What is the recommended loading dose of Keppra (levetiracetam)?

Recommended Loading Dose of Levetiracetam (Keppra)

The recommended loading dose of levetiracetam (Keppra) is 30-50 mg/kg IV administered over 15 minutes, with typical adult loading doses ranging from 1000-3000 mg. 1

Dosing Guidelines

Initial Loading Dose

• For adults requiring rapid achievement of therapeutic levels:
  • Loading dose: 30-50 mg/kg IV 1
  • Typical fixed doses: 1000-3000 mg IV 2
  • Administration: Infuse over 15 minutes 2
  • Do not further dilute the solution prior to use 2

Formulations Available

Levetiracetam in Sodium Chloride Injection is available in three single-dose 100 mL bags 2:

• 500 mg (5 mg/mL)
• 1000 mg (10 mg/mL)
• 1500 mg (15 mg/mL)

Maintenance Dosing

After loading dose, transition to maintenance dosing:

• Initial maintenance: 500 mg twice daily 2
• Titration: Increase by 1000 mg/day every 2 weeks as needed 2
• Maximum recommended daily dose: 3000 mg (1500 mg twice daily) 2
• For patients already on oral levetiracetam, maintain equivalent total daily dosage and frequency 2

Efficacy and Safety Considerations

Efficacy

• High-dose levetiracetam (750-1000 mg twice daily) is more than twice as likely to achieve target serum levels compared to low-dose regimens (500 mg twice daily) 3
• Target therapeutic serum concentration: 12-46 μg/mL 3
• Higher doses (750-1000 mg twice daily) reduced the odds of seizure by 68% compared to low doses 3

Safety Profile

• Loading doses up to 60 mg/kg (maximum 3000 mg) have been administered safely with minimal dilution 4
• No significant changes in blood pressure, no local infusion site reactions, and no ECG abnormalities were observed with high loading doses 4
• Oral loading with 1500 mg was well-tolerated with minimal side effects (11% of patients reported mild transient symptoms) 5
• IV push administration of doses up to 4000 mg showed similar safety profile to IV piggyback infusion 6

Special Populations

Renal Impairment

Dosing must be adjusted based on creatinine clearance 2:

• Normal (>80 mL/min): Standard dosing
• 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 250-500 mg supplemental dose following dialysis

Common Adverse Effects

• Most common: Somnolence, asthenia, infection, and dizziness 2
• Frequency and severity of adverse effects (particularly somnolence and asthenia) may increase with higher doses 7

Clinical Pearls

• Rapid achievement of therapeutic levels is possible with loading doses
• No further dilution of the IV formulation is required prior to use
• Avoid abrupt withdrawal to reduce risk of increased seizure frequency and status epilepticus 2
• IV levetiracetam is physically compatible with lorazepam, diazepam, and valproate sodium for at least 24 hours 2

By using appropriate loading doses of levetiracetam, clinicians can rapidly achieve therapeutic serum concentrations with a favorable safety profile, potentially improving seizure control outcomes in patients requiring urgent treatment.