Levetiracetam Dosing Information
Status Epilepticus (Acute Seizure Management)
For status epilepticus refractory to benzodiazepines, administer levetiracetam 30 mg/kg IV over 5 minutes as a second-line agent, with demonstrated efficacy of 68-73% for seizure control. 1
Acute IV Dosing Protocol
- Loading dose: 30 mg/kg IV administered over 5 minutes 1, 2
- Alternative studied dosing: 1500-2500 mg IV over 5 minutes in adults 2
- Do not use lower doses: 20 mg/kg shows significantly reduced efficacy (38% within 30 minutes) and is not recommended 2
- Minimal cardiovascular effects with no hypotension risk, unlike phenytoin (12% risk) or valproate 1, 3
Clinical Context for Status Epilepticus
- Levetiracetam is positioned as a second-line agent after benzodiazepines fail 1, 2
- Comparable efficacy to valproate (73% vs 68% seizure cessation when both used at 30 mg/kg) 2, 3
- No cardiac monitoring required, making it particularly suitable for elderly patients 1
- Can be administered rapidly without the cardiovascular risks associated with phenytoin/fosphenytoin 1, 3
Chronic Epilepsy Management (Oral Maintenance Therapy)
Adults (≥16 Years) - Partial Onset Seizures
Initiate treatment at 1000 mg/day (500 mg twice daily), with dose escalation by 1000 mg/day every 2 weeks to a maximum of 3000 mg/day. 4
- Starting dose: 500 mg twice daily 4
- Titration: Increase by 1000 mg/day increments every 2 weeks 4
- Target dose: 3000 mg/day (1500 mg twice daily) 4
- No evidence of additional benefit above 3000 mg/day 4
- Can be taken with or without food 4
Pediatric Patients (4 to <16 Years) - Partial Onset Seizures
Start at 20 mg/kg/day divided twice daily (10 mg/kg BID), increasing by 20 mg/kg increments every 2 weeks to target dose of 60 mg/kg/day. 4
- Initial: 10 mg/kg twice daily 4
- Target: 30 mg/kg twice daily (60 mg/kg/day total) 4
- Mean effective dose in trials: 52 mg/kg/day 4
- Weight-based formulation selection: Use oral solution for ≤20 kg; tablets or solution for >20 kg 4
Myoclonic Seizures (≥12 Years) and Primary Generalized Tonic-Clonic Seizures (≥16 Years)
Begin at 1000 mg/day (500 mg BID) and increase by 1000 mg/day every 2 weeks to the recommended dose of 3000 mg/day. 4
- Lower doses have not been adequately studied for these indications 4
- The 3000 mg/day target is evidence-based for these seizure types 4
Renal Impairment Dosing
Adjust dosing based on creatinine clearance, with reductions required for moderate to severe renal dysfunction. 4
Dosing by Renal Function
- Normal (CLcr >80 mL/min): 500-1500 mg every 12 hours 4
- Mild (CLcr 50-80 mL/min): 500-1000 mg every 12 hours 4
- Moderate (CLcr 30-50 mL/min): 250-750 mg every 12 hours 4
- Severe (CLcr <30 mL/min): 250-500 mg every 12 hours 4
- ESRD on dialysis: 500-1000 mg every 24 hours, with 250-500 mg supplemental dose after dialysis 4
Safety and Tolerability Profile
Common Adverse Effects
- CNS-related effects most common: somnolence, asthenia, headache, dizziness 1, 5, 6
- Infection risk slightly increased (OR 1.82) 7
- Behavioral changes more frequent in children <4 years, often occurring early in titration even at low doses (<20 mg/kg/day) 8
- All behavioral side effects reversible upon discontinuation 8
Key Safety Advantages
- No clinically significant drug-drug interactions with other antiepileptics, digoxin, warfarin, probenecid, or oral contraceptives 5, 9
- Not metabolized through P450 system 9
- Minimal plasma protein binding 9
- No serious idiosyncratic reactions reported 9
- Pregnancy Category C 6
Critical Monitoring
- Prepare respiratory support when combining with other sedatives 3
- Monitor oxygen saturation during administration in acute settings 3
- Behavioral monitoring essential in young children 8
Clinical Pearls
Efficacy Data
- 15% of patients on 1000 mg/day achieve ≥50% seizure reduction 7
- 20-30% of patients on 3000 mg/day achieve ≥50% seizure reduction 7
- Clear dose-response relationship demonstrated 7
- Positive effects on cognition and quality of life measures 7