What is the recommended dose and duration of Keppra (levetiracetam) prophylaxis for seizure prevention?

Levetiracetam (Keppra) Prophylaxis for Seizure Prevention

For seizure prophylaxis in adults, levetiracetam should be administered at a dose of 1000-3000 mg/day divided twice daily, with most evidence supporting 2000 mg/day (1000 mg twice daily) for optimal efficacy, and treatment should be limited to 7 days unless ongoing seizure activity is present. 1, 2

Dosing Recommendations

Initial Dosing

• For adults requiring seizure prophylaxis, start with 1000 mg/day given as 500 mg twice daily 1
• Increase to 2000 mg/day (1000 mg twice daily) for optimal prophylaxis, as this dosage has shown better seizure prevention compared to lower doses 3
• Maximum recommended daily dose is 3000 mg/day (1500 mg twice daily) 1

Special Considerations

• Levetiracetam can be administered orally or intravenously with equivalent efficacy 1
• No therapeutic drug monitoring is required, unlike phenytoin, making it easier to manage in acute settings 4
• Dose adjustments are necessary for patients with renal impairment 1

Duration of Therapy

Acute Seizure Prophylaxis

• Short-term prophylaxis (≤7 days) is recommended for most patients requiring seizure prevention 2
• Continuing prophylaxis beyond 7 days does not prevent the development of post-traumatic epilepsy and may lead to unnecessary side effects 5, 2
• In a military cohort study, only 2% of patients received the recommended 1-week prophylaxis, while 42% received extended prophylaxis (mean 6.2 months) without additional benefit 5

Extended Treatment

• For patients who experience seizures during the prophylactic period, continued treatment is indicated until the underlying cause is controlled 4
• In patients with subdural hemorrhage who have had seizures, continue levetiracetam until local control of the hemorrhage has been achieved 4

Efficacy Compared to Other Agents

• Levetiracetam, fosphenytoin, and valproate have similar efficacy for seizure control in status epilepticus, with cessation of seizure activity in approximately 45-47% of cases 6
• The ESETT trial demonstrated no significant difference between these three agents in terminating status epilepticus 6
• Levetiracetam may have advantages over phenytoin including:
  • Fewer adverse effects (0.7% hypotension with levetiracetam vs. 3.2% with fosphenytoin) 6
  • No need for therapeutic drug monitoring 4
  • No significant drug interactions with other medications commonly used in neurocritical care 4

Common Pitfalls and Caveats

• Underdosing: A study showed that patients receiving only 1000 mg/day had higher seizure incidence compared to those receiving >1000 mg/day (typically 2000 mg/day) 3
• Extended prophylaxis: Continuing levetiracetam beyond 7 days without documented seizures exposes patients to unnecessary side effects and has occupational implications 5, 2
• CSF penetration: Some evidence suggests levetiracetam may not reach therapeutic levels in CSF as quickly as phenytoin when using standard loading doses 7
• Monitoring: While serum level monitoring is not required, patients should be monitored for psychiatric side effects 4

Special Situations

• For patients with impaired or fluctuating consciousness disproportionate to their brain injury, consider continuous EEG monitoring for at least 24 hours to detect subclinical seizures 4
• In patients with status epilepticus refractory to benzodiazepines, levetiracetam can be administered at 30-60 mg/kg IV as a loading dose 6
• For patients with traumatic brain injury, the Neurocritical Care Society suggests levetiracetam over phenytoin/fosphenytoin for seizure prophylaxis (weak recommendation, very low quality of evidence) 2