What is the recommended dose and administration of Levetiracetam (Keppra) injection for an adult patient with a history of epilepsy or other seizure disorders?

Levetiracetam Injection for Seizures in Adults

Recommended Dosing and Administration

For status epilepticus refractory to benzodiazepines, administer levetiracetam 30 mg/kg IV (approximately 2000-3000 mg for average adults) over 5 minutes as a second-line agent. 1

Standard Loading Dose Protocol

• Administer 30 mg/kg IV over 5 minutes for benzodiazepine-refractory status epilepticus 1, 2
• This translates to approximately 2000-3000 mg for most adults 1
• Alternative studied dosing: 1500-2500 mg IV over 5-15 minutes 2
• Do not use lower doses (20 mg/kg) as they show significantly reduced efficacy (38% vs 68-73% with 30 mg/kg) 2, 3

Administration Details

• Administer undiluted as rapid IV push over 5 minutes 1, 2
• Can be given through peripheral IV (79.1% of administrations) 4
• No cardiac monitoring required (unlike phenytoin/fosphenytoin) 1
• Doses up to 4500 mg have been safely administered as rapid IV push 4

Clinical Context: When to Use Levetiracetam

Levetiracetam is a second-line agent for status epilepticus—use only after adequate benzodiazepine therapy has failed. 1

The treatment algorithm is:

1. First-line: Benzodiazepines (lorazepam 4 mg IV) 1
2. Second-line (if seizures continue): Levetiracetam 30 mg/kg IV OR valproate 20-30 mg/kg IV OR fosphenytoin 20 mg PE/kg IV 1
3. Third-line (refractory status epilepticus): Anesthetic agents (midazolam, propofol, or pentobarbital) 1

Efficacy Data

• 68-73% seizure cessation rate when used as second-line agent after benzodiazepines 1, 2
• Equivalent efficacy to valproate (73% vs 68%) when both used at 30 mg/kg 2
• Superior to lower doses: 30 mg/kg achieves 68-73% efficacy vs only 38% with 20 mg/kg 2, 3

Advantages Over Alternative Second-Line Agents

Levetiracetam offers significant practical advantages, particularly for elderly or hemodynamically unstable patients:

• No hypotension risk (0% vs 12% with fosphenytoin) 1
• No cardiac monitoring required (unlike phenytoin/fosphenytoin which require continuous ECG) 1
• Minimal adverse effects (fatigue, dizziness, rarely nausea) 2
• No drug interactions with other anticonvulsants 5
• Can be given rapidly (5 minutes vs 20+ minutes for phenytoin) 1, 2

Maintenance Dosing After Status Epilepticus

Once seizures are controlled, transition to maintenance therapy:

• For convulsive status epilepticus: 30 mg/kg IV every 12 hours OR increase to 20 mg/kg IV every 12 hours (maximum 1500 mg per dose) 1
• For non-convulsive status epilepticus: 15 mg/kg IV every 12 hours (maximum 1500 mg per dose) 1
• Standard maintenance for chronic epilepsy: 500-1500 mg IV twice daily 6

Critical Safety Considerations

Higher doses (>40 mg/kg) are associated with increased intubation rates without improved efficacy:

• Doses ≥40 mg/kg had 45.8% intubation rate vs 26.8-28.2% with lower doses 3
• No improvement in seizure termination with doses >40 mg/kg (84.7% vs 89-93% with lower doses) 3
• Stick to 30 mg/kg maximum for optimal risk-benefit ratio 1, 3

Monitoring Requirements

Post-administration monitoring protocol:

• First 2 hours: Vital signs and neurological assessment every 15 minutes 2
• Hours 2-8: Continue monitoring every 30 minutes 2
• Hours 8-24: Hourly monitoring for delayed adverse effects 2
• Watch for: Somnolence, sedation, injection site reactions (redness, burning) 2, 4
• No routine cardiac monitoring needed (major advantage over phenytoin) 1

Renal Dosing Adjustments

Dose adjustment necessary based on creatinine clearance per FDA labeling 6

Common Pitfalls to Avoid

• Do not use as first-line therapy—benzodiazepines must be tried first 1
• Do not underdose—20 mg/kg is inadequate; use 30 mg/kg 2, 3
• Do not exceed 40 mg/kg—higher doses increase intubation risk without benefit 3
• Do not dilute or give slowly—rapid undiluted administration over 5 minutes is safe and effective 2, 4
• Do not skip to third-line agents (pentobarbital, propofol) until levetiracetam or another second-line agent has been tried 1

Special Clinical Scenarios

For known epilepsy patients with breakthrough seizures (not status epilepticus):

• ED loading: 1500 mg oral or rapid IV 2
• Up to 60 mg/kg has been well tolerated in this population 2

For elderly or hemodynamically unstable patients:

• Levetiracetam is preferred over phenytoin/fosphenytoin due to zero hypotension risk 1
• No cardiac monitoring requirements make it ideal for resource-limited settings 1