Levetiracetam Dosing for 16-Year-Old with Cerebral Palsy and GTCS
For this 16-year-old patient weighing 20-30 kg presenting with generalized tonic-clonic seizures, start levetiracetam at 20 mg/kg/day divided into two doses (10 mg/kg twice daily), which translates to 200-300 mg twice daily based on their weight, then titrate by 20 mg/kg/day every 2 weeks to a target of 60 mg/kg/day (600-900 mg twice daily). 1
Weight-Based Dosing Algorithm
For patients weighing 20-30 kg with primary generalized tonic-clonic seizures:
Starting dose: 20 mg/kg/day in 2 divided doses (10 mg/kg BID)
- For 20 kg patient: 200 mg BID (400 mg/day total)
- For 30 kg patient: 300 mg BID (600 mg/day total) 1
Titration schedule: Increase by 20 mg/kg/day every 2 weeks 1
Target maintenance dose: 60 mg/kg/day (30 mg/kg BID)
- For 20 kg patient: 600 mg BID (1200 mg/day total)
- For 30 kg patient: 900 mg BID (1800 mg/day total) 1
Evidence Supporting This Approach
The FDA label specifically addresses pediatric patients ages 6 to <16 years with primary generalized tonic-clonic seizures, stating that treatment should be initiated at 20 mg/kg/day in 2 divided doses and increased every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg. 1 The effectiveness of doses lower than 60 mg/kg/day has not been adequately studied in this population. 1
Population pharmacokinetic studies in children demonstrate that a 10 mg/kg twice daily regimen provides plasma concentrations similar to the adult starting dose of 500 mg twice daily, and that 20 mg/kg twice daily achieves the therapeutic target range of 6-20 mg/L for trough concentrations. 2 Clinical experience confirms that dosages between 12-62 mg/kg/day (median 33 mg/kg/day) are effective, with a median seizure reduction of 60% overall. 3
Formulation Considerations
For patients weighing ≤20 kg, use oral solution exclusively. 1 For patients weighing >20 kg (which includes the upper range of this patient at 30 kg), either tablets or oral solution can be used. 1
- Oral solution calculation: Total daily dose (mL/day) = [Daily dose (mg/kg/day) × patient weight (kg)] / 100 mg/mL 1
- Use a calibrated measuring device, not household spoons 1
Efficacy Data in This Population
A placebo-controlled trial in patients with idiopathic generalized epilepsy (ages 4-65 years) demonstrated that levetiracetam at target doses of 60 mg/kg/day for children produced a 56.5% mean reduction in GTC seizure frequency versus 28.2% for placebo (p=0.004). 4 Importantly, 72.2% of levetiracetam patients achieved ≥50% seizure reduction compared to 45.2% on placebo (p<0.001), and 34.2% became completely free of GTC seizures versus 10.7% on placebo (p<0.001). 4
Long-term follow-up data shows that 62.5% of patients with tonic-clonic seizures achieved ≥6 months of seizure freedom on adjunctive levetiracetam at individualized doses (20-80 mg/kg/day for children/adolescents <50 kg). 5
Safety Profile
Levetiracetam was well tolerated in pediatric trials, with only 1.3% discontinuing due to adverse events. 4 The most common side effects are tiredness (7.8%) and aggressiveness (5%), which are dose-related but rarely require discontinuation. 3 Notably, 25% of children showed positive effects on behavior and alertness. 3
Critical Caveat for Acute Seizures
If this patient is presenting with active status epilepticus rather than chronic seizure management, the dosing strategy differs completely. For benzodiazepine-refractory status epilepticus, guidelines recommend a loading dose of 30 mg/kg IV (600-900 mg for this patient) administered at 5 mg/kg/minute. 6 However, recent evidence suggests that loading doses >40 mg/kg are associated with higher intubation rates (45.8%) without improved seizure termination, so doses of 20-40 mg/kg may be safer. 7