Levetiracetam (Keppra) Treatment for Epilepsy
The recommended treatment for epilepsy with levetiracetam (Keppra) is to start with 1000 mg/day (500 mg twice daily) for adults, with titration up to 3000 mg/day in 1000 mg increments every 2 weeks as needed, while children should start at 20 mg/kg/day divided into two doses with titration up to 60 mg/kg/day. 1
Indications
Levetiracetam is FDA-approved for:
- Adjunctive treatment of partial onset seizures in adults and children ≥4 years
- Adjunctive therapy for myoclonic seizures in adults and adolescents ≥12 years with juvenile myoclonic epilepsy
- Adjunctive therapy for primary generalized tonic-clonic seizures in adults and children ≥6 years with idiopathic generalized epilepsy 1
Dosing Guidelines by Age and Seizure Type
Adults (≥16 years)
Partial Onset Seizures:
- Initial dose: 1000 mg/day (500 mg twice daily)
- Titration: Increase by 1000 mg/day every 2 weeks
- Maximum recommended dose: 3000 mg/day (1500 mg twice daily) 1
Myoclonic Seizures (≥12 years):
- Initial dose: 1000 mg/day (500 mg twice daily)
- Titration: Increase by 1000 mg/day every 2 weeks
- Target dose: 3000 mg/day 1
Primary Generalized Tonic-Clonic Seizures:
- Initial dose: 1000 mg/day (500 mg twice daily)
- Titration: Increase by 1000 mg/day every 2 weeks
- Target dose: 3000 mg/day 1
Pediatric Patients
Ages 4 to <16 years (Partial Onset Seizures):
- Initial dose: 20 mg/kg/day in 2 divided doses
- Titration: Increase by 20 mg/kg every 2 weeks
- Target dose: 60 mg/kg/day (30 mg/kg twice daily) 1
Ages 6 to <16 years (Primary Generalized Tonic-Clonic Seizures):
- Initial dose: 20 mg/kg/day in 2 divided doses
- Titration: Increase by 20 mg/kg every 2 weeks
- Target dose: 60 mg/kg/day (30 mg/kg twice daily) 1
Administration Guidelines
- Levetiracetam can be taken with or without food 1
- For children ≤20 kg, use oral solution
- For children >20 kg, either tablets or oral solution can be used 1
- For patients with renal impairment, dose adjustment is required based on creatinine clearance 2:
- Creatinine clearance 50-80 ml/min: 500-1000 mg every 12 hours
Special Considerations
Seizure Prophylaxis
- For patients with CNS disease or history of seizures receiving CAR T-cell therapy, levetiracetam 10 mg/kg (maximum 500 mg per dose) every 12 hours for 30 days is recommended for seizure prophylaxis 3
Status Epilepticus
- Loading dose: 30 mg/kg IV (maximum 2500 mg) administered at 5 mg/kg per minute 2
- For children with status epilepticus: 30-50 mg/kg IV over 10-15 minutes 2
Efficacy and Safety Profile
- Levetiracetam has demonstrated efficacy with 67-73% control rate in refractory status epilepticus 2
- In clinical trials, levetiracetam showed dose-dependent efficacy with significantly decreased seizure frequency at doses of 1000,2000, and 3000 mg/day compared to placebo 4
- At 1000 mg/day, 5.5% of patients became seizure-free, and at 2000 mg/day, 6.3% became seizure-free 4
Common Adverse Effects
- Somnolence (10.5-15.2%)
- Asthenia
- Dizziness
- Irritability 2
Risk Factors for Adverse Effects
- Patients with intellectual disability or psychiatric history have higher risk (12-15%) of behavioral adverse effects 2
- For these high-risk patients, slower titration and closer monitoring are recommended 2
Clinical Pearls
- Approximately 89% of patients do not report significant adverse effects after loading doses 2
- Levetiracetam has minimal drug interactions, making it particularly useful for patients on multiple medications 2
- Most patients respond at lower doses - in clinical studies, 80.1% of patients achieving 6-month remission did so at the lowest dose level 5
- Doses above 3000 mg/day have been used in open-label studies but without evidence of additional benefit 1
- For children, doses above 20 mg/kg/day should be introduced with caution 2
Levetiracetam's favorable safety profile, minimal drug interactions, and proven efficacy make it a valuable option for epilepsy treatment across multiple seizure types and age groups.