What is the recommended dosage of intravenous (IV) Levetiracetam (Keppra) for a patient with seizures or epilepsy, considering factors such as renal function and severity of seizures?

Intravenous Levetiracetam Dosing

For status epilepticus, administer levetiracetam 30 mg/kg IV (maximum 2,500-3,000 mg) over 5-15 minutes as a second-line agent after benzodiazepines, with maintenance dosing of 30 mg/kg IV every 12 hours (maximum 1,500 mg per dose). 1, 2

Initial Loading Dose for Status Epilepticus

Second-line treatment after benzodiazepine failure:

• Loading dose: 30 mg/kg IV (approximately 2,000-3,000 mg for average adults) administered over 5-15 minutes 1, 2
• Maximum single dose: 2,500-3,000 mg 3, 1
• This dosing achieves 68-73% efficacy in benzodiazepine-refractory status epilepticus 1, 2

Alternative dosing studied:

• 1,500-2,500 mg IV over 5 minutes showed 83-89% seizure termination in prospective trials 2, 4
• Lower doses of 20 mg/kg show reduced efficacy (38-67%) and are not recommended as first choice 2, 4

Maintenance Dosing After Status Epilepticus Resolution

For convulsive status epilepticus:

• 30 mg/kg IV every 12 hours (maximum 1,500 mg per dose) 3, 1
• Alternative: increase prophylaxis dose by 10 mg/kg (to 20 mg/kg) IV every 12 hours 3, 1

For non-convulsive status epilepticus:

• 15 mg/kg IV every 12 hours (maximum 1,500 mg per dose) 3, 1

Standard Dosing for Chronic Epilepsy Management

When initiating therapy or switching from oral:

• Start with 1,000 mg/day given as 500 mg IV every 12 hours 5
• May increase by 1,000 mg/day every 2 weeks to maximum 3,000 mg/day 5
• The equivalent daily IV dosage should match the total daily oral dosage and frequency 5

Administration Guidelines

Infusion parameters:

• Standard FDA-approved rate: 15-minute IV infusion 5
• Rapid infusion (off-label): 5-minute infusion is safe and well-tolerated based on multiple studies showing minimal adverse effects 6, 7
• Can be administered via peripheral IV access 6
• Each 500 mg should be diluted in 100 mL normal saline for standard administration 8
• Pre-mixed bags (500 mg, 1,000 mg, or 1,500 mg) should not be further diluted 5

Renal Dose Adjustments

Critical consideration: Levetiracetam is primarily renally cleared and requires dose reduction in renal impairment 5, 9

Creatinine Clearance	Dosage	Frequency
>80 mL/min (Normal)	500-1,500 mg	Every 12 hours
50-80 mL/min (Mild)	500-1,000 mg	Every 12 hours
30-50 mL/min (Moderate)	250-750 mg	Every 12 hours
<30 mL/min (Severe)	250-500 mg	Every 12 hours
ESRD on dialysis	500-1,000 mg	Every 24 hours*

*Following dialysis, give 250-500 mg supplemental dose 5

For patients on CVVH: Consider initial dose of 1,000 mg every 12 hours with therapeutic drug monitoring, as clearance approximates normal renal function 9

Pediatric Dosing

For status epilepticus in children:

• Loading dose: 40 mg/kg IV (maximum 2,500 mg) over 5-15 minutes 3
• Maintenance for convulsive SE: 30 mg/kg IV every 12 hours (maximum 1,500 mg) 3, 1
• Maintenance for non-convulsive SE: 15 mg/kg IV every 12 hours (maximum 1,500 mg) 3, 1

Safety data supports:

• Single loading dose of 50 mg/kg (maximum 2,500 mg) over 15 minutes is well-tolerated in children 6 months to 15 years 10
• Doses up to 60 mg/kg have been evaluated with acceptable safety profiles 2, 4

Monitoring Requirements

During and immediately after infusion (0-2 hours):

• Vital signs every 15 minutes during infusion and for 2 hours post-infusion 2
• Neurological assessments every 15 minutes focusing on seizure activity or recurrence 2
• Continuous oxygen saturation monitoring 1

Extended monitoring (2-24 hours):

• Vital signs every 30 minutes for hours 2-8 2
• Hourly monitoring from 8-24 hours for delayed adverse effects 2

Safety Profile and Adverse Effects

Levetiracetam has minimal cardiovascular effects compared to other second-line agents:

• 0% hypotension risk (vs. 12% with fosphenytoin) 1
• No cardiac monitoring required during administration 1
• Minimal drug interactions 9, 8

Common mild adverse effects:

• Somnolence, fatigue, dizziness 2, 8
• Rarely: nausea, transient transaminitis 2
• In pediatrics: sleepiness, fatigue, restlessness 10

Clinical Context and Efficacy

Position in treatment algorithm:

• Second-line agent after benzodiazepines (lorazepam or midazolam) 1, 2
• Comparable efficacy to valproate (73% vs. 68% seizure cessation when both used at 30 mg/kg) 2
• Superior safety profile compared to phenytoin/fosphenytoin 1

Specific populations with enhanced efficacy:

• Elderly patients with vascular status epilepticus (89% seizure reduction) 2, 8
• Overall efficacy: 71-76.6% in benzodiazepine-refractory status epilepticus 8, 7

Critical Pitfalls to Avoid

Do not use inadequate loading doses: 20 mg/kg shows only 38-67% efficacy; use 30 mg/kg for optimal seizure control 2, 4

Do not skip renal dose adjustments: Failure to reduce doses in renal impairment leads to drug accumulation 5, 9

Do not use as monotherapy for active seizures: Always administer benzodiazepines first; levetiracetam is a second-line agent 1, 2

Avoid abrupt discontinuation: Taper gradually to reduce risk of increased seizure frequency and status epilepticus 5