What is the recommended intravenous (IV) dose and flow rate for Levetiracetam (Keppra) administration?

Levetiracetam IV Dosing and Administration Rate

For status epilepticus, administer levetiracetam 30 mg/kg IV (typically 2000-3000 mg for average adults) over 5 minutes, which is significantly faster than the FDA-labeled 15-minute infusion and achieves rapid therapeutic levels with minimal adverse effects. 1, 2

Standard Dosing for Status Epilepticus

The American College of Emergency Physicians recommends 30 mg/kg IV over 5 minutes as the second-line dose for benzodiazepine-refractory status epilepticus, with demonstrated efficacy of 68-73%. 1, 2

• For average adults, this translates to approximately 2000-3000 mg IV 1
• Lower doses of 20 mg/kg show significantly reduced efficacy (38% vs 68-73%) and should be avoided 2
• Alternative dosing of 1500-2500 mg IV over 5-15 minutes has shown 89% reduction in seizures with 78% complete cessation 2

FDA-Labeled Administration vs. Evidence-Based Practice

While the FDA label states levetiracetam should be administered over 15 minutes, extensive clinical evidence supports safe administration over 5 minutes or even faster. 3

• The FDA-approved rate is 15 minutes for all doses 3
• However, doses up to 4500 mg administered over 5-10 minutes have been proven safe and well-tolerated in multiple studies 4, 5
• Rapid infusion (2-5 minutes) significantly reduces time to administration (28 vs 80 minutes) and decreases interim benzodiazepine use (2% vs 13%) 6

Practical Administration Guidelines

Levetiracetam can be administered undiluted via IV push through peripheral access without requiring dilution, pumps, or carrier fluid. 4, 7, 6

• Doses up to 2500 mg over 5 minutes via peripheral IV are safe 4, 5
• Doses up to 4000 mg over 15 minutes have been studied without serious adverse events 5
• Undiluted IV push over 2-5 minutes is safe for doses up to 2000 mg 6

Safety Profile

Adverse effects are minimal and primarily CNS-related (dizziness 52.8%, somnolence 33.3%, fatigue 11.1%), with no clear relationship between adverse events and infusion rate or dose level. 5

• No serious adverse events documented with rapid infusion rates 2, 4, 8, 6
• Safety profiles are similar whether administered over 5 or 15 minutes 5
• Particularly safe in elderly patients with vascular status epilepticus 8

Maintenance Dosing After Loading

Following the loading dose, continue with 30 mg/kg IV every 12 hours (maximum 1500 mg per dose) for convulsive status epilepticus. 1

• For non-convulsive status epilepticus, use 15 mg/kg (maximum 1500 mg) IV every 12 hours 1
• Alternative maintenance: 500-1500 mg every 12 hours based on clinical response 2

Renal Adjustment Considerations

Dose adjustment is necessary in patients with renal impairment based on creatinine clearance. 3

• The FDA label mandates dose adjustments for creatinine clearance abnormalities 3
• Most study populations had no significant renal dysfunction (CrCl >60 mL/min) 6

Clinical Context and Efficacy

Levetiracetam demonstrates equivalent efficacy to valproate (73% vs 68% seizure cessation) when both are dosed at 30 mg/kg, with superior cardiovascular safety compared to phenytoin. 1, 2

• Levetiracetam causes minimal hypotension (essentially 0%) compared to phenytoin (12%) 1
• Does not require cardiac monitoring during administration 1
• Particularly effective in elderly patients with vascular etiology 8
• Less effective in cryptogenic status epilepticus, primarily generalized status epilepticus, and brain anoxia cases 8