Loading Dose of Keppra (Levetiracetam)
For adults with normal renal function and body weight ≥50 kg, administer 1,500 mg of levetiracetam as a single oral or IV loading dose, or use 30-60 mg/kg IV (maximum 4,500 mg) at 100 mg/min for status epilepticus. 1, 2
Standard Loading Dose for Seizure Management
- For resuming antiepileptic therapy in the emergency department: A 1,500 mg oral or IV loading dose is well-established, safe, and achieves therapeutic levels rapidly without significant adverse effects 1, 2
- Serum concentrations achieved: After a 1,500 mg oral load, mean concentrations reach approximately 31.5 mcg/mL at 1 hour and 30.77 mcg/mL at 2 hours in patients weighing around 85 kg 3
- Maintenance dosing: Begin 12 hours after loading with 500-1,000 mg twice daily 1, 3
Status Epilepticus Loading Doses
Adults
- Second-line agent after benzodiazepines: Administer 30-60 mg/kg IV (maximum 4,500 mg) at a rate of 100 mg/min 2
- Alternative dosing from clinical trials: 2,500 mg IV over 5-15 minutes has been studied, though weight-based dosing is preferred 1
- Key advantages: No cardiac monitoring required, minimal drug interactions, and can be given rapidly without dilution concerns 2
Pediatrics
- For convulsive status epilepticus: 40 mg/kg IV bolus (maximum 2,500 mg) in addition to benzodiazepines 1, 2
- For non-convulsive status epilepticus: Same 40 mg/kg IV bolus (maximum 2,500 mg) 1
- Maintenance after loading: 15 mg/kg IV every 12 hours or increase prophylaxis dose by 10 mg/kg (to 20 mg/kg) every 12 hours (maximum 1,500 mg) 1
Route of Administration
- Oral and IV formulations are bioequivalent: Both achieve rapid therapeutic levels, with oral bioavailability >95% 1, 4
- IV infusion rate: Can be administered at 100 mg/min for status epilepticus, or rapid undiluted IV push is safe 1, 2
- Food effects: Co-ingestion slows absorption rate but not extent, so can be given with or without food 4
Special Populations
Renal Impairment
- Creatinine clearance <30 mL/min: Reduce loading dose or avoid; if used, consider 1 mg/kg/hour for status epilepticus 1
- Creatinine clearance 30-60 mL/min: Use caution and consider dose reduction 1
- Dialysis patients: Levetiracetam is cleared by dialysis; supplemental dosing after dialysis may be needed 1
Critically Ill Patients
- Augmented renal clearance: At least 1,500 mg twice daily is recommended, with careful monitoring of creatinine clearance 2
Elderly Patients
- Elimination half-life is prolonged: 10-11 hours in elderly volunteers compared to 6-8 hours in younger adults, suggesting potential need for dose adjustment 4
Prophylactic Loading (Non-Acute Settings)
- CAR T-cell therapy seizure prophylaxis: 500-750 mg orally every 12 hours for 30 days starting on day of infusion (no loading dose) 2
- Brain tumor patients during radiotherapy: Doses of 30-50 mg/kg/day (500-2,500 mg) in single or divided doses, adjusted based on clinical response 5
Safety and Tolerability
- Adverse effects from loading: In a study of 37 patients receiving 1,500 mg oral loading, 89% denied side effects; 11% reported transient irritability, imbalance, tiredness, or lightheadedness 3
- Common adverse effects with maintenance: Fatigue, dizziness, rarely pain at infusion site 1
- No withdrawal phenomena: Cross-titration or down-titration does not cause typical withdrawal-related adverse events or rebound seizures 6
Clinical Pitfalls to Avoid
- Underdosing in status epilepticus: Use full weight-based loading doses (40 mg/kg in pediatrics, 30-60 mg/kg in adults) rather than fixed lower doses 2
- Delaying administration: Rapid undiluted IV push is safe; do not delay for dilution concerns 2
- Assuming therapeutic drug monitoring is needed: Unlike phenytoin or valproate, levetiracetam does not require routine level monitoring in most patients 2, 7
- Overlooking renal function: Clearance is directly dependent on creatinine clearance; always assess renal function before loading 4