Schedule H

Oral, Intravenous

• Tablets (Immediate-Release): 250 mg, 500 mg, 750 mg, 1000 mg

• Extended-Release Tablets: 500 mg, 750 mg, 1000 mg

• Oral Solution: 100 mg/mL

• Injection (IV): 500 mg/5 mL (100 mg/mL)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Focal (Partial-Onset) Seizures — with or without secondary generalisation

Adults — Monotherapy or Adjunctive Therapy:

Parameter Recommendation

Starting dose 500 mg orally twice daily

Titration Increase by 500 mg twice daily every 2 weeks based on response and tolerability

Usual maintenance dose 1000–3000 mg/day in 2 divided doses

Maximum dose 3000 mg/day

Clinical Notes:

• May be used as monotherapy or adjunctive therapy

• IV formulation bioequivalent to oral — same dose, administer over 15 minutes

• Extended-release tablets allow once-daily dosing in stable patients

1. Myoclonic Seizures in Juvenile Myoclonic Epilepsy

Adults — Adjunctive Therapy Only:

Parameter Recommendation

Starting dose 500 mg orally twice daily

Titration Increase by 500 mg twice daily every 2 weeks

Usual maintenance dose 1000–3000 mg/day in 2 divided doses

Maximum dose 3000 mg/day

Clinical Notes:

• Approved only as adjunctive therapy — not for monotherapy in myoclonic seizures

• Age ≥12 years for this indication

1. Primary Generalised Tonic-Clonic Seizures in Idiopathic Generalised Epilepsy

Adults — Adjunctive Therapy:

Parameter Recommendation

Starting dose 500 mg orally twice daily

Titration Increase by 500–1000 mg/day every 2–4 weeks

Usual maintenance dose 1000–3000 mg/day in 2 divided doses

Maximum dose 3000 mg/day

Clinical Notes:

• Effective for generalised tonic-clonic seizures in idiopathic generalised epilepsy

• Age ≥12 years for this indication

1. Intravenous Use — When Oral Administration Not Feasible

Parameter Recommendation

Dose Same as oral dosing — 1:1 dose equivalence

Administration Dilute in NS/D5W/RL and infuse over 15 minutes

Duration of IV use Transition to oral as soon as feasible

Secondary Indications – Adults Only (Off-label)

Indication Dose Duration Supervision Evidence Basis

Status Epilepticus — Adjunctive Therapy — OFF-LABEL Loading: 1000–3000 mg IV over 15 minutes; Maintenance: 500–1500 mg BD Until seizure control achieved and oral transition possible Specialist/ICU only Indian tertiary hospital protocols; supportive RCTs

Post-Traumatic Seizure Prophylaxis — OFF-LABEL 500 mg BD starting within 24 hours of injury 7 days post-injury (short-term prophylaxis only) Neurosurgery/Critical Care AIIMS protocols; international RCTs

PAEDIATRIC DOSING (Specialist Only)

Primary Indications: Focal Seizures, Myoclonic Seizures, Generalised Tonic-Clonic Seizures

Age Restriction: Not recommended below 1 month of age. Use below 6 months only under specialist paediatric neurology supervision.

Weight-Based Dosing Table

1–6 months 7 mg/kg orally twice daily Increase by 7 mg/kg BD every 2 weeks 21 mg/kg twice daily 42 mg/kg/day

6 months – <4 years 10 mg/kg orally twice daily Increase by 10 mg/kg BD every 2 weeks 25 mg/kg twice daily 50 mg/kg/day

4 – <16 years 10 mg/kg (max 250 mg) orally twice daily Increase by 10 mg/kg BD every 2 weeks 30 mg/kg twice daily 60 mg/kg/day (max 3000 mg/day)

≥16 years Adult dosing applies — — 3000 mg/day

Formulation Notes:

• Use oral solution (100 mg/mL) for accurate weight-based dosing in younger children

• Tablets appropriate for children ≥20 kg who can swallow whole tablets

• IV dosing same as oral — infuse over 15 minutes

Safety Monitoring:

• Monitor for behavioural changes (irritability, aggression, mood swings)

• Assess sedation and psychomotor development

• Educate caregivers about behavioural adverse effects

Secondary Indications – Paediatric (Off-label)

Indication Dose Notes Evidence Basis

Adjunctive therapy in Dravet Syndrome — OFF-LABEL Individualised; often 20–40 mg/kg/day Specialist only; usually combined with valproate or clobazam Indian paediatric neurology practice

Neonatal Seizures — OFF-LABEL Loading: 20–40 mg/kg IV; Maintenance: 10–30 mg/kg BD NICU setting only; specialist supervision mandatory Tertiary NICU protocols

Levetiracetam is primarily renally excreted — dose reduction required in renal impairment:

ESRD on haemodialysis 500–1000 mg once daily; give supplemental dose of 250–500 mg after each dialysis session

Notes:

• Use oral solution for precise dose titration in severe impairment

• Peritoneal dialysis: limited data; use haemodialysis recommendations as guide

Note: Levetiracetam undergoes minimal hepatic metabolism — safe choice in patients with liver disease.

• Known hypersensitivity to levetiracetam, other pyrrolidone derivatives, or any excipient

• History of severe psychiatric reaction (psychosis, severe aggression) attributable to levetiracetam — relative contraindication; avoid rechallenge

• Pre-existing psychiatric disorders (depression, anxiety, psychosis) — risk of exacerbation

• History of behavioural disturbances — increased risk of irritability and aggression

• Suicidal ideation risk — monitor mood, especially in adolescents and young adults

• Renal impairment — dose adjustment mandatory

• Elderly with cognitive impairment — enhanced CNS sensitivity

• Abrupt withdrawal — taper gradually over 2–4 weeks to avoid rebound seizures

• Driving and operating machinery — advise caution due to somnolence risk

Parameter Details

Risk category Relatively low teratogenic risk compared to older AEDs (valproate, phenytoin, carbamazepine)

Preferred alternatives Levetiracetam or lamotrigine preferred in Indian obstetric/neurology practice when AED required

When may be used May be continued in pregnancy if seizure control established; avoid switching AEDs during pregnancy if possible

Monitoring Folic acid 5 mg/day from preconception through first trimester; monitor maternal seizure control; targeted anomaly scan; monitor drug levels (clearance increases in pregnancy)

Neonatal concerns Monitor neonate for withdrawal symptoms (rare); vitamin K prophylaxis as standard

Parameter Details

Compatibility Compatible with breastfeeding

Drug levels in milk Low to moderate (infant receives approximately 3–8% of maternal weight-adjusted dose)

Preferred alternatives Levetiracetam is among preferred AEDs for lactating women; lamotrigine also acceptable

Infant monitoring Observe for sedation, irritability, poor feeding, weight gain; monitor developmental milestones

Parameter Recommendation

Starting dose 250 mg twice daily

Titration Slower titration — increase by 250 mg twice daily every 2 weeks

Special risks Increased risk of somnolence, dizziness, falls, cognitive impairment; higher prevalence of occult renal impairment — check eGFR before dosing

Formulation Oral solution preferred for flexible dose adjustment

Drug/Class Mechanism/Effect Recommendation

Methotrexate Levetiracetam may reduce renal clearance of methotrexate → increased methotrexate toxicity Monitor for methotrexate toxicity (mucositis, myelosuppression); consider dose adjustment

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

Note: Levetiracetam does not induce or inhibit CYP450 enzymes — minimal hepatic drug interaction potential.

Drug/Class Effect Recommendation

Carbamazepine Minor pharmacokinetic interaction; possible slight increase in carbamazepine-epoxide Monitor for carbamazepine toxicity symptoms (diplopia, ataxia)

Other antiepileptics (valproate, phenytoin, phenobarbital) No significant pharmacokinetic interactions; may have additive CNS effects Standard monitoring; generally safe combination

Warfarin Theoretical interaction (not CYP-mediated) Monitor INR when initiating or stopping levetiracetam

Antidepressants/Antipsychotics Additive risk of behavioural adverse effects Monitor mood and behaviour closely

Oral contraceptives No enzyme induction — does not reduce contraceptive efficacy Safe combination; no additional contraception required

• Somnolence / drowsiness

• Dizziness

• Asthenia / fatigue

• Irritability and behavioural changes

• Headache

• Nasopharyngitis / upper respiratory infections

• Decreased appetite

• Mood changes (anxiety, emotional lability)

Adverse Effect Clinical Action

Severe behavioural disturbance (psychosis, aggression, hostility) Consider dose reduction or discontinuation; psychiatric evaluation

Suicidal ideation or behaviour Immediate psychiatric referral; consider drug discontinuation

Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis Immediate discontinuation and hospitalisation — rare but reported

Anaphylaxis / Angioedema Discontinue immediately; emergency management

DRESS syndrome Rare; discontinue and supportive care

Pancytopenia / Agranulocytosis Very rare; discontinue and investigate

Rhabdomyolysis Rare; check CK if myalgia/weakness prominent

Baseline:

• Renal function (serum creatinine, eGFR)

• Seizure history and frequency documentation

• Psychiatric history assessment

• Pregnancy test in women of childbearing age

After Initiation / Dose Change:

• Mental status and behavioural assessment at 2–4 weeks

• Seizure frequency monitoring

• Assessment for irritability, mood changes (especially in children and adolescents)

• Evaluate for somnolence and cognitive effects

Long-term Monitoring:

• Renal function annually (more frequently in elderly or renal impairment)

• Behavioural and mood assessment at each visit

• Growth parameters in children

• Seizure diary review

• Periodic assessment of need for continued therapy

Note: Routine serum drug level monitoring not required — clinical response guides dosing. Therapeutic drug monitoring may be considered in pregnancy, renal impairment, or suspected non-adherence.

Single-Ingredient Formulations:

• Keppra (UCB)

• Levipil (Sun Pharma)

• Torleva (Torrent)

• Levera (Intas)

• Levesam (Mankind)

• Levroxa (Macleods)

• Epitero (Cipla)

• Levegard (Zydus)

Extended-Release Formulations:

• Levipil XR (Sun Pharma)

• Torleva XR (Torrent)

IV Formulations:

• Keppra IV (UCB)

• Levipil IV (Sun Pharma)

• Not currently included in NLEM 2022

• Available in government hospitals through neurology programmes

• Significant brand-to-brand price variation — generic options more affordable

1. Preferred AED in hepatic impairment — minimal hepatic metabolism makes levetiracetam ideal for patients with liver disease or those on multiple hepatically metabolised drugs

1. No enzyme induction — unlike carbamazepine and phenytoin, does not reduce efficacy of oral contraceptives, warfarin, or other CYP-metabolised drugs

1. Behavioural adverse effects are common — especially irritability and aggression in children; counsel caregivers at initiation and monitor closely; pyridoxine (vitamin B6) supplementation sometimes used empirically to mitigate behavioural effects

1. Seamless IV-to-oral transition — bioequivalent formulations allow direct 1:1 dose conversion without adjustment

1. Gradual withdrawal essential — even in seizure-free patients, abrupt discontinuation may precipitate rebound seizures; taper over 2–4 weeks minimum

1. Pregnancy-compatible AED — among the safer antiepileptics for use during pregnancy; preferred over valproate, phenytoin, and carbamazepine when new AED initiation required in women of childbearing potential

1. Renal dosing mandatory in elderly — age-related decline in renal function often unrecognised; always calculate eGFR before prescribing

antiepileptic; epilepsy; focal seizures; myoclonic seizures; generalised tonic-clonic; levetiracetam; renal-adjustment; liver-safe; pregnancy-preferred; paediatric-epilepsy; no-enzyme-induction; Schedule H

RxIndia v1.0 — 05 Jun 2025

• CDSCO approved product inserts

• Indian Pharmacopoeia

• API Textbook of Medicine

• AIIMS Epilepsy Management Protocol

• ICMR Guidelines on Neurological Disorders

• IAP Paediatric Drug Formulary

• Indian Epilepsy Society recommendations

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

• Harrison's Principles of Internal Medicine (supportive)

• International RCTs for off-label status epilepticus use