Levetiracetam (Keppra) Dosing for Seizure Control
The recommended dosage of levetiracetam for seizure control in adults is 1000-3000 mg/day, typically starting at 500 mg twice daily with gradual increases of 1000 mg/day every 2 weeks to a maximum of 3000 mg/day based on response and tolerability. 1
Adult Dosing Guidelines
Initial Dosing
Titration
- Increase by 1000 mg/day every 2 weeks as needed 1
- Maximum recommended daily dose: 3000 mg/day 1
- Higher doses (>3000 mg/day) have been used in open-label studies but without clear evidence of additional benefit 1
Dosing by Seizure Type
Partial Onset Seizures (Adults ≥16 years)
- Initial: 500 mg twice daily
- Titration: Additional 1000 mg/day every 2 weeks
- Target: Up to 3000 mg/day (1500 mg twice daily) 1
Myoclonic Seizures (≥12 years with Juvenile Myoclonic Epilepsy)
Primary Generalized Tonic-Clonic Seizures (Adults ≥16 years)
- Initial: 500 mg twice daily
- Titration: Additional 1000 mg/day every 2 weeks
- Target: 3000 mg/day (1500 mg twice daily) 1
Pediatric Dosing
Children 4 to <16 years (Partial Onset Seizures)
- Initial: 20 mg/kg/day in 2 divided doses (10 mg/kg twice daily)
- Titration: Increase by 20 mg/kg/day every 2 weeks
- Target: 60 mg/kg/day (30 mg/kg twice daily) 1
- Mean daily dose in clinical trials: 52 mg/kg 1
Children 6 to <16 years (Primary Generalized Tonic-Clonic Seizures)
- Initial: 20 mg/kg/day in 2 divided doses (10 mg/kg twice daily)
- Titration: Increase by 20 mg/kg/day every 2 weeks
- Target: 60 mg/kg/day (30 mg/kg twice daily) 1
Dosing in Special Situations
Seizure Prophylaxis
- For neurocritical care patients (TBI, SAH): 500-750 mg twice daily 2
- Recent evidence suggests that doses >1000 mg/day (typically 1000 mg twice daily) may be more effective for seizure prophylaxis than lower doses (500 mg twice daily) 3
Status Epilepticus
- Loading dose: 30 mg/kg IV (maximum 2500 mg) administered at 5 mg/kg per minute 2
- Efficacy in refractory status epilepticus: 67-73% 2
- A dose of 1500 mg has been shown to resolve status epilepticus in 78% of patients within 30 minutes 2
Renal Impairment
Dosage adjustment required based on creatinine clearance:
- Normal (>80 mL/min): 500-1500 mg every 12 hours
- Mild impairment (50-80 mL/min): 500-1000 mg every 12 hours
- Moderate impairment (30-50 mL/min): 250-750 mg every 12 hours
- Severe impairment (<30 mL/min): 250-500 mg every 12 hours
- ESRD patients on dialysis: 500-1000 mg every 24 hours (with supplemental 250-500 mg dose following dialysis) 1
Efficacy and Tolerability
- In clinical trials, levetiracetam demonstrated equivalent seizure freedom rates to controlled-release carbamazepine in newly diagnosed epilepsy 4
- Most patients respond at lower doses, with 80.1% of those achieving 6-month remission doing so at the lowest dose level 4
- Common adverse effects include somnolence (10.5-15.2%), asthenia, dizziness, and irritability 2
- Approximately 89% of patients do not report significant adverse effects after levetiracetam loading dose 2
Clinical Pearls
- Levetiracetam has a favorable side effect profile compared to many other antiepileptic drugs, with less sedation than valproate 2
- Abrupt discontinuation can precipitate status epilepticus; always taper gradually when discontinuing 2
- Monitor for behavioral side effects, which occur in approximately 12-15% of patients 2
- Levetiracetam has a low potential for drug interactions, making it suitable for patients on multiple medications 5
Remember that while these are general dosing guidelines, clinical response and tolerability should guide individual dosing decisions, particularly when treating refractory seizures.