Schedule H

Oral

• Tablet: 400 mg

• Tablet: 600 mg

• Oral Suspension: NOT AVAILABLE in India

• Injectable form: NOT AVAILABLE in India

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Lennox-Gastaut Syndrome (Adjunctive therapy in refractory cases)

Parameter Recommendation

Starting dose 15 mg/kg/day divided into 3–4 doses

Titration Increase by 5–10 mg/kg/day every week

Usual maintenance dose 30–45 mg/kg/day in divided doses

Maximum dose 60 mg/kg/day

Key clinical notes:

• Reserved exclusively for patients who have failed multiple other antiepileptic agents

• Mandatory informed consent regarding risk of aplastic anaemia and hepatic failure before initiation

• Initiate and supervise only under specialist neurologist care

1. Partial Onset Seizures (Adjunctive therapy in refractory epilepsy — Adults)

Parameter Recommendation

Starting dose 1,200 mg/day in 3–4 divided doses

Titration Increase by 600 mg/day weekly as tolerated

Usual maintenance dose 2,400–3,600 mg/day

Maximum dose 3,600 mg/day

Key clinical notes:

• Indicated only when other AEDs have been inadequate

• Close haematologic and hepatic monitoring essential throughout treatment

• Consider reducing concomitant AED doses by 20–33% when adding felbamate to minimise toxicity

Secondary Indications – Adults (Off-label, if any)

Not applicable — No established off-label indications for routine clinical use in India. Use is strictly restricted to refractory epilepsy under specialist supervision.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Lennox-Gastaut Syndrome — Adjunctive therapy (Age ≥2 years)

2–14 years 15 mg/kg/day in 3–4 divided doses Increase by 5–10 mg/kg/day every 1 week 30–45 mg/kg/day 60 mg/kg/day

Safety notes:

• Minimum age for initiation: 2 years

• Must be managed under paediatric neurologist supervision only

• Titrate cautiously with regular CBC and LFT monitoring

• High vigilance required for early signs of bone marrow suppression or hepatotoxicity

• Obtain written informed consent from parents/guardians before starting therapy

Secondary Indications – Paediatrics (Off-label, if any)

Not applicable — Use outside Lennox-Gastaut Syndrome is not recommended in paediatric population due to significant safety concerns.

Statement: Not recommended in children below 2 years of age under any circumstances.

• Known hypersensitivity to felbamate or any component of formulation

• History of aplastic anaemia or any bone marrow depression disorder

• Pre-existing hepatic dysfunction or history of hepatic failure

• Blood dyscrasias of any aetiology

• Concurrent use with highly hepatotoxic agents (unless initiated by specialist with close monitoring)

• Complete blood count and liver function tests must be performed before and during therapy

• Discontinue immediately upon any sign of bone marrow suppression (unexplained bruising, bleeding, pallor, fever, infection)

• Discontinue immediately if hepatitis symptoms appear (jaundice, dark urine, right upper quadrant pain, anorexia)

• Monitor nutritional status — risk of significant anorexia and weight loss

• Prescribe only under supervision of a neurologist experienced in managing refractory epilepsy

• Warn patients to report any new symptoms promptly

Aspect Recommendation

Overall safety Limited human data; use only if no safer alternative exists

Risk period Avoid during first trimester if possible

Preferred alternatives Levetiracetam, Lamotrigine (as per Indian obstetric neurology practice)

When may be used Only if seizures are uncontrolled on safer agents and benefits clearly outweigh risks

Monitoring required Serial fetal growth scans; maternal LFTs every 2–4 weeks; CBC monitoring

Aspect Recommendation

Compatibility Not recommended during breastfeeding

Drug transfer to milk Expected to pass into breast milk; quantitative data limited

Preferred alternatives Levetiracetam, Lamotrigine (if compatible with seizure control)

Infant monitoring (if used) Observe for drowsiness, poor feeding, irritability, inadequate weight gain

• Starting dose: Begin at lower end of adult dosing range

• Titration: Slower increments (every 2 weeks instead of weekly)

• Specific risks:

• Reduced hepatic and renal reserve increases toxicity risk

• Higher incidence of CNS adverse effects (sedation, confusion, ataxia)

• Increased risk of falls and gait instability

• Monitoring: More frequent LFT and CBC checks; watch for cognitive changes

Interacting Drug Effect Clinical Action

Phenytoin Felbamate increases phenytoin levels significantly Reduce phenytoin dose by 20–40%; monitor phenytoin levels

Valproate Valproate increases felbamate levels; additive hepatotoxicity risk Reduce valproate dose; monitor LFTs closely

Carbamazepine Carbamazepine induces felbamate metabolism (via CYP3A4) May need higher felbamate dose; reduce carbamazepine-epoxide toxicity by dose adjustment

Alcohol / CNS depressants Additive CNS depression Avoid concurrent use

Interacting Drug Effect Clinical Action

Phenobarbital May decrease felbamate levels via enzyme induction Monitor seizure control; may need felbamate dose adjustment

Oral contraceptives Felbamate induces hepatic metabolism Reduced contraceptive efficacy; advise additional contraception

Lamotrigine Additive CNS effects possible Monitor for excessive sedation; consider lamotrigine dose reduction

Warfarin Minor interaction possible (CYP2C9 effect) Monitor INR more frequently if coadministered

Rifampicin Strong enzyme inducer; may reduce felbamate efficacy Avoid if possible; adjust felbamate dose if used

• Anorexia and weight loss

• Nausea and vomiting

• Headache

• Insomnia

• Dizziness

• Ataxia

• Diplopia

• Irritability and mood changes

• Somnolence

Adverse Effect Action Required

Aplastic anaemia Rare but potentially fatal; requires immediate permanent discontinuation and haematology referral

Acute hepatic failure Can develop rapidly; requires immediate withdrawal and hospitalisation

Stevens-Johnson syndrome / TEN Rare; discontinue immediately; supportive care in burns/ICU setting

Suicidal ideation/behaviour Warn patients; monitor closely; psychiatric consultation if needed

Baseline (before initiation):

• Complete blood count with differential (especially WBC, platelets)

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

• Renal function (serum creatinine, eGFR)

After initiation:

• CBC and LFT at 2 weeks

• Then every 1–2 weeks for first 6 months of therapy

Long-term:

• CBC and LFT every 1–3 months

• Monitor weight and nutritional status regularly

• Screen for mood changes and suicidal ideation at each visit

• FELBAM-400 / FELBAM-600 (Intas Pharmaceuticals)

• FELMINA 400 / 600 (Sun Pharma)

• FEBALATE (Micro Labs)

Note: Not included under NLEM; cost may be a barrier for long-term use in some patients.

• Felbamate should never be considered first-line therapy; reserve strictly for treatment-resistant Lennox-Gastaut syndrome or partial seizures unresponsive to multiple AEDs

• Obtain and document written informed consent regarding risks of aplastic anaemia and hepatic failure before initiation

• Missing scheduled CBC/LFT monitoring increases both clinical and medicolegal risk substantially

• When adding felbamate to existing AED regimen, proactively reduce doses of phenytoin (by 20–40%) and valproate (by 30–50%) to prevent toxicity

• Educate patients and caregivers about warning signs requiring immediate medical attention: unusual bruising, bleeding, persistent fever, yellowing of eyes/skin, dark urine

• Even mild elevation in LFTs warrants repeat testing within 1 week and dose reassessment

felbamate; epilepsy; Lennox-Gastaut syndrome; partial seizures; refractory epilepsy; aplastic anaemia; hepatotoxicity; antiepileptic; Schedule-H; paediatric neurology; specialist-only

RxIndia v1.0 — 24 Mar 2025

• CDSCO Product Listing

• Indian Pharmacopoeia / National Formulary of India 2021

• AIIMS Paediatric Neurology Protocols

• API Textbook of Medicine

• Indian Epilepsy Society Recommendations

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (for off-label paediatric evidence support)

• Published RCTs on felbamate efficacy in Lennox-Gastaut syndrome (evidence basis for refractory cases)