What is the recommended IV dose of Levetiracetam (Keppra) for a patient with seizures, considering factors such as weight, age, and renal function?

Levetiracetam IV Dosing

For status epilepticus, administer levetiracetam 30 mg/kg IV (maximum 3000 mg) over 5-15 minutes as a second-line agent after benzodiazepines, followed by maintenance dosing of 500-1500 mg every 12 hours. 1, 2

Status Epilepticus Dosing (Second-Line After Benzodiazepines)

Loading Dose:

• 30 mg/kg IV (maximum 3000 mg) over 5-15 minutes 1, 2
• Can be administered as rapid IV push over 5 minutes or as 15-minute infusion 2
• Lower doses of 20 mg/kg show significantly reduced efficacy (38-67%) and should be avoided 3, 2
• Efficacy: 68-73% seizure cessation in benzodiazepine-refractory status epilepticus 1, 2

Maintenance Dosing:

• Convulsive status epilepticus: 30 mg/kg IV every 12 hours OR 20 mg/kg IV every 12 hours (maximum 1500 mg per dose) 1, 2
• Non-convulsive status epilepticus: 15 mg/kg IV every 12 hours (maximum 1500 mg per dose) 1, 2

FDA-Approved Dosing for Chronic Seizure Management

When oral administration is temporarily not feasible, the FDA recommends 4:

Initial Dosing:

• Start with 500 mg IV twice daily 4
• Increase by 500 mg twice daily every 2 weeks 4
• Maximum recommended dose: 1500 mg twice daily (3000 mg/day total) 4
• Administer each dose over 15 minutes 4

Important: The FDA-approved dosing is for chronic seizure management when switching from oral therapy, NOT for acute status epilepticus where higher loading doses are required 4.

Pediatric Dosing

Status Epilepticus (Children):

• Loading dose: 40 mg/kg IV (maximum 2500 mg) over 5-15 minutes 1
• Maintenance: 30 mg/kg IV every 12 hours (maximum 1500 mg) for convulsive SE 1
• Maintenance: 15 mg/kg IV every 12 hours (maximum 1500 mg) for non-convulsive SE 1

Research supports that 50 mg/kg loading doses are well-tolerated in children, achieving mean levels of 83.3 mcg/mL with no serious adverse reactions 5. However, guideline recommendations favor 40 mg/kg as the standard loading dose 1.

Renal Dose Adjustments

Critical: Levetiracetam is primarily renally cleared and requires dose adjustment based on creatinine clearance 4:

Creatinine Clearance	Dosage	Frequency
>80 mL/min (Normal)	500-1500 mg	Every 12 hours
50-80 mL/min (Mild)	500-1000 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	500-1000 mg	Every 24 hours*

*Following dialysis, a 250-500 mg supplemental dose is recommended 1, 4.

For patients on CVVH, consider 1000 mg every 12 hours with therapeutic drug monitoring, as clearance approximates normal renal function 6.

Administration Guidelines

Preparation and Infusion:

• Do NOT dilute the premixed bags prior to use 4
• Available concentrations: 500 mg/100 mL, 1000 mg/100 mL, 1500 mg/100 mL 4
• Standard infusion time: 15 minutes 4
• For status epilepticus, can be given over 5 minutes without cardiac monitoring 1, 2
• Discard any unused portion 4

Compatibility:

• Compatible with lorazepam, diazepam, and valproate sodium for at least 24 hours at room temperature 4

Key Advantages Over Alternative Agents

Levetiracetam offers significant safety advantages:

• No hypotension risk (0% vs 12% with fosphenytoin) 1, 2
• No cardiac monitoring required (unlike phenytoin/fosphenytoin) 1, 2
• Minimal drug interactions 2
• Can be administered rapidly without cardiovascular toxicity 2

Monitoring Requirements

Post-Administration Monitoring:

• Vital signs and neurological assessments every 15 minutes during infusion and for 2 hours post-infusion 3
• Then every 30 minutes for hours 2-8 3
• Then hourly from 8-24 hours 3
• Monitor for somnolence, fatigue, and behavioral changes 4
• No therapeutic drug monitoring required for routine use 2

Critical Safety Considerations

Adverse Effects:

• Common: somnolence, fatigue, dizziness (CNS depression at higher doses) 2, 4
• Behavioral abnormalities: aggression, agitation, irritability, depression (13.3% vs 6.2% placebo) 4
• Serious dermatological reactions: discontinue at first sign of rash 4
• DRESS syndrome: discontinue if suspected 4

Contraindications:

• Known hypersensitivity to levetiracetam 4
• Anaphylaxis and angioedema have been reported 4

Withdrawal:

• Avoid abrupt discontinuation to reduce risk of increased seizure frequency and status epilepticus 4
• Taper gradually when discontinuing 4

Common Pitfalls to Avoid

1. Do not use 20 mg/kg loading doses for status epilepticus—efficacy drops to 38-67% compared to 68-73% with 30 mg/kg 3, 2
2. Do not forget renal dose adjustments—levetiracetam is primarily renally cleared 4, 6
3. Do not confuse FDA chronic dosing (500 mg twice daily starting dose) with acute status epilepticus dosing (30 mg/kg loading dose) 1, 2, 4
4. Do not dilute premixed bags—they are ready to use 4
5. Do not skip supplemental dosing after dialysis—give 250-500 mg post-dialysis 1, 4