Schedule H

Oral

• Tablet: 500 mg

• Sachet (powder for oral solution): 500 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Refractory Infantile Spasms (West Syndrome)

First-line for infantile spasms associated with tuberous sclerosis complex; specialist use only

Parameter Recommendation

Starting dose 50 mg/kg/day orally in 2 divided doses

Titration Increase by 25–50 mg/kg/day every 3–4 days based on clinical response

Usual maintenance dose 100–150 mg/kg/day in 2 divided doses

Maximum dose 150 mg/kg/day

Key Clinical Notes:

• Initiation and management by paediatric neurologist only

• Assess response within 2–4 weeks; discontinue if no clinical or EEG improvement

• Particularly effective in infantile spasms due to tuberous sclerosis complex

• Risk of irreversible visual field defects — counsel family before initiation

1. Adjunctive Therapy in Refractory Complex Partial Seizures (Adults)

For drug-resistant focal epilepsy unresponsive to ≥2 standard antiepileptic drugs; specialist use only

Parameter Recommendation

Starting dose 500 mg orally twice daily (1 g/day)

Titration Increase by 500 mg every 3–4 days based on seizure control and tolerability

Usual maintenance dose 1.5–3 g/day in 2 divided doses

Maximum dose 3 g/day

Key Clinical Notes:

• Use only as adjunctive therapy when multiple AEDs have failed

• Not for monotherapy due to risk of irreversible visual field constriction

• Baseline and regular visual field testing mandatory

• Consider discontinuation if inadequate response after 3 months

Secondary Indications — Adults (Off-label)

Not applicable.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Infantile Spasms (West Syndrome)

• Minimum age: 1 month

• Not recommended below 1 month of age

• Not recommended for other paediatric epilepsy syndromes without paediatric neurology supervision

Weight-Based Dosing:

Parameter Recommendation

Starting dose 50 mg/kg/day divided into 2 doses

Titration Increase by 25–50 mg/kg/day every 3–4 days

Usual maintenance dose 100–150 mg/kg/day in 2 divided doses

Maximum dose 150 mg/kg/day

Duration:

• Assess response within 2–4 weeks

• Discontinue if no clinical improvement (cessation of spasms) or EEG improvement (resolution of hypsarrhythmia)

• If effective, continue for shortest duration necessary; reassess need periodically

Safety Monitoring:

• Monitor for sedation, irritability, feeding difficulties

• Visual behaviour monitoring (fixation, tracking) — formal perimetry not feasible in infants

• MRI brain changes (transient signal abnormalities may occur — usually reversible)

• Weigh risk of visual toxicity against benefit of seizure control

Secondary Indications — Paediatric Doses (Off-label)

Not applicable.

Clear Statement: NOT recommended in paediatric patients for generalised epilepsy syndromes, absence seizures, or myoclonic seizures — may worsen these seizure types. Use only for infantile spasms under paediatric neurology supervision.

Creatinine Clearance (mL/min) Recommendation

60 No dose adjustment required

30–60 Reduce dose by 25–33%

10–30 Reduce dose by 50%

<10 or dialysis-dependent Start at 250 mg/day; administer after dialysis sessions; titrate cautiously

Note: Vigabatrin is primarily renally excreted unchanged. Accumulation risk in renal impairment — monitor for CNS toxicity.

Rationale: Vigabatrin undergoes minimal hepatic metabolism.

• Known hypersensitivity to vigabatrin or any excipient

• Pre-existing significant visual field defect or retinal disorder

• History of vigabatrin-induced visual field loss

• Use as monotherapy in any epilepsy syndrome (due to progressive irreversible visual field defects)

• Risk of irreversible bilateral concentric visual field constriction — increases with cumulative dose and duration of therapy

• May exacerbate absence seizures and myoclonic seizures

• Psychiatric disturbances (depression, psychosis, behavioural changes) — more common in patients with psychiatric history

• Infants: Monitor for excessive sedation, irritability, feeding difficulties

• Abrupt withdrawal may precipitate seizures — always taper gradually

• MRI signal changes in infants (usually reversible; clinical significance uncertain)

• Elderly patients: Increased sensitivity to CNS effects

Parameter Details

Safety category Limited human data; animal studies suggest potential harm

When it may be used Only if no safer alternative and benefit clearly outweighs risk; specialist supervision mandatory

Preferred alternatives Lamotrigine or levetiracetam preferred for epilepsy in pregnancy

What to monitor Fetal growth (regular ultrasound); maternal seizure control; consider higher-dose folic acid supplementation (5 mg/day) pre-conception and during first trimester

Parameter Details

Compatibility Excreted in breast milk; use with caution

Expected drug levels in milk Low

Preferred alternatives Lamotrigine or levetiracetam may be considered

What to monitor in infant Sedation, irritability, feeding difficulties, weight gain

• Starting dose: 500 mg once daily

• Titration: Increase slowly every 5–7 days based on tolerability

• Extra risks:

• Increased sensitivity to CNS depression (sedation, confusion, ataxia)

• Higher prevalence of renal impairment — adjust dose accordingly

• Increased risk of psychiatric adverse effects

• Falls risk due to ataxia and sedation

• Maximum dose: Avoid doses exceeding 2 g/day unless clear clinical benefit

• Monitoring: Renal function, cognitive status, gait stability

Interacting Drug(s) Effect Mechanism Management

Phenytoin Vigabatrin reduces phenytoin levels by 20–30% Unknown; possibly altered absorption or distribution Monitor phenytoin levels; increase phenytoin dose if clinically indicated

Note: Vigabatrin does not undergo CYP450-mediated metabolism and has minimal pharmacokinetic drug interactions.

Interacting Drug(s) Effect Management

CNS depressants (benzodiazepines, opioids, sedating antihistamines) Additive sedation Use with caution; monitor for excessive CNS depression

Antipsychotics Additive sedation; may increase extrapyramidal symptoms Monitor closely

Valproate No significant pharmacokinetic interaction; additive CNS effects possible Monitor for sedation

Carbamazepine No significant pharmacokinetic interaction May use concomitantly

Hormonal contraceptives No interaction (vigabatrin is not an enzyme inducer) No dose adjustment required

• Drowsiness, fatigue

• Dizziness

• Headache

• Irritability (especially in children)

• Weight gain

• Tremor

• Ataxia

• Diplopia, blurred vision

• Nausea

• Agitation, excitation (in children)

Adverse Effect Clinical Notes

Irreversible bilateral concentric visual field constriction Affects 30–40% of patients on long-term therapy; may be asymptomatic initially; risk increases with cumulative dose; discontinue if visual symptoms develop; visual field testing mandatory where feasible

MRI signal changes (intramyelinic oedema) Reported mainly in infants; typically reversible on discontinuation; clinical significance uncertain

Psychosis, severe behavioural disturbance May require discontinuation; more common in patients with psychiatric history

Severe depression, suicidal ideation Class effect of antiepileptics; monitor mood closely

Encephalopathy Rare; characterised by marked sedation, stupor; discontinue drug

Anaemia Rare; monitor if symptoms develop

Phase Parameter Frequency

Baseline Visual field testing (Goldman or Humphrey perimetry — in patients ≥8 years who can cooperate); renal function; neurological and psychiatric assessment Before initiation

Infants (<8 years) Visual behaviour monitoring (fixation, tracking, response to peripheral stimuli); parental education on visual signs Each visit

After initiation Seizure response (spasm frequency, EEG if indicated); sedation; behavioural changes Every 2–4 weeks initially

Long-term (adults and older children) Visual field testing Every 6 months

Long-term Renal function (especially in elderly) Every 6–12 months

Long-term Psychiatric assessment; weight; seizure control At each visit

• Sabril (Sanofi) — Tablet, Sachet

• Viganext (Sun Pharma) — Tablet

• Vigatrin (Intas) — Sachet

• Not included in NLEM

• Not under NPPA price control

• Availability may be limited to specialty pharmacy channels

1. Specialist-only drug: All vigabatrin initiations must be referred to paediatric or adult neurology — do not initiate in general practice due to irreversible visual toxicity risk.

1. First-line for tuberous sclerosis-related infantile spasms: Vigabatrin is particularly effective and often the drug of choice when infantile spasms occur in the setting of tuberous sclerosis complex.

1. Time-limited trial: Assess response within 2–4 weeks for infantile spasms; discontinue if no improvement — do not continue ineffective therapy given visual toxicity risk.

1. Visual field monitoring is mandatory: In patients ≥8 years, baseline and 6-monthly perimetry is essential. In infants, formal testing is not feasible — monitor visual behaviour and educate family regarding signs of visual impairment.

1. Avoid in certain seizure types: Vigabatrin may worsen absence seizures, myoclonic seizures, and atonic seizures — confirm seizure type before initiating therapy.

1. Family counselling is essential: Before initiation, families must be informed about the risk of irreversible visual field loss and the importance of monitoring — document informed consent.

vigabatrin; infantile spasms; West syndrome; tuberous sclerosis; refractory epilepsy; visual field defect; GABA inhibitor; paediatric neurology; specialist-only; Schedule H

RxIndia v0.9 — 06 May 2025

• CDSCO product inserts (Sabril, Viganext)

• Indian Pharmacopoeia

• API Textbook of Medicine

• IAP Guidelines (Epilepsy chapter)

• AIIMS Paediatric Neurology protocols (infantile spasms management)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• International RCTs on vigabatrin efficacy in infantile spasms and visual toxicity (supportive only — clearly marked)