in divided doses (morning and evening)

• Can be taken with or without food

1. Epilepsy — Adjunctive Therapy (Adults)

For partial-onset seizures, primary generalised tonic-clonic seizures

Parameter Recommendation

Starting dose 25–50 mg once daily at bedtime

Titration Increase by 25–50 mg every 1–2 weeks

Usual maintenance dose 100–200 mg twice daily (200–400 mg/day total)

Maximum dose 400 mg/day as adjunct

Clinical notes:

• May allow dose reduction of concomitant antiepileptic drugs

• Monitor for drug interactions with enzyme-inducing AEDs

1. Lennox-Gastaut Syndrome — Adjunctive Therapy (Adults)

Parameter Recommendation

Starting dose 25 mg once daily at bedtime

Titration Increase by 25–50 mg every 1–2 weeks

Usual maintenance dose 200–400 mg/day in two divided doses

Maximum dose 400 mg/day

1. Migraine Prophylaxis (Adults)

Parameter Recommendation

Starting dose 25 mg once daily at bedtime

Titration Increase by 25 mg weekly

Usual maintenance dose 50–100 mg/day in two divided doses

Maximum dose 200 mg/day

Clinical notes:

• Evaluate efficacy after 2–3 months of treatment at target dose

• Not effective for acute migraine treatment

• Consider alternative if no benefit after adequate trial

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes Evidence

Bipolar disorder (mood stabilisation adjunct) Starting: 25 mg/day; Target: 100–200 mg/day in divided doses Long-term maintenance OFF-LABEL; Specialist only Meta-analyses; Indian psychiatric practice

Alcohol use disorder (craving reduction) Starting: 25 mg/day; Target: 150–300 mg/day in divided doses Minimum 3–6 months OFF-LABEL; Addiction specialist only RCTs showing modest efficacy

Obesity (adjunct to lifestyle modification) Starting: 25 mg/day; Target: 50–100 mg/day Variable OFF-LABEL; Specialist obesity clinics only RCTs in combination therapy

Essential tremor Starting: 25 mg/day; Target: 50–400 mg/day Trial 8–12 weeks OFF-LABEL; Specialist only Limited RCT evidence

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Epilepsy — Monotherapy (Children ≥10 years)

For partial-onset and primary generalised tonic-clonic seizures

Parameter Recommendation

Starting dose 0.5–1 mg/kg/day once daily at bedtime (max 25 mg/day initial)

Titration Increase by 0.5–1 mg/kg/day every 1–2 weeks

Usual maintenance dose 3–6 mg/kg/day in two divided doses

Maximum dose 500 mg/day

1. Epilepsy — Adjunctive Therapy (Children ≥2 years)

Age/Weight Starting Dose Titration Usual Maintenance Maximum

2–16 years 1–3 mg/kg/day once daily at bedtime (max 25 mg) Increase by 1–3 mg/kg/day every 1–2 weeks 5–9 mg/kg/day in two divided doses 400 mg/day

1. Lennox-Gastaut Syndrome — Adjunctive Therapy (Children ≥2 years)

Parameter Recommendation

Starting dose 1 mg/kg/day once daily at bedtime

Titration Increase by 1–3 mg/kg/day every 1–2 weeks

Usual maintenance dose 5–9 mg/kg/day in two divided doses

Maximum dose 400 mg/day

Safety Monitoring in Paediatrics:

• Monitor growth parameters (height, weight) at each visit — growth suppression may occur

• Assess cognitive function and academic performance regularly

• Monitor for oligohidrosis and hyperthermia, especially in warm climates

• Serum bicarbonate periodically — metabolic acidosis risk higher in children

• Counsel caregivers on adequate hydration to prevent nephrolithiasis

Secondary Indications — Paediatric (Off-label)

Indication Age Notes Evidence

Migraine prophylaxis ≥12 years only OFF-LABEL; Paediatric neurologist supervision Limited paediatric data

Infantile spasms (refractory) Specialist only OFF-LABEL; Tertiary centres only Case series

Important statements:

• Not recommended below 2 years of age due to limited safety data and increased risk of hyperammonaemia and metabolic acidosis

• Sprinkle capsule formulation preferred for young children — can be opened and contents sprinkled on soft food

• Do not crush tablets

• Known hypersensitivity to topiramate or any excipient

• Metabolic acidosis in patients concurrently taking metformin

• Recent alcohol intake (within 6 hours before or after topiramate) — for extended-release formulations (not applicable in India as ER not available)

• History of nephrolithiasis — topiramate increases stone formation risk

• Pre-existing cognitive impairment or learning disability — may worsen

• Depression, suicidal ideation, or psychiatric history — monitor closely

• Acute myopia and secondary angle-closure glaucoma — discontinue immediately if sudden vision changes or eye pain

• Oligohidrosis and hyperthermia risk — especially in children and hot climates

• Metabolic acidosis — particularly with prolonged use, renal impairment, or concurrent valproate

• Pregnancy — significant teratogenic risk

• Concurrent use with other carbonic anhydrase inhibitors (acetazolamide)

• Osteoporosis risk with long-term use

• Patients on ketogenic diet — additive acidosis risk

Parameter Recommendation

Overall safety Teratogenic — associated with increased risk of oral clefts (cleft lip/palate); Category D equivalent

Preferred alternative Lamotrigine or levetiracetam (for epilepsy); propranolol or amitriptyline (for migraine prophylaxis)

When may be used Only if no effective alternative and seizure control is essential; shared decision with neurologist and obstetrician

What to monitor High-dose folic acid (4–5 mg/day) preconceptionally and during first trimester; detailed fetal anomaly scan at 18–20 weeks; fetal growth monitoring

Important: Counsel all women of childbearing potential on contraception requirements and teratogenic risks before initiating therapy.

Parameter Recommendation

Compatibility Compatible with breastfeeding with monitoring; use with caution

Preferred alternative Lamotrigine, levetiracetam (if equally effective for indication)

Drug levels in milk Low to moderate (infant receives ~3–23% of maternal weight-adjusted dose)

Infant monitoring Sedation, irritability, poor feeding, diarrhoea, poor weight gain

Parameter Recommendation

Starting dose 25 mg once daily at bedtime

Titration Slower titration — increase every 2–3 weeks

Special risks Increased sensitivity to cognitive effects (memory impairment, confusion); falls risk due to dizziness/ataxia; reduced renal clearance requiring dose adjustment

Additional considerations Assess baseline renal function before initiation; monitor for metabolic acidosis; ensure adequate hydration

Interacting Drug Effect / Risk Recommendation

Valproate Increased risk of hyperammonaemia and encephalopathy Monitor ammonia levels; observe for lethargy, confusion, vomiting

Combined oral contraceptives (ethinylestradiol) Topiramate ≥200 mg/day reduces oestrogen levels by ~30% — contraceptive failure risk Use alternative or additional contraception (barrier method or higher-dose OC)

Carbonic anhydrase inhibitors (acetazolamide, dorzolamide) Additive risk of metabolic acidosis and nephrolithiasis Avoid combination if possible

CNS depressants (benzodiazepines, opioids, alcohol) Additive sedation and cognitive impairment Use with caution; reduce doses if necessary

Phenytoin Mutual interaction — phenytoin increases topiramate clearance; topiramate may increase phenytoin levels Monitor phenytoin levels; may need topiramate dose increase

Interacting Drug Effect / Risk Recommendation

Carbamazepine Enzyme induction — reduces topiramate levels by ~40% May require increased topiramate dose; monitor seizure control

Phenobarbital, primidone Enzyme induction — reduced topiramate efficacy May require dose adjustment

Lithium Variable effect on lithium levels Monitor lithium levels when initiating or changing topiramate dose

Metformin May increase metformin levels; additive acidosis risk Monitor for lactic acidosis; check bicarbonate periodically

Digoxin Modest reduction in digoxin levels Monitor digoxin levels if clinically significant

Pioglitazone Reduced pioglitazone exposure Monitor glycaemic control

Hydrochlorothiazide May increase topiramate levels Monitor for topiramate adverse effects

• Paraesthesia (very common — tingling in extremities)

• Fatigue, somnolence

• Dizziness

• Cognitive dysfunction (word-finding difficulty, memory impairment, concentration problems)

• Anorexia, weight loss

• Nausea

• Taste perversion (dysgeusia — especially carbonated beverages)

• Mood changes, nervousness

• Diarrhoea

• Insomnia

Adverse Effect Notes

Acute myopia and secondary angle-closure glaucoma Sudden onset blurred vision, eye pain, headache — typically within first month; discontinue immediately; urgent ophthalmology referral

Metabolic acidosis May be asymptomatic; hyperventilation, fatigue, anorexia in severe cases; check serum bicarbonate

Nephrolithiasis Increased risk due to carbonic anhydrase inhibition; counsel on adequate hydration

Oligohidrosis and hyperthermia Especially in children; reduced sweating may lead to heat stroke; avoid excessive heat exposure

Hyperammonaemic encephalopathy Especially with concurrent valproate; lethargy, vomiting, confusion; check ammonia levels

Suicidal ideation/behaviour Class effect of antiepileptics — monitor especially during early treatment

Stevens-Johnson Syndrome/TEN Rare; discontinue immediately if mucocutaneous reaction

Osteoporosis Long-term use may reduce bone mineral density

During titration Cognitive function and mood at each visit; symptoms of acidosis; vision changes

Long-term Serum bicarbonate every 6–12 months; growth parameters in children at each visit; weight periodically; bone density if prolonged use (>2 years); ophthalmologic review if visual symptoms

• Topamac (Janssen)

• Topamac Sprinkle (Janssen)

• Topnex (Sun Pharma)

• Topirol (Intas)

• Toperma (Dr. Reddy's)

• Topaz (Cipla)

• Epitop (Torrent)

• Nextop (Mankind)

• Multiple generic brands available

Notes:

• Listed under NLEM 2022 (for epilepsy) — price regulated by NPPA

• Available through government supply at subsidised rates

• Generic formulations significantly cheaper

1. Slow titration is essential: Cognitive side effects (word-finding difficulty, memory problems) are dose-related and minimised with gradual titration — never rush escalation

1. Weight loss effect — double-edged sword: May benefit patients with obesity-related comorbidities but can be problematic in underweight patients or children; monitor nutritional status

1. Check bicarbonate periodically: Chronic metabolic acidosis may be asymptomatic; particularly important in children, patients on ketogenic diet, or concurrent valproate

1. Counsel on kidney stone prevention: Ensure adequate fluid intake (2–3 litres daily in adults); avoid in patients with recurrent nephrolithiasis unless essential

1. Glaucoma warning: Any sudden visual disturbance or eye pain in first month requires immediate discontinuation and ophthalmology referral — delay may cause permanent vision loss

1. Contraception counselling mandatory: Doses ≥200 mg/day significantly reduce oral contraceptive efficacy; use additional barrier methods or alternative contraception

topiramate; antiepileptic; epilepsy; migraine-prophylaxis; Lennox-Gastaut; cognitive-effects; weight-loss; metabolic-acidosis; nephrolithiasis; teratogenic; NLEM-India; neurology

RxIndia v1.0 — 02 Apr 2025

• CDSCO-approved prescribing information

• Indian Pharmacopoeia

• National Formulary of India (NFI)

• NLEM 2022

• API Textbook of Medicine

• ICMR Guidelines for Epilepsy

• IAP Guidelines for Paediatric Seizure Disorders

• AIIMS Drug Formulary (Neurology/Paediatrics)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• RCTs/meta-analyses (for off-label indications — annotated as off-label)