Schedule H

Oral, Intravenous

• Brivaracetam 25 mg tablet

• Brivaracetam 50 mg tablet

• Brivaracetam 75 mg tablet

• Brivaracetam 100 mg tablet

• Brivaracetam oral solution 10 mg/mL

• Brivaracetam injection 10 mg/mL (50 mg/5 mL vial)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Focal (Partial-Onset) Seizures — Adults and Adolescents ≥16 years

As monotherapy or adjunctive therapy for focal seizures with or without secondary generalisation

Oral Administration:

Parameter Recommendation

Starting dose 50 mg orally twice daily (100 mg/day)

Titration May adjust based on clinical response; can start at 25 mg twice daily if tolerability concerns

Usual maintenance dose 50–100 mg twice daily (100–200 mg/day)

Maximum dose 200 mg/day (100 mg twice daily)

Intravenous Administration:

When oral route temporarily not feasible

Parameter Recommendation

Starting dose 50 mg IV twice daily (equivalent to oral dose)

Titration Same as oral

Usual maintenance dose 50–100 mg IV twice daily

Maximum dose 200 mg/day

Clinical Notes:

• IV infusion: Administer over 2–15 minutes; may be given as bolus or diluted in compatible IV fluid (NS, D5W, or Ringer's Lactate)

• Transition from IV to oral as soon as feasible (bioequivalent doses)

• No loading dose required for routine initiation

• Taper gradually when discontinuing (reduce dose weekly) to avoid rebound seizures

• Can be administered without regard to food

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

Indication Dose Duration Notes

Primary generalised tonic-clonic seizures 50–100 mg twice daily As per seizure control OFF-LABEL; Specialist only; Limited RCT data; Used at Indian tertiary epilepsy centres when first-line agents inadequate

Myoclonic seizures (adjunctive) 50 mg twice daily, titrate to 100 mg twice daily Variable OFF-LABEL; Specialist only; Based on mechanism similarity to Levetiracetam; Limited evidence

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Focal (Partial-Onset) Seizures — Children ≥4 years

As adjunctive therapy

Weight-Based Dosing Table:

Body Weight Starting Dose Titration Usual Maintenance Dose Maximum Dose

11–20 kg 0.5 mg/kg twice daily Increase by 0.5 mg/kg/dose every 1–2 weeks 1–2 mg/kg twice daily 2.5 mg/kg twice daily (max 50 mg twice daily)

21–50 kg 0.5 mg/kg twice daily Increase by 0.5 mg/kg/dose every 1–2 weeks 1–2 mg/kg twice daily 2 mg/kg twice daily (max 100 mg twice daily)

50 kg 25–50 mg twice daily Increase by 25 mg/dose every 1–2 weeks 50–100 mg twice daily 100 mg twice daily

Clinical Notes:

• Oral solution (10 mg/mL) preferred for accurate weight-based dosing in younger children

• Measure oral solution using calibrated measuring device

• Same gradual tapering advised when discontinuing

Safety Monitoring:

• Behavioural changes (irritability, aggression, mood disturbance)

• Sedation and somnolence

• Seizure frequency documentation

• Growth parameters at regular intervals

Minimum Age: Not recommended below 4 years of age. Use only under paediatric neurology specialist supervision.

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

Indication Dose Duration Notes

Generalised epilepsy syndromes (e.g., Lennox-Gastaut syndrome) 1–2 mg/kg/day in 2 divided doses; titrate based on response Variable; long-term OFF-LABEL; Specialist only; Limited to refractory epilepsy centres; Based on international case series

Statement: Not recommended in children below 4 years except under specialist paediatric neurology supervision with documented risk-benefit assessment.

Severe impairment (eGFR <30) Use with caution; no specific dose reduction recommended but monitor closely

Haemodialysis Not significantly dialysed; no supplemental dose needed post-dialysis

Peritoneal dialysis No data; use with caution

Note: Brivaracetam exposure increased in hepatic impairment; dose reduction of approximately one-third recommended across all severities.

• Known hypersensitivity to Brivaracetam or any excipient in the formulation

• History of hypersensitivity reaction to Levetiracetam (structural analogue — cross-reactivity possible)

• Psychiatric disorders: History of depression, anxiety, psychosis, or suicidal ideation — Brivaracetam may exacerbate; monitor closely during initiation

• Behavioural effects: Aggression, irritability, and mood changes reported; lower incidence than Levetiracetam but still possible

• Abrupt discontinuation: Risk of increased seizure frequency or status epilepticus — always taper gradually

• Hepatic impairment: Reduced clearance; dose adjustment needed

• Concurrent CNS depressants: Additive sedation; counsel regarding driving and operating machinery

• Elderly: Increased susceptibility to CNS adverse effects

Parameter Details

Overall safety Limited human data; animal studies show developmental toxicity at high doses

Recommendation Use only if potential benefit justifies risk; specialist input required

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

If used Use lowest effective dose; monotherapy preferred

Monitoring Seizure control, fetal growth via ultrasound, folate supplementation (5 mg/day) recommended

Note: Enrol patients in pregnancy registries where available for pharmacovigilance.

Parameter Details

Compatibility Likely compatible based on pharmacological profile and structural similarity to Levetiracetam

Excretion in milk Expected low to moderate (extrapolated from Levetiracetam data)

Preferred alternatives Levetiracetam (more lactation data available)

Recommendation May be used with caution during breastfeeding if clinically indicated

Infant monitoring Sedation, poor feeding, irritability, weight gain

Parameter Recommendation

Starting dose 25 mg twice daily (lower end of dosing range)

Titration Slower titration advisable (every 2–4 weeks)

Special considerations Age-related decline in renal/hepatic function may affect clearance

Additional risks Falls risk due to dizziness and somnolence; cognitive effects; polypharmacy considerations

Interacting Drug Effect Management

Rifampicin ↓ Brivaracetam levels by ~45% (strong CYP2C19 inducer) Consider increasing Brivaracetam dose; monitor seizure control

Levetiracetam Same mechanism (SV2A binding); no additive efficacy, potential for increased adverse effects Avoid concurrent use — switch from one to other, do not combine

Alcohol Additive CNS depression Advise avoidance or significant reduction in alcohol intake

Other CNS depressants (Benzodiazepines, Opioids, Sedative-hypnotics) Additive sedation and respiratory depression Use with caution; counsel patients; monitor for excessive sedation

Interacting Drug Effect Management

Carbamazepine ↓ Brivaracetam levels (enzyme induction); Brivaracetam may ↑ carbamazepine-epoxide levels Monitor for carbamazepine toxicity (diplopia, ataxia, nausea); consider dose adjustment

Phenytoin Brivaracetam may ↑ phenytoin levels slightly Monitor phenytoin levels; adjust if toxicity symptoms appear

Phenobarbital May ↓ Brivaracetam levels (enzyme induction) Monitor seizure control

Valproate Generally safe; no significant interaction Routine monitoring

Lamotrigine No significant pharmacokinetic interaction Safe to combine

Oral contraceptives No significant interaction No dose adjustment needed

Warfarin No known pharmacokinetic interaction Routine INR monitoring as standard practice

• Somnolence / drowsiness

• Dizziness

• Fatigue

• Headache

• Nausea

• Irritability

• Insomnia

• Nasopharyngitis

• Decreased appetite

Adverse Effect Notes

Suicidal ideation / behaviour Class effect of antiepileptics; monitor psychiatric status; counsel patients and caregivers

Psychiatric disturbances Aggression, agitation, anxiety, depression, psychotic symptoms — may require dose reduction or discontinuation

Hypersensitivity reactions Angioedema, bronchospasm, rash — discontinue immediately if severe

Status epilepticus Risk with abrupt discontinuation — always taper gradually

Neutropenia Rare; monitor if unexplained infections occur

After initiation (2–4 weeks) Clinical assessment for sedation, behavioural changes, mood disturbance; seizure diary review

During titration Seizure control; adverse effects; medication adherence

Long-term Periodic LFTs (especially in hepatic impairment); psychiatric status; seizure frequency; medication review

• Briviact® (UCB India)

• Brivazin® (Sun Pharma)

• Bricetum® (Torrent Pharmaceuticals)

• Brivetace® (Lupin)

• Brivamp® (Micro Labs)

• Brivera® (Intas)

Note: Not listed under NLEM; prices not NPPA-controlled. Price variation significant across brands and regions.

1. Better psychiatric tolerability than Levetiracetam: Consider Brivaracetam in patients who developed behavioural adverse effects (irritability, aggression, depression) on Levetiracetam — same mechanism but improved tolerability profile.

1. No titration mandatory: Unlike many antiepileptics, Brivaracetam can be initiated at therapeutic dose (50 mg twice daily) without mandatory slow titration — useful when rapid seizure control needed.

1. Oral-IV bioequivalence: Direct 1:1 dose conversion between oral and IV formulations; facilitates seamless transition during hospitalisation.

1. Avoid combining with Levetiracetam: Both bind SV2A — no additive efficacy expected, only additive adverse effects. Switch, do not add.

1. Hepatic impairment dose cap: Maximum 150 mg/day in any degree of hepatic impairment (reduce total daily dose by approximately one-third).

1. No effect on oral contraceptives: Unlike enzyme-inducing antiepileptics (Carbamazepine, Phenytoin), Brivaracetam does not reduce hormonal contraceptive efficacy.

brivaracetam; Briviact; antiepileptic; focal seizures; partial-onset seizures; SV2A ligand; levetiracetam-alternative; behavioural-friendly; IV formulation; neurology; epilepsy

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 Drug Formulary

• Indian Epilepsy Society clinical practice recommendations

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