Levetiracetam (Keppra) Dosing for Epilepsy
The standard adult dosing regimen for levetiracetam (Keppra) in epilepsy treatment is 1000 mg/day (500 mg twice daily) initially, with titration up to 3000 mg/day (1500 mg twice daily) based on clinical response. 1
Adult Dosing Protocol
Initial Dosing
- Start with 500 mg twice daily (1000 mg/day) 1
- Administer with or without food 1
- Can be given as tablets or oral solution 1
Titration Schedule
- Increase by 1000 mg/day (500 mg twice daily) every 2 weeks 1
- Maximum recommended dose: 3000 mg/day (1500 mg twice daily) 1
- Doses above 3000 mg/day have been used in open-label studies but without evidence of additional benefit 1
Seizure Type-Specific Dosing
- Partial onset seizures: Start at 500 mg twice daily, titrate as above 1
- Myoclonic seizures (age ≥12 years): Start at 500 mg twice daily, titrate to 3000 mg/day 1
- Primary generalized tonic-clonic seizures: Start at 500 mg twice daily, titrate to 3000 mg/day 1
Pediatric Dosing
Ages 4 to <16 years
- Initial dose: 20 mg/kg/day divided into two doses (10 mg/kg twice daily) 1
- Increase by 20 mg/kg/day every 2 weeks 1
- Target dose: 60 mg/kg/day (30 mg/kg twice daily) 1
- For children ≤20 kg: Use oral solution 1
- For children >20 kg: Can use tablets or oral solution 1
Weight-Based Tablet Dosing Guide
- 20.1-40 kg:
- Initial: 250 mg twice daily
- Target: 750 mg twice daily
40 kg:
- Initial: 500 mg twice daily
- Target: 1500 mg twice daily 1
Dosing in Special Populations
Renal Impairment
Dosage must be adjusted based on creatinine clearance: 1
| Creatinine Clearance | Dosage | Frequency |
|---|---|---|
| >80 mL/min (Normal) | 500-1500 mg | Every 12h |
| 50-80 mL/min (Mild) | 500-1000 mg | Every 12h |
| 30-50 mL/min (Moderate) | 250-750 mg | Every 12h |
| <30 mL/min (Severe) | 250-500 mg | Every 12h |
| ESRD on dialysis | 500-1000 mg | Every 24h* |
*A 250-500 mg supplemental dose is recommended following dialysis 1
Special Situations
- Status epilepticus: Loading dose of 30 mg/kg IV (max 2500 mg) administered at 5 mg/kg per minute 2
- CAR T-cell therapy with CNS disease/seizure history: 10 mg/kg (max 500 mg per dose) every 12 hours for 30 days 3
Efficacy and Tolerability
- Levetiracetam is generally well-tolerated with minimal drug interactions 2, 4
- Most common adverse effects include somnolence (10.5-15.2%), asthenia, dizziness, and irritability 2, 5
- Approximately 89% of patients do not report significant adverse effects 2
- Behavioral adverse effects occur in approximately 12-15% of patients 2
- Dose adjustments are not necessary in hepatic impairment but are required in renal impairment 1
Important Considerations
- Levetiracetam has minimal protein binding (10%) and does not interact with hepatically metabolized medications 5
- Abrupt discontinuation may precipitate status epilepticus; always taper gradually when discontinuing 2
- Monitor for irritability and behavioral changes, particularly in patients with history of psychiatric disorders 2
- Efficacy is dose-dependent, with approximately 15% of patients responding at 1000 mg/day and 20-30% responding at 3000 mg/day 6
Levetiracetam's favorable pharmacokinetic profile makes it particularly suitable for elderly patients and those on complex medication regimens due to minimal drug interactions 7.