What are the loading and maintenance doses of Levetiracetam (Levipil) in pediatric patients?

Levetiracetam (Levipil) Dosing in Pediatrics

For pediatric patients, initiate levetiracetam at 20 mg/kg/day divided into two doses (10 mg/kg BID), then increase by 20 mg/kg every 2 weeks to the recommended maintenance dose of 60 mg/kg/day (30 mg/kg BID). 1

Loading Dose for Acute Seizure Management

For status epilepticus in children, use a loading dose of 40-60 mg/kg IV (maximum 2,500 mg) as a bolus. 2

• Pediatric data demonstrates safety across loading doses of 20,40, and 60 mg/kg IV, with no significant blood pressure changes, local infusion site reactions, or ECG abnormalities 3
• For convulsive status epilepticus, the American Academy of Neurology recommends 40 mg/kg IV bolus (maximum 2,500 mg) with moderate strength of evidence 2
• For non-convulsive status epilepticus, the same 40 mg/kg IV bolus (maximum 2,500 mg) is recommended 2
• Higher loading doses up to 60 mg/kg have been used safely in pediatric patients 3, 2

Maintenance Dosing by Age and Indication

Partial Onset Seizures (Ages 4-16 Years)

Start at 20 mg/kg/day in 2 divided doses (10 mg/kg BID), increase every 2 weeks by 20 mg/kg increments to reach 60 mg/kg/day (30 mg/kg BID). 1

• If the patient cannot tolerate 60 mg/kg/day, the dose may be reduced 1
• In clinical trials, the mean daily dose was 52 mg/kg 1
• Children ≤20 kg should receive oral solution; those >20 kg can use either tablets or oral solution 1

Weight-based dosing for tablets: 1

• 20.1-40 kg patients:
  • Starting (20 mg/kg/day): 250 mg BID
  • Intermediate (40 mg/kg/day): 500 mg BID
  • Target (60 mg/kg/day): 750 mg BID
• >40 kg patients:
  • Starting (20 mg/kg/day): 500 mg BID
  • Intermediate (40 mg/kg/day): 1000 mg BID (two 500 mg tablets BID)
  • Target (60 mg/kg/day): 1500 mg BID (two 750 mg tablets BID)

Primary Generalized Tonic-Clonic Seizures (Ages 6-16 Years)

Use the same dosing regimen: start at 20 mg/kg/day in 2 divided doses, increase by 20 mg/kg every 2 weeks to 60 mg/kg/day. 1

• Doses lower than 60 mg/kg/day have not been adequately studied for efficacy in this indication 1

Myoclonic Seizures (Ages 12 Years and Older)

Start at 1000 mg/day in 2 divided doses (500 mg BID), increase by 1000 mg/day every 2 weeks to 3000 mg/day. 1

• Doses lower than 3000 mg/day have not been studied for this indication 1

Clinical Efficacy Data

In open-label pediatric studies, 52% of children achieved >50% seizure reduction at 20-40 mg/kg/day maintenance dosing. 4

• A multicenter study showed 51.5% of children had >50% seizure reduction at 26 weeks on a median dose of 22 mg/kg/day 5
• Retention rate was 69.7% after 26 weeks 5
• Levetiracetam was effective in both partial and primary generalized seizures, with greatest effect in partial seizures 5
• Two children remained seizure-free during the entire evaluation period in one trial 4

Pharmacokinetic Considerations

Children require 30-40% higher weight-normalized doses than adults due to increased clearance. 6

• Apparent body clearance in children (1.43 ± 0.36 ml/min/kg) is 30-40% higher than in adults 6
• Half-life in children is 6.0 ± 1.1 hours for levetiracetam 6
• Renal clearance is higher in children compared to adults 6

Special Situations

Seizure Prophylaxis (e.g., CAR T-cell therapy)

Use 10 mg/kg (maximum 500 mg per dose) every 12 hours for 30 days. 3

• This dosing is specifically for prevention, not treatment of active seizures 3

Busulfan-Induced Seizure Prevention

Start 10 mg/kg twice daily (20 mg/kg/day in 2 divided doses) 6-24 hours before busulfan initiation, continue until 24-48 hours after the last busulfan dose. 7

• Both oral and IV routes are effective 7
• No loading dose is used for this indication 7

Safety Profile and Adverse Effects

Levetiracetam is generally well tolerated in children, with most adverse effects being mild and CNS-related. 5, 4

• Most common adverse effects: hyperactivity (48.5%), somnolence (36.4%), irritability (33.3%), and aggressive behavior (27.3%) 5
• Other reported effects include headache, infection, and anorexia 4
• In oral loading studies, 89% of patients denied adverse effects 3
• Serious adverse events are rare and typically unrelated to levetiracetam use 5

Critical Pitfalls to Avoid

Do not use household teaspoons or tablespoons for oral solution—always use a calibrated measuring device. 1

• Only whole tablets should be administered; do not split tablets 1
• Do not exceed 60 mg/kg/day for chronic maintenance therapy without clear clinical justification 1
• For status epilepticus, do not use maintenance dosing—a loading dose is required 2
• Levetiracetam does not interact with other antiepileptic drugs, so no dose adjustments of concomitant AEDs are needed 4

Route of Administration

Levetiracetam can be given orally or intravenously with or without food. 1

• IV and oral routes have equivalent bioavailability and tolerability 8
• For acute seizures, IV administration is preferred for rapid therapeutic levels 3