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

Recommended Loading Dose for Levetiracetam (Keppra)

The recommended loading dose for levetiracetam (Keppra) is 30 mg/kg IV administered over 15 minutes, with a maximum of 2,500 mg. 1

Dosing Guidelines by Clinical Context

Status Epilepticus

• Loading dose: 30 mg/kg IV over 15 minutes 1
• Maximum single dose: 2,500 mg 2
• Efficacy in status epilepticus: 73% seizure cessation rate 1

Routine Initiation (when oral administration is not feasible)

• Initial dose: 500 mg IV twice daily 2
• Titration: Increase by 500 mg twice daily every 2 weeks 2
• Maximum recommended maintenance dose: 1,500 mg twice daily (3,000 mg/day) 2

Administration Considerations

Infusion Parameters

• Standard infusion: Administer over 15 minutes 2
• Do not dilute prior to use 2
• Available in pre-mixed bags of 500 mg/100 mL, 1,000 mg/100 mL, and 1,500 mg/100 mL 2

Rapid Infusion Options

• Emerging evidence suggests that administration over 5 minutes appears safe and well-tolerated 3
• Rapid infusion may be beneficial in acute care settings requiring rapid attainment of therapeutic levels 3

Special Population Considerations

Renal Impairment

Dose adjustment required based on creatinine clearance 2:

• Normal (>80 mL/min): 500-1,500 mg every 12 hours
• Mild impairment (50-80 mL/min): 500-1,000 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

Pharmacokinetics After Loading

• After a 1,500 mg IV infusion, peak plasma concentration (Cmax) reaches approximately 50.5 μg/mL 4
• Bioequivalence between IV and oral formulations has been established 4
• Steady state is reached within 48 hours of regular dosing 4

Oral Loading Alternative

When IV administration is not available, oral loading may be considered:

• Oral loading dose: 1,500 mg as a single dose 5
• Maintenance: Begin 500-1,000 mg twice daily starting 12 hours after loading 5
• Serum concentrations after oral loading: ~30 μg/mL at 1-2 hours post-dose 5

Common Adverse Effects with Loading Doses

• Somnolence (33% with IV vs 17% with placebo) 4
• Postural dizziness (25% with IV vs 0% with placebo) 4
• Generally well-tolerated with minimal serious adverse effects 3, 4, 5

Clinical Pitfalls to Avoid

1. Underdosing: Only 54% of patients achieve target serum levels with low doses (500 mg twice daily); higher doses (750-1,000 mg twice daily) are more than twice as likely to achieve optimal drug levels 6

2. Inadequate monitoring: Monitor for adverse effects including somnolence, dizziness, and behavioral changes 2

3. Abrupt discontinuation: Gradually withdraw levetiracetam to reduce the risk of increased seizure frequency and status epilepticus 2

4. Compatibility issues: Levetiracetam is physically compatible with lorazepam, diazepam, and valproate sodium for at least 24 hours, but compatibility with other antiepileptic drugs is not established 2

In summary, while the FDA-approved loading dose for levetiracetam is not explicitly stated in the package insert, clinical evidence supports a loading dose of 30 mg/kg IV (maximum 2,500 mg) administered over 15 minutes for patients requiring rapid initiation of therapy, particularly in status epilepticus.