What are the weight‑based dosing recommendations for Keppra (levetiracetam) in children and the standard dosing in adults, including adjustments for impaired renal function?

Keppra (Levetiracetam) Weight-Based Dosing

For children aged 4-16 years with partial-onset seizures, start levetiracetam at 20 mg/kg/day divided twice daily (10 mg/kg BID), increasing by 20 mg/kg increments every 2 weeks to a target of 60 mg/kg/day (30 mg/kg BID); adults should receive 1000 mg/day (500 mg BID) initially, increasing by 1000 mg/day every 2 weeks to a maximum of 3000 mg/day, with dose reductions required for creatinine clearance <80 mL/min. 1

Pediatric Dosing (Ages 4 to <16 Years)

Initial and Maintenance Dosing

• Starting dose: 20 mg/kg/day divided into two doses (10 mg/kg BID) 1
• Titration schedule: Increase by 20 mg/kg every 2 weeks 1
• Target maintenance dose: 60 mg/kg/day (30 mg/kg BID) 1
• If intolerance occurs: The daily dose may be reduced below 60 mg/kg/day; mean effective dose in clinical trials was 52 mg/kg/day 1

Weight-Based Administration Guidelines

• Children ≤20 kg: Must use oral solution formulation 1
• Children >20 kg: May use either tablets or oral solution 1
• Children 20.1-40 kg at target dose: 1500 mg/day (one 750 mg tablet BID) 1
• Children >40 kg at target dose: 3000 mg/day (two 750 mg tablets BID) 1

Pharmacokinetic Considerations in Children

• Children demonstrate 30-40% higher apparent body clearance compared to adults (1.43 ± 0.36 mL/min/kg), necessitating weight-based dosing adjustments 2
• Population pharmacokinetic modeling confirms that a 10 mg/kg BID regimen in children achieves plasma concentrations equivalent to the adult starting dose of 500 mg BID 3, 4
• Body weight is the most influential covariate affecting levetiracetam pharmacokinetics in pediatric patients 4

Adult Dosing (≥16 Years)

Partial-Onset Seizures

• Starting dose: 1000 mg/day divided twice daily (500 mg BID) 1
• Titration schedule: May increase by 1000 mg/day every 2 weeks 1
• Maximum recommended dose: 3000 mg/day 1
• Important caveat: Doses >3000 mg/day have been studied in open-label trials but show no evidence of additional benefit 1

Myoclonic Seizures (≥12 Years) and Primary Generalized Tonic-Clonic Seizures (≥16 Years)

• Starting dose: 1000 mg/day (500 mg BID) 1
• Target dose: 3000 mg/day, increased by 1000 mg/day every 2 weeks 1
• Critical note: Effectiveness of doses <3000 mg/day has not been adequately studied for these indications 1

Renal Impairment Dosing Adjustments

Adult Patients with Impaired Renal Function

Levetiracetam is 70% renally excreted unchanged, making dose adjustment essential based on creatinine clearance 5, 6

Dosing by Creatinine Clearance (CLcr):

• Normal (>80 mL/min): 500-1500 mg every 12 hours 1
• Mild impairment (50-80 mL/min): 500-1000 mg every 12 hours 1
• Moderate impairment (30-50 mL/min): 250-750 mg every 12 hours 1
• Severe impairment (<30 mL/min): 250-500 mg every 12 hours 1
• End-stage renal disease on dialysis: 500-1000 mg every 24 hours, with a 250-500 mg supplemental dose following dialysis 1

Calculating Creatinine Clearance

Use the Cockcroft-Gault equation: CLcr = [140 - age (years)] × weight (kg) × (0.85 for females) / [72 × serum creatinine (mg/dL)] 1

Special Consideration: Augmented Renal Clearance (ARC)

• Critically ill patients with ARC: The standard starting dose of 500 mg BID is inadequate; levetiracetam clearance can reach 6.5 L/h (versus 3.8 L/h in healthy individuals) 6
• Recommended dose for ARC patients: At least 1500 mg BID to achieve therapeutic exposures comparable to non-ARC patients receiving 1000 mg BID 6
• ARC prevalence: Ranges from 30-90% in critically ill populations 6

Administration and Monitoring

Route and Timing

• May be administered with or without food 1
• For oral solution in pediatrics: Use a calibrated measuring device, not household spoons 1
• Only whole tablets should be administered; do not split 1

Seizure Prophylaxis in Special Populations

• Patients with CNS disease or seizure history receiving CAR T-cell therapy: Administer levetiracetam 10 mg/kg (maximum 500 mg per dose) every 12 hours for 30 days following infusion 7
• This prophylactic regimen is well-tolerated with minimal drug interactions and does not affect cytokine levels 7

Common Pitfalls and Caveats

Dosing Errors to Avoid

• Do not use adult fixed dosing in children <40 kg: This results in subtherapeutic concentrations due to higher weight-normalized clearance 2, 3
• Do not overlook renal function changes: Even mild renal impairment (CLcr 50-80 mL/min) requires dose reduction 1
• Do not assume standard dosing in critically ill patients: ARC significantly increases clearance, necessitating higher doses 6

Monitoring Considerations

• Renal function: Monitor creatinine clearance, especially in elderly patients, those with renal disease, and critically ill patients 1, 6
• Therapeutic drug monitoring: While not routinely required, may be useful in patients with renal dysfunction, suspected non-adherence, or suboptimal seizure control 5
• Target trough concentrations: 6-20 mg/L has been described, though the relationship between plasma concentrations and clinical effect requires further validation in children 3

Drug Interactions

• Enzyme-inducing antiepileptic drugs: Increase levetiracetam clearance, though the clinical significance is modest compared to renal function and body weight 4
• No significant interactions: Levetiracetam has minimal drug-drug interactions, making it advantageous in polypharmacy situations 6