What is the maximum recommended dose of Trileptal (oxcarbazepine) in pediatric patients?

Maximum Dose of Trileptal (Oxcarbazepine) in Pediatric Patients

The maximum recommended dose of oxcarbazepine in pediatric patients depends on age and weight: for children aged 2 to <4 years, the absolute maximum is 60 mg/kg/day given twice daily; for children aged 4 to 16 years, the maximum is 1,800 mg/day (for children >39 kg) during adjunctive therapy, or up to 2,100 mg/day during monotherapy for children weighing ≥60 kg. 1

Age-Specific Maximum Dosing

Children Aged 2 to <4 Years

• The maximum maintenance dose is 60 mg/kg/day administered in a twice-daily regimen. 1
• In clinical trials for this age group, 50% of patients reached a final dose of at least 55 mg/kg/day, demonstrating that the 60 mg/kg/day ceiling is an absolute maximum rather than a typical target. 1
• Children in this age range may require up to twice the oxcarbazepine dose per body weight compared to adults due to higher apparent clearance when normalized by body weight. 1

Children Aged 4 to 16 Years (Adjunctive Therapy)

• Maximum doses are weight-based and should not exceed: 1
  • 900 mg/day for children weighing 20–29 kg
  • 1,200 mg/day for children weighing 29.1–39 kg
  • 1,800 mg/day for children weighing >39 kg
• The median daily dose achieved in clinical trials was 31 mg/kg with a range of 6–51 mg/kg. 1
• Children aged 4 to ≤12 years may require a 50% higher oxcarbazepine dose per body weight compared to adults. 1

Children Aged 4 to 16 Years (Monotherapy)

• The maximum recommended daily dose during monotherapy ranges from 600 mg/day to 2,100 mg/day depending on body weight (see Table 1 in FDA labeling). 1
• For children weighing ≥60 kg, the maximum is 2,100 mg/day. 1

Important Dosing Considerations

Drug Interactions Requiring Dose Adjustment

• Concomitant enzyme-inducing antiepileptic drugs (EIAEDs) such as phenytoin, carbamazepine, or phenobarbital increase the clearance of oxcarbazepine's active metabolite (MHD) by approximately 29%. 2
• Children weighing 10 kg who are taking EIAEDs may require doses as high as 90 mg/kg/day to maintain therapeutic trough concentrations—exceeding the FDA's recommended maximum of 60 mg/kg/day for children aged 2 to <4 years. 2
• Dosage adjustment is recommended when oxcarbazepine is used with strong CYP3A4 or UGT enzyme inducers. 1

Renal Impairment

• In patients with creatinine clearance <30 mL/min, initiate oxcarbazepine at one-half the usual starting dose (300 mg/day in adults; proportionally reduced in children) and titrate slowly. 1

Clinical Trial Data Supporting Maximum Doses

• A multicenter trial in 254 children (mean age 9.3 years) demonstrated that the mean effective dose was 902.4 mg/day (less than 30 mg/kg/day), with daily doses not exceeding 600 mg in most cases, yet 91.1% of patients had a positive response. 3
• In very young children (≤4 years), doses ranged from 14–71 mg/kg/day (mean 36.5 mg/kg/day), with 70% experiencing significant seizure reduction and 50% becoming seizure-free. 4
• Population pharmacokinetic modeling suggests that 50-kg children without EIAEDs may need only 20–30 mg/kg/day (lower than the recommended 30–45 mg/kg/day target) to achieve therapeutic trough concentrations. 2

Common Pitfalls to Avoid

• Do not exceed 60 mg/kg/day in children aged 2 to <4 years unless under exceptional circumstances with therapeutic drug monitoring, as this is the absolute FDA-approved maximum. 1
• Do not use adult maximum doses (2,400 mg/day) in children weighing <60 kg; weight-based maximums apply. 1
• Do not forget to adjust doses downward when discontinuing concomitant enzyme-inducing AEDs, as oxcarbazepine clearance will decrease and toxicity may occur. 2
• Monitor serum sodium if the patient is taking diuretics, oral contraceptives, or NSAIDs, as hyponatremia develops in approximately 3% of patients during the first months of therapy. 5