Schedule H

Oral

• Tablets (Immediate-Release): 100 mg, 200 mg, 400 mg

• Controlled-Release (CR) Tablets: 200 mg, 400 mg

• Oral Suspension: 100 mg/5 mL

• Chewable Tablets: 100 mg

Note: Injectable formulation is NOT AVAILABLE in India for routine clinical use

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Partial Seizures (with or without secondary generalisation) and Generalised Tonic-Clonic Seizures

Adults — Monotherapy or Adjunctive Therapy:

Parameter Recommendation

Starting dose 100–200 mg twice daily

Titration Increase by 200 mg/day every 3–7 days as tolerated

Usual maintenance dose 800–1200 mg/day in 2–3 divided doses

Maximum dose 1600 mg/day

Clinical Notes:

• Immediate-release formulations require twice or thrice daily dosing

• CR formulations allow twice daily dosing with fewer peak-related adverse effects

• Avoid abrupt withdrawal — taper gradually over 2–6 months

• Therapeutic drug monitoring: target trough level 4–12 mcg/mL

• Not effective for absence seizures — may worsen them

1. Trigeminal Neuralgia

Adults — First-line Pharmacotherapy:

Parameter Recommendation

Starting dose 100 mg twice daily

Titration Increase by 100–200 mg every 2–3 days based on pain response

Usual maintenance dose 400–800 mg/day in 2–3 divided doses

Maximum dose 1200 mg/day

Clinical Notes:

• Use lowest effective dose to maintain remission

• Periodic dose reduction attempts recommended to assess ongoing requirement

• CR formulations preferred for sustained analgesia

• Response typically seen within first week

1. Bipolar Affective Disorder — Acute Mania and Maintenance

Adults — Under Psychiatrist Supervision:

Parameter Recommendation

Starting dose 200 mg twice daily

Titration Increase by 200 mg every 3–5 days based on response and tolerability

Usual maintenance dose 600–1000 mg/day in divided doses

Maximum dose 1600 mg/day (specialist supervision required)

Clinical Notes:

• Second-line agent after lithium and valproate in Indian psychiatric practice

• CR formulations preferred to minimise peak-related CNS effects

• Serum level monitoring helpful in non-responders

• Monitor for drug interactions with other psychotropics

Secondary Indications – Adults Only (Off-label)

Indication Dose Duration Supervision Evidence Basis

Diabetic Peripheral Neuropathy — OFF-LABEL Starting: 100 mg BD; Maintenance: 400–800 mg/day 4–12 weeks trial Specialist only Indian pain medicine practice; supportive clinical experience

Restless Leg Syndrome — OFF-LABEL Starting: 100 mg at bedtime; Max: 400 mg/night Short-term/intermittent Specialist only Limited RCT data; Indian neurology practice

Glossopharyngeal Neuralgia — OFF-LABEL As per trigeminal neuralgia dosing As required Specialist only Clinical experience; extrapolated from trigeminal neuralgia

PAEDIATRIC DOSING (Specialist Only)

Primary Indications: Partial Seizures, Generalised Tonic-Clonic Seizures

Age Restriction: Not recommended below 1 month of age except under specialist paediatric neurology supervision.

1–6 months 5 mg/kg/day in 2–3 divided doses Increase by 5 mg/kg/week 10–20 mg/kg/day 20 mg/kg/day

6 months – 1 year 5–10 mg/kg/day in 2–3 divided doses Increase by 5 mg/kg every 5–7 days 10–20 mg/kg/day 35 mg/kg/day

1–5 years 10 mg/kg/day in 2–3 divided doses Increase by 5 mg/kg every 5–7 days 15–25 mg/kg/day 35 mg/kg/day

6–12 years 10 mg/kg/day OR 100–200 mg/day Increase by 100 mg every 3–5 days 20–30 mg/kg/day OR 400–800 mg/day 35 mg/kg/day OR 1000 mg/day

12 years 100–200 mg twice daily Increase by 200 mg every 3–5 days 800–1200 mg/day 1600 mg/day

Safety Monitoring:

• Baseline and periodic CBC with differential count

• LFTs at baseline and during first 3 months

• Serum sodium monitoring (risk of SIADH)

• Therapeutic drug monitoring if seizure control inadequate

• CR formulations preferred in older children for better compliance

Secondary Indications – Paediatric (Off-label)

Indication Notes

Trigeminal Neuralgia (rare in children) — OFF-LABEL Dose as per weight-based seizure guidelines; specialist only

Paediatric Bipolar Disorder — OFF-LABEL Child psychiatrist supervision mandatory; adolescent dosing applies; monitor for behavioural effects

• Known hypersensitivity to carbamazepine, oxcarbazepine, or tricyclic antidepressants

• History of bone marrow depression or blood dyscrasias

• Acute intermittent porphyria

• Concomitant or recent (within 14 days) MAO inhibitor therapy

• Known HLA-B*1502 positivity (high risk of SJS/TEN) — screening recommended in at-risk populations

• Atrioventricular conduction block (second or third degree)

• Severe hepatic impairment

• Concomitant use with voriconazole (loss of antifungal efficacy)

• History of hepatic disease or alcoholism — enhanced hepatotoxicity risk

• Pre-existing hyponatraemia or conditions predisposing to SIADH

• Cardiac disease, especially arrhythmias or heart failure

• History of haematological reactions to other drugs

• Mixed seizure disorders including absence seizures — may exacerbate absences

• Elderly patients — increased sensitivity to CNS effects

• History of psychosis or behavioural disturbance

• Risk of suicidal ideation — monitor mood and behaviour

• Patients of Asian ancestry (Han Chinese, Thai, Indian populations from certain regions) — increased HLA-B*1502 prevalence

• Glaucoma — mild anticholinergic effects

Parameter Details

Risk category Known teratogen; associated with neural tube defects, craniofacial abnormalities, developmental delay

Preferred alternatives Lamotrigine, levetiracetam — preferred for epilepsy management during pregnancy

When may be used Only if seizure control cannot be achieved with safer alternatives; monotherapy at lowest effective dose preferred

Monitoring required High-dose folic acid (5 mg/day) from preconception through first trimester; targeted anomaly scan at 18–20 weeks; maternal serum AFP; serial fetal growth monitoring

Neonatal concerns Monitor neonate for withdrawal symptoms and vitamin K deficiency bleeding

Parameter Details

Compatibility Generally compatible with breastfeeding; benefits usually outweigh risks

Drug levels in milk Moderate (infant receives approximately 5–10% of maternal weight-adjusted dose)

Preferred alternatives Lamotrigine, levetiracetam also compatible; valproate carries higher concerns

Infant monitoring Observe for sedation, poor feeding, jaundice, hepatic dysfunction; monitor infant weight gain

Parameter Recommendation

Starting dose 100 mg once or twice daily

Titration Very gradual — increase by 100 mg every 5–7 days

Special risks Increased CNS depression, ataxia, falls, confusion; hyponatraemia more common; cardiac conduction effects; drug interactions with polypharmacy

Monitoring Serum sodium at baseline and periodically; gait assessment; cognitive monitoring

Drug/Class Mechanism/Effect Recommendation

MAO inhibitors Serotonergic crisis risk; unpredictable toxicity Contraindicated — 14-day washout required

Voriconazole Carbamazepine induces metabolism → subtherapeutic antifungal levels Contraindicated — avoid combination

Clarithromycin, erythromycin Strong CYP3A4 inhibition → carbamazepine toxicity Avoid if possible; if unavoidable, reduce carbamazepine dose and monitor levels

Valproate Increases carbamazepine-10,11-epoxide (active/toxic metabolite) Monitor for toxicity even with "normal" carbamazepine levels

Phenytoin, phenobarbital Mutual enzyme induction → reduced efficacy of both Monitor levels of both drugs; dose adjustment often needed

Warfarin CYP induction → reduced warfarin effect → decreased INR Monitor INR closely; warfarin dose increase often required

Combined oral contraceptives Reduced contraceptive efficacy Advise alternative or additional contraception

Doxycycline Reduced doxycycline half-life and efficacy Consider alternative antibiotic or higher doxycycline dose

Drug/Class Effect Recommendation

Isoniazid Inhibits carbamazepine metabolism; additive hepatotoxicity Monitor LFTs frequently; watch for carbamazepine toxicity

Diltiazem, verapamil Moderate CYP3A4 inhibition → raised carbamazepine levels Monitor for toxicity; may need dose reduction

Fluoxetine, fluvoxamine CYP inhibition → raised carbamazepine levels Monitor for CNS toxicity; consider dose adjustment

Cimetidine Inhibits carbamazepine metabolism Prefer ranitidine or PPIs; monitor if used together

Theophylline Induced metabolism → reduced theophylline levels Monitor theophylline levels; dose increase may be needed

Lithium Increased risk of neurotoxicity without changing lithium levels Monitor for tremor, ataxia, confusion; use cautiously

Rifampicin Enzyme induction → reduced carbamazepine efficacy Monitor seizure control; may need dose increase

Methadone Induced metabolism → reduced methadone effect Monitor for opioid withdrawal; methadone dose increase may be needed

• Dizziness and ataxia (especially during initiation and dose increases)

• Nausea and vomiting

• Diplopia and blurred vision

• Drowsiness and fatigue

• Headache

• Dry mouth

• Mild leucopenia (often transient and benign)

• Mild transaminase elevation

• Skin rash (non-serious; discontinue if concerning features)

• Hyponatraemia (SIADH)

Adverse Effect Clinical Action

Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis Immediate discontinuation and hospitalisation — especially in HLA-B*1502 positive patients

Aplastic anaemia / Agranulocytosis Discontinue immediately; urgent haematology referral

DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) Discontinue; supportive care; may require corticosteroids

Hepatic failure Discontinue; liver function monitoring; specialist referral

Cardiac arrhythmias / AV block ECG monitoring; discontinue if significant conduction abnormalities

Severe hyponatraemia May require fluid restriction; discontinuation if severe or symptomatic

Suicidal ideation / behavioural changes Close psychiatric monitoring; consider drug discontinuation

Pancreatitis Discontinue; supportive management

Multi-organ hypersensitivity Immediate discontinuation; hospitalisation

Baseline:

• Complete blood count with differential

• Liver function tests (AST, ALT, ALP, bilirubin)

• Renal function (serum creatinine, electrolytes)

• Serum sodium

• HLA-B*1502 screening in high-risk populations (North-East India, patients of Han Chinese/Thai ancestry)

• ECG in patients with cardiac history or elderly

• Pregnancy test in women of childbearing age

After Initiation / Dose Change:

• Serum carbamazepine level after steady state achieved (5–7 days)

• CBC and LFTs at 2 weeks, 4 weeks, then 3 months

• Serum sodium at 2–4 weeks

• Clinical assessment for rash, CNS effects

Long-term Monitoring:

• CBC and LFTs every 6–12 months

• Serum sodium every 3–6 months (more frequently in elderly)

• Annual thyroid function tests

• Bone health assessment with long-term use (vitamin D, calcium, DEXA if indicated)

• Seizure diary review

• Psychiatric assessment for mood and behaviour

Immediate-Release Tablets:

• Tegretol (Novartis)

• Zeptol (Sun Pharma)

• Mazetol (Intas)

• Carbatol (Sanofi)

• Zen (Mankind)

• Carzep (Cipla)

Controlled-Release Tablets:

• Tegretol CR (Novartis)

• Zeptol CR (Sun Pharma)

• Mazetol CR (Intas)

Oral Suspension:

• Tegretol Suspension (Novartis)

• Zeptol Syrup (Sun Pharma)

Chewable Tablets:

• Tegretol Chewable (Novartis)

• Included in NLEM 2022 for epilepsy

• NPPA price ceiling applicable for scheduled formulations

• Generic options widely available at lower cost

1. Slow titration is essential — most CNS and GI adverse effects are dose-related and occur during initiation; gradual uptitration improves tolerability significantly

1. HLA-B*1502 testing before initiation — strongly recommended in patients from North-East India and those of Han Chinese, Thai, or South-East Asian ancestry to identify high-risk individuals for SJS/TEN

1. Brand consistency matters — bioavailability varies between manufacturers; avoid switching brands once seizure control achieved; if switch necessary, monitor closely

1. Avoid in absence and myoclonic seizures — carbamazepine may worsen these seizure types; contraindicated in juvenile myoclonic epilepsy

1. Autoinduction phenomenon — carbamazepine induces its own metabolism over 2–4 weeks; initial dose may need upward adjustment after this period to maintain therapeutic levels

1. Hyponatraemia in elderly — carbamazepine-induced SIADH is common in patients over 65 years; routine sodium monitoring essential

1. Contraceptive counselling mandatory — enzyme induction significantly reduces efficacy of hormonal contraceptives; advise barrier methods or IUD

anticonvulsant; epilepsy; partial seizures; trigeminal neuralgia; bipolar disorder; mood stabiliser; HLA-B*1502; SJS-risk; CYP3A4-inducer; hyponatraemia; NLEM India; Schedule H; teratogenic

RxIndia v1.0 — 05 Jun 2025

• CDSCO approved product inserts

• Indian Pharmacopoeia

• National List of Essential Medicines (NLEM) 2022

• API Textbook of Medicine

• AIIMS Treatment Guidelines — Epilepsy Management

• ICMR Guidelines on Epilepsy

• IAP Paediatric Drug Formulary

• Indian Psychiatric Society treatment protocols

• Indian Epilepsy Society recommendations

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (supportive)