Schedule H1

Oral

• Perampanel 2 mg film-coated tablet

• Perampanel 4 mg film-coated tablet

• Perampanel 6 mg film-coated tablet

• Perampanel 8 mg film-coated tablet

• Perampanel 10 mg film-coated tablet

• Perampanel 12 mg film-coated tablet

• Oral suspension: NOT AVAILABLE in India

• Injectable formulation: NOT AVAILABLE in India

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Focal-Onset Seizures (with or without secondary generalisation) — Adults and Adolescents ≥12 years

As adjunctive therapy

Parameter Recommendation

Starting dose 2 mg orally once daily at bedtime

Titration Increase by 2 mg increments at intervals of at least 1 week (slower titration preferred to minimise neuropsychiatric adverse effects)

Usual maintenance dose 4–8 mg once daily at bedtime

Maximum dose 12 mg once daily

Clinical Notes:

• Administer at bedtime consistently to reduce daytime sedation

• Patients on enzyme-inducing AEDs (Carbamazepine, Phenytoin, Oxcarbazepine) may require higher doses due to reduced Perampanel plasma levels

• Very long half-life (~105 hours); steady-state achieved after 2–3 weeks

• Gradual tapering required when discontinuing to avoid rebound seizures

1. Primary Generalised Tonic-Clonic Seizures — Adults and Adolescents ≥12 years

As adjunctive therapy in idiopathic generalised epilepsy

Parameter Recommendation

Starting dose 2 mg orally once daily at bedtime

Titration Increase by 2 mg increments at weekly intervals based on response and tolerability

Usual maintenance dose 4–8 mg once daily at bedtime

Maximum dose 12 mg once daily

Clinical Notes:

• Same enzyme-inducer considerations apply

• Monitor for psychiatric adverse effects during titration

• Once-daily bedtime dosing improves adherence

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

Indication Dose Duration Notes

Refractory status epilepticus (adjunctive) 8–12 mg once daily (via nasogastric tube if needed) Based on seizure control OFF-LABEL; Specialist only; Based on case series and tertiary epilepsy centre practice in India

Lennox-Gastaut Syndrome (adjunctive) Start 2 mg daily; titrate slowly to 4–8 mg daily Long-term OFF-LABEL; Specialist only; Based on international RCTs and use by paediatric neurologists in India for drug-resistant epilepsy

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Focal-Onset Seizures and Primary Generalised Tonic-Clonic Seizures — Adolescents ≥12 years

Parameter Recommendation

Starting dose 2 mg orally once daily at bedtime

Titration Increase by 2 mg increments at weekly intervals

Usual maintenance dose 4–8 mg once daily

Maximum dose 12 mg once daily

Clinical Notes:

• Same as adult dosing for adolescents ≥12 years

• Close monitoring for behavioural changes (aggression, irritability) essential in adolescents

Secondary Indications — Paediatric doses (Off-label, if any)

Children 4–11 years (Off-label use in India)

Body Weight Starting Dose Titration Usual Maintenance Maximum Dose

<20 kg 0.015 mg/kg once daily at bedtime Increase by 0.015 mg/kg every 1–2 weeks 0.05–0.15 mg/kg once daily 0.18 mg/kg/day (max 8 mg/day)

20–30 kg 1–2 mg once daily Increase by 1 mg every 1–2 weeks 2–4 mg once daily 6 mg once daily

30 kg 2 mg once daily Increase by 2 mg every 1–2 weeks 4–8 mg once daily 8–12 mg once daily

Indications (Off-label):

• Focal-onset seizures

• Lennox-Gastaut Syndrome (adjunctive)

Notes:

• OFF-LABEL below 12 years in India

• Specialist paediatric neurology supervision mandatory

• Based on international paediatric RCT data and Indian tertiary epilepsy centre practice

Safety Monitoring:

• Behavioural changes: aggression, irritability, mood swings

• Sleep disturbances

• Sedation and dizziness

• Seizure frequency documentation

• Academic performance and cognitive function

Statement: Not recommended in children below 4 years of age. Use in children 4–11 years only under specialist paediatric neurology supervision with documented informed consent.

Severe impairment (eGFR <30) Use with caution; limited data; avoid if possible

Haemodialysis Avoid use — Perampanel is highly protein-bound (95–96%) and not dialysable

Peritoneal dialysis No data; avoid if possible

Note: Perampanel is extensively hepatically metabolised via CYP3A4; exposure significantly increased in hepatic impairment.

• Known hypersensitivity to Perampanel or any excipient in the formulation

• Severe hepatic impairment (Child-Pugh C)

• History of serious psychiatric adverse reactions to Perampanel (severe aggression, psychosis, homicidal ideation)

• Psychiatric history: Pre-existing depression, anxiety, psychosis, or history of suicidal ideation — Perampanel may exacerbate; close monitoring essential

• Behavioural effects: Aggression, hostility, and irritability reported even at low doses; more common in adolescents

• Alcohol use: Additive CNS depression and enhanced aggression risk; advise strict avoidance or significant limitation

• Elderly patients: Increased risk of falls, sedation, and confusion

• Concurrent CNS depressants: Additive sedation effects

• Enzyme-inducing AEDs: Reduced Perampanel efficacy; may need higher doses

• Driving and machinery operation: Counsel regarding sedation and dizziness risk

• Abrupt discontinuation: Risk of rebound seizures or status epilepticus — always taper gradually

Parameter Details

Overall safety Limited human data; animal studies show developmental toxicity; avoid unless no alternatives

Recommendation Not recommended during pregnancy; use only if potential benefit clearly outweighs fetal risk

Preferred alternatives Levetiracetam, Lamotrigine (more pregnancy safety data available in Indian obstetric practice)

If used (specialist only) Use lowest effective dose; monotherapy preferred; ensure adequate folate supplementation (5 mg/day)

Monitoring Seizure control; fetal growth surveillance via ultrasound; structural anomaly screening

Note: Counsel women of childbearing potential regarding effective contraception. Perampanel at doses ≥8 mg/day may reduce efficacy of levonorgestrel-containing contraceptives.

Parameter Details

Compatibility Limited human data; likely compatible based on pharmacokinetic profile

Excretion in milk Unknown; expected low to moderate based on high protein binding

Preferred alternatives Levetiracetam (more lactation safety data available)

Recommendation May be used with caution during breastfeeding if clinically indicated; monitor infant

Infant monitoring Sedation, irritability, poor feeding, weight gain

Parameter Recommendation

Starting dose 2 mg once daily at bedtime (some clinicians prefer 1 mg if available as split dose for very frail patients)

Titration Slow titration essential (every 2–4 weeks); assess tolerance carefully

Special considerations Age-related hepatic decline may increase drug exposure

Additional risks Falls risk (sedation, dizziness, ataxia); cognitive impairment; confusion; polypharmacy interactions

Interacting Drug Effect Management

Carbamazepine ↓ Perampanel levels by ~67% (strong CYP3A4 induction) Higher Perampanel doses likely needed (up to 12 mg/day); monitor seizure control

Phenytoin ↓ Perampanel levels by ~50% (CYP3A4 induction) Higher Perampanel doses may be required; monitor seizure control

Oxcarbazepine ↓ Perampanel levels (CYP3A4 induction) Consider dose increase; monitor response

Rifampicin ↓ Perampanel levels significantly (potent CYP3A4 inducer) Avoid combination if possible; if unavoidable, significant dose increase likely needed

Alcohol Additive CNS depression; enhanced aggression reported Advise strict avoidance or significant limitation

CNS depressants (Benzodiazepines, Opioids, Sedative-hypnotics) Additive sedation and respiratory depression Use with caution; monitor closely; counsel patient

Levonorgestrel-containing contraceptives ↓ Contraceptive efficacy at Perampanel doses ≥8 mg/day Advise additional or alternative contraceptive methods

Interacting Drug Effect Management

Ketoconazole, Itraconazole ↑ Perampanel levels (CYP3A4 inhibition) Monitor for increased adverse effects; may need dose reduction

Clarithromycin, Erythromycin Potential ↑ Perampanel levels (CYP3A4 inhibition) Monitor for increased sedation and adverse effects

Clobazam Enhanced sedation Monitor for excessive drowsiness

Valproate No significant pharmacokinetic interaction Safe to combine; routine monitoring

Lamotrigine No significant interaction Safe to combine

Levetiracetam No significant interaction Safe to combine

Topiramate Minor reduction in Perampanel levels Usually no dose adjustment needed

Phenobarbital, Primidone ↓ Perampanel levels (enzyme induction) May need higher Perampanel doses

• Dizziness (dose-related; very common)

• Somnolence / drowsiness

• Headache

• Fatigue

• Irritability

• Ataxia / gait disturbance

• Nausea

• Weight gain

• Vertigo

• Blurred vision

• Dysarthria

Adverse Effect Notes

Suicidal ideation / behaviour Class effect of antiepileptics; monitor psychiatric status; requires immediate evaluation and possible discontinuation

Aggression / hostility / homicidal ideation May occur even at low doses; more common in adolescents; may require dose reduction or discontinuation

Psychosis / mania / paranoia In predisposed patients; requires specialist psychiatric evaluation

Falls and injuries Especially in elderly due to dizziness and ataxia

Serious skin reactions (SJS/TEN) Rare; discontinue immediately if suspected

Status epilepticus Risk with abrupt discontinuation — always taper gradually

During titration (weekly to monthly) Behavioural assessment (aggression, mood changes, suicidal thoughts); sedation and dizziness; seizure frequency

Long-term (every 3–6 months) Seizure control; periodic LFTs if hepatic impairment; psychiatric status; medication adherence; weight monitoring

Special situations Serum levels of co-administered AEDs if clinically relevant (e.g., Phenytoin levels if toxicity suspected)

• Fycompa® (Eisai) — Innovator brand

• Peratag® (Zydus Cadila)

• Persam® (Emcure)

• Pepeca® (Micro Labs)

• Perampan® (Sun Pharma)

Note: Not listed under NLEM; prices not NPPA-controlled. Significant price variation across brands and regions. High-cost AED.

1. Slow titration is key: Most psychiatric adverse effects (aggression, irritability) occur during rapid titration. Increase by 2 mg weekly at minimum; slower titration (every 2 weeks) reduces dropout rates.

1. Bedtime dosing essential: Very long half-life (~105 hours) allows once-daily dosing. Administer at bedtime consistently to minimise daytime sedation and dizziness.

1. Enzyme-inducer awareness: Patients on Carbamazepine, Phenytoin, or Oxcarbazepine may need Perampanel doses up to 12 mg/day. When withdrawing enzyme inducers, reduce Perampanel dose to avoid toxicity.

1. Adolescent psychiatric monitoring: Aggression and hostility more common in younger patients. Counsel families to report behavioural changes immediately.

1. Contraceptive counselling mandatory: At doses ≥8 mg/day, levonorgestrel-containing contraceptive efficacy may be reduced. Advise additional or alternative contraception.

1. Unique mechanism: Only approved AMPA receptor antagonist; consider when other mechanisms (sodium channel blockers, SV2A ligands) have failed or are not tolerated.

perampanel; Fycompa; antiepileptic; focal seizures; PGTCS; AMPA antagonist; adjunctive AED; psychiatric-risk; bedtime-dosing; Schedule H1; enzyme-inducer interaction; neurology

RxIndia v1.0 — 01 Jun 2025

• CDSCO approved product information

• Indian Pharmacopoeia

• National Formulary of India (NFI)

• API Textbook of Medicine

• Harrison's Principles of Internal Medicine (21st edition)

• Goodman & Gilman's Pharmacological Basis of Therapeutics

• AIIMS Epilepsy treatment protocols

• Indian Epilepsy Society clinical practice recommendations

• International RCTs for paediatric off-label use (supportive reference — clearly marked)