Levetiracetam (Keppra) Treatment and Dosing in Epilepsy
Indications and FDA-Approved Uses
Levetiracetam is FDA-approved as adjunctive therapy for partial onset seizures (ages ≥4 years), myoclonic seizures in juvenile myoclonic epilepsy (ages ≥12 years), and primary generalized tonic-clonic seizures (ages ≥6 years). 1
Dosing for Partial Onset Seizures
Adults (≥16 years)
- Initiate treatment at 1000 mg/day in two divided doses (500 mg BID). 1
- Increase by 1000 mg/day increments every 2 weeks as needed. 1
- Maximum recommended dose is 3000 mg/day (1500 mg BID). 1
- Doses above 3000 mg/day have been studied but show no additional benefit. 1
- In clinical trials, doses of 1000 mg, 2000 mg, and 3000 mg all demonstrated efficacy, with responder rates (≥50% seizure reduction) ranging from 23-42% compared to 16-23% for placebo. 1
Pediatric Patients (4 to <16 years)
- Start at 20 mg/kg/day in two divided doses (10 mg/kg BID). 1
- Increase by 20 mg/kg/day increments every 2 weeks. 1
- Target dose is 60 mg/kg/day (30 mg/kg BID). 1
- If 60 mg/kg/day is not tolerated, the dose may be reduced; mean effective dose in trials was 52 mg/kg/day. 1
- Patients ≤20 kg should use oral solution; those >20 kg can use tablets or solution. 1
Weight-based tablet dosing guide for children: 1
- 20.1-40 kg: Start 500 mg/day (250 mg BID) → titrate to 1500 mg/day (750 mg BID)
- >40 kg: Start 1000 mg/day (500 mg BID) → titrate to 3000 mg/day (1500 mg BID)
Dosing for Myoclonic Seizures (Juvenile Myoclonic Epilepsy)
Patients ≥12 years
- Start at 1000 mg/day in two divided doses (500 mg BID). 1
- Increase by 1000 mg/day every 2 weeks. 1
- Recommended dose is 3000 mg/day (1500 mg BID). 1
- Efficacy of doses <3000 mg/day has not been established; at 3000 mg/day, 60.4% of patients achieved ≥50% reduction in myoclonic seizure days compared to 23.7% with placebo. 1
Dosing for Primary Generalized Tonic-Clonic Seizures
Adults (≥16 years)
- Start at 1000 mg/day in two divided doses (500 mg BID). 1
- Increase by 1000 mg/day every 2 weeks to 3000 mg/day. 1
- Doses <3000 mg/day have not been adequately studied for this indication. 1
Pediatric Patients (6 to <16 years)
- Start at 20 mg/kg/day in two divided doses (10 mg/kg BID). 1
- Increase by 20 mg/kg/day every 2 weeks to 60 mg/kg/day (30 mg/kg BID). 1
- Doses <60 mg/kg/day have not been adequately studied. 1
Status Epilepticus: IV Dosing
For status epilepticus refractory to benzodiazepines, levetiracetam is recommended as a second-line agent at 30 mg/kg IV over 5 minutes, with efficacy of 68-73%. 2, 3
Loading Dose Protocol
- Standard loading dose: 30 mg/kg IV at 5 mg/kg/minute. 2
- Alternative studied dosing: 1500-2500 mg IV over 5 minutes (particularly in elderly patients, showing 89% seizure reduction and 78% complete cessation). 2
- Lower doses of 20 mg/kg show reduced efficacy (38-67%) and are not recommended. 2, 4
- For emergency department loading in known seizure patients: 1500 mg oral or rapid IV (up to 60 mg/kg has been well tolerated). 2
Maintenance After Loading
- Maintenance dosing: 500-1500 mg every 12 hours based on clinical response. 2
Comparative Efficacy in Status Epilepticus
- Levetiracetam shows similar efficacy to valproate (73% vs 68% seizure cessation) when both used at 30 mg/kg IV. 2, 3
- Levetiracetam has minimal adverse effects compared to phenytoin (which causes hypotension in 12% of patients) and valproate. 2, 3
- Common side effects include fatigue, dizziness, rarely nausea or transient transaminitis. 2
Administration Guidelines
- Levetiracetam can be taken with or without food. 1
- For oral solution in pediatric patients, use a calibrated measuring device, not household spoons. 1
- IV formulations can be used interchangeably with oral formulations. 5
Clinical Considerations and Safety Profile
Tolerability
- Levetiracetam is generally well tolerated with an adverse event profile similar to placebo. 6, 7, 8
- Most common CNS-related effects: somnolence, asthenia, headache, dizziness. 6, 7
- Not associated with cognitive impairment or weight gain, but behavioral adverse effects occur in some patients. 7, 8
Drug Interactions
- Levetiracetam has no clinically significant drug interactions with other antiepileptic drugs, digoxin, warfarin, probenecid, or oral contraceptives. 6, 7, 8
- Lacks cytochrome P450 enzyme-inducing potential. 7, 8
- Primarily renally eliminated with minimal hepatic metabolism. 7, 8, 5
Efficacy Data
- In adjunctive therapy for refractory partial seizures, approximately 15% of patients on 1000 mg/day and 20-30% on 3000 mg/day achieve ≥50% seizure reduction. 9
- Clear dose-response relationship exists, with increasing efficacy at higher doses. 9
Critical Pitfalls to Avoid
- Do not use doses <30 mg/kg IV for status epilepticus, as efficacy drops significantly. 2
- Do not skip directly to third-line agents (anesthetics) without trying levetiracetam or another second-line agent after benzodiazepine failure. 3
- For myoclonic and primary generalized tonic-clonic seizures, doses below the recommended 3000 mg/day (or 60 mg/kg/day in children) lack adequate evidence. 1
- When using IV levetiracetam with other sedatives, prepare respiratory support and monitor oxygen saturation. 4