Keppra (Levetiracetam) Dosing for Epilepsy Management
Standard Maintenance Dosing for Chronic Epilepsy
For adults and adolescents ≥16 years with partial onset seizures, start levetiracetam at 1000 mg/day (500 mg twice daily) and increase by 1000 mg/day every 2 weeks up to the recommended dose of 3000 mg/day (1500 mg twice daily). 1
Adult Dosing by Seizure Type
Partial Onset Seizures:
- Initial dose: 1000 mg/day divided as 500 mg BID 1
- Titration: Increase by 1000 mg/day every 2 weeks 1
- Target dose: 3000 mg/day (maximum studied dose) 1
- Doses >3000 mg/day show no additional benefit 1
Myoclonic Seizures (≥12 years with juvenile myoclonic epilepsy):
- Initial dose: 1000 mg/day (500 mg BID) 1
- Titration: Increase by 1000 mg/day every 2 weeks 1
- Target dose: 3000 mg/day (doses <3000 mg/day not adequately studied) 1
Primary Generalized Tonic-Clonic Seizures (≥16 years):
- Initial dose: 1000 mg/day (500 mg BID) 1
- Titration: Increase by 1000 mg/day every 2 weeks 1
- Target dose: 3000 mg/day 1
Pediatric Maintenance Dosing
Children 4 to <16 years (Partial Onset Seizures):
- Initial dose: 20 mg/kg/day divided as 10 mg/kg BID 1
- Titration: Increase by 20 mg/kg every 2 weeks 1
- Target dose: 60 mg/kg/day (30 mg/kg BID) 1
- If 60 mg/kg/day not tolerated, may reduce dose 1
- Use oral solution for patients ≤20 kg; tablets or solution for >20 kg 1
Children 6 to <16 years (Primary Generalized Tonic-Clonic Seizures):
- Initial dose: 20 mg/kg/day (10 mg/kg BID) 1
- Titration: Increase by 20 mg/kg every 2 weeks 1
- Target dose: 60 mg/kg/day (30 mg/kg BID) 1
Acute/Emergency Dosing for Status Epilepticus
For status epilepticus in adults, administer levetiracetam 40-60 mg/kg IV (maximum 2500-4500 mg) as a loading dose over 5-15 minutes, which achieves 67-89% seizure termination within 24 hours. 2
Adult Loading Doses
- Standard loading: 1500-2500 mg IV over 5-15 minutes 2
- Weight-based loading: 40-60 mg/kg IV (maximum 2500-4500 mg) 2
- Efficacy: 67-89% seizure cessation within 24 hours 2, 3
- Key advantage: No hypotension risk, no cardiac monitoring required, no infusion rate limitations (unlike phenytoin) 2
Pediatric Loading Doses for Status Epilepticus
- Loading dose: 40 mg/kg IV bolus (maximum 2500 mg) 2
- Maintenance: 15-30 mg/kg IV every 12 hours 2
- Safety data supports 20,40, and 60 mg/kg loading doses with no significant blood pressure changes, infusion site reactions, or ECG abnormalities 2, 3
Alternative Acute Dosing
- For refractory status epilepticus: 20-30 mg/kg IV 3
- Efficacy as second/third-line agent: 67-73% seizure cessation 2
Special Situations: Seizure Prophylaxis
CAR T-Cell Therapy Prophylaxis:
- Adult dose: 500-750 mg orally every 12 hours for 30 days starting on infusion day 2
- Alternative pediatric dose: 10 mg/kg (maximum 500 mg) every 12 hours for 30 days 2, 3
Dose-Response and Efficacy Data
Efficacy increases with dose for partial seizures:
- 1000 mg/day: ~15% achieve ≥50% seizure reduction 4
- 3000 mg/day: 20-30% achieve ≥50% seizure reduction 4
- Responder rates (≥50% reduction): significantly higher at 2000 mg vs 1000 mg 5
- Seizure freedom rates: 5.5% at 1000 mg/day, 6.3% at 2000 mg/day vs 1.2% on placebo 5
Critical Pitfalls and Considerations
Common Dosing Errors:
- Avoid subtherapeutic dosing: Many studies used 250-500 mg BID, which is below FDA-recommended starting doses and may explain lack of efficacy in some prophylaxis trials 6
- Don't stop at 1000 mg/day: Dose-response data clearly shows improved efficacy at 2000-3000 mg/day 4, 5
Adverse Effects:
- Most common: somnolence and asthenia (frequency/severity increase with dose) 7
- 4000 mg/day may be upper tolerance limit for some patients 7
- Overall adverse event rate: ~8% with levetiracetam vs 21% with other antiseizure medications 6
- Transient irritability, imbalance, tiredness reported in only 11% during oral loading 3
Administration: