What is the recommended dosage and treatment protocol for Keppra (levetiracetam) in managing seizures?

Levetiracetam (Keppra) Dosing Protocol for Seizure Management

For managing seizures in adults, levetiracetam (Keppra) should be initiated at 1000 mg/day (500 mg twice daily), with increases of 1000 mg/day every 2 weeks to a maximum recommended dose of 3000 mg/day (1500 mg twice daily). 1

Adult Dosing (16 years and older)

Partial Onset Seizures

• Initial dose: 1000 mg/day, given as 500 mg twice daily 1
• Titration: Increase by 1000 mg/day every 2 weeks 1
• Maximum recommended dose: 3000 mg/day 1
• Administration: Can be given with or without food 1

Myoclonic Seizures (12 years and older with juvenile myoclonic epilepsy)

• Initial dose: 1000 mg/day, given as 500 mg twice daily 1
• Titration: Increase by 1000 mg/day every 2 weeks 1
• Target dose: 3000 mg/day (effectiveness of lower doses not well established) 1

Primary Generalized Tonic-Clonic Seizures

• Initial dose: 1000 mg/day, given as 500 mg twice daily 1
• Titration: Increase by 1000 mg/day every 2 weeks 1
• Target dose: 3000 mg/day (effectiveness of lower doses not well established) 1

Pediatric Dosing

Ages 4 to <16 Years

• Initial dose: 20 mg/kg/day in 2 divided doses (10 mg/kg twice daily) 1
• Titration: Increase by 20 mg/kg/day every 2 weeks 1
• Target dose: 60 mg/kg/day (30 mg/kg twice daily) 1
• Mean effective dose in clinical trials: 52 mg/kg/day 1

Status Epilepticus Management

For refractory status epilepticus (after benzodiazepines):

• Loading dose: 20-30 mg/kg IV 2
• Administration rate: 5 mg/kg/minute 2
• Efficacy: 67-73% seizure cessation in refractory status epilepticus 2

In elderly patients (≥65 years):

• Loading dose: 1500 mg IV over ≤15 minutes has shown 78% seizure cessation 2

Special Situations

Seizure Prophylaxis

• For patients with CNS disease or history of seizures: 10 mg/kg (up to maximum 500 mg) every 12 hours for 30 days 2
• For neurocritical care patients (SAH or TBI): 1000 mg twice daily appears more effective than 500 mg twice daily for prophylaxis 3

Oral Loading

• For rapid initiation: 1500 mg single oral dose followed by maintenance dose of 500-1000 mg twice daily starting 12 hours later 4
• This approach yields therapeutic serum concentrations within 1-2 hours and is well-tolerated with minimal side effects (11% reported mild transient effects) 4

Efficacy Considerations

• Approximately 15% of patients taking 1000 mg/day and 20-30% of patients taking 3000 mg/day achieve ≥50% reduction in seizure frequency 5
• In newly diagnosed epilepsy, levetiracetam 500 mg twice daily has shown comparable efficacy to controlled-release carbamazepine 6
• About 80% of patients achieving 6-month remission do so at the lowest dose level 6

Adverse Effects

• Common side effects: somnolence, dizziness, infection, and asthenia 7
• Levetiracetam is generally well-tolerated with minimal risk of adverse drug interactions 2
• Dose adjustments may be necessary in patients with renal dysfunction 2
• Withdrawal rates due to adverse events (14.4%) are lower than some other antiepileptic drugs 6

Important Clinical Considerations

• Levetiracetam has minimal protein binding (10%) and minimal hepatic metabolism, reducing drug interaction potential 7
• Steady state is achieved in approximately 2 days with twice-daily administration 7
• For status epilepticus, levetiracetam may be considered after benzodiazepines, with efficacy comparable to valproate 2
• Avoid abrupt discontinuation to prevent withdrawal seizures 2
• Use calibrated measuring devices for oral solution administration 1

Levetiracetam's favorable safety profile, minimal drug interactions, and rapid titration potential make it a valuable option for seizure management across various clinical scenarios.