The FDA changed the label for oxcarbazepine based on PTN research that addressed dosing information in pediatric patients with obesity to treat status epilepticus.
A population PK analysis of oxcarbazepine was conducted that included n = 92 obese and non-obese pediatric patients < 18 years of age to evaluate the potential impact of obesity on plasma oxcarbazepine exposures. Obesity was defined as BMI ≥ 95th percentile for age and sex based on CDC 2000 growth chart recommendations. Simulated results from this analysis suggested that the target maintenance doses for oxcarbazepine, applied in pediatric patients ≥ 2 years of age, produced equivalent steady-state exposure of MHD between pediatric patients with and without obesity. This finding is consistent when using total body weight, or when using fat-free mass in patients ≥ 3 years and total body weight in patients < 3 years in the simulations.
PTN clinical research showed that dosage adjustment according to obesity status is not necessary. This work helped pediatric neurologists to know the best dose of this drug for treating seizures in all pediatric patients, regardless of their obesity status.
The FDA changed the label for levetiracetam based on PTN research that addressed dosing information in pediatric patients with obesity. The PK analysis included 164 obese and non-obese participants between the ages of 2 and 18 years being treated for seizures. Results from the study provided information on how children with obesity processed the levetiracetam differently from children without obesity. The updated levetiracetam label includes this valuable information for clinicians to keep in mind as they prescribe the drug for individual patients. PTN research showed how the drug could be safely used to treat seizures in children with obesity.
A population PK analysis of topiramate was conducted in 129 children < 21 years of age with and without obesity to evaluate the potential impact of obesity on plasma topiramate exposures. Obesity was defined as BMI ≥ 95 percentile for age and sex based on CDC-recommended BMI-for-age growth charts for males and females. Using the currently recommended dosing regimens, children with obesity are likely to have median values of average concentration at steady-state and trough concentration at steady-state that are up to 20% lower and 19% lower, respectively, compared to children without obesity. Dosage adjustment according to obesity status is not necessary.
Childhood obesity has increased over the last decade. Due to altered pharmacokinetics (PK) associated with obesity, dosing for anti-epileptics in obese children may vary from that in non-obese children. Inappropriate dosing may increase the risk for drug toxicity or therapeutic failure. PK studies are urgently needed to determine appropriate dosing strategies for anti-epileptics in obese children.
The Pharmacokinetics of Anti-epileptic Drugs in Obese Children (AED) study will enroll approximately 100 children, 2 to < 18 years of age, with a body mass index (BMI) > 95th percentile, who are receiving levetiracetam, valproic acid, topiramate, or oxcarbazepine, per standard of care.
Publications
- Physiologically Based Pharmacokinetic Modeling to Characterize the Disposition of Topiramate in Children with and without ObesityJournal of Clinical Pharmacology, October 2026 Access article on PubMed
- Population Pharmacokinetic Modeling of Oxcarbazepine and Its Active Metabolite 10-Monohydroxy Derivative to Inform Dosing in Children with ObesityClinical Pharmacokinetics • November 2025 Access article on PubMed. Sinha J, Zimmerman K, Balevic SJ, Hornik C, Muller WJ, Rathore M, Meyer M, Finkelstein Y, Al-Uzri A, Lakhotia A, Goldstein S, Chen JY, Anand R, Gonzalez D; Best Pharmaceuticals for Children Act–Pediatric Trials Network Steering Committee. Oxcarbazepine (OXZ) is an antiepileptic drug whose pharmacological effect is primarily mediated ...
- Pharmacokinetics and Proposed Dosing of Levetiracetam in Children With ObesityThe Journal of Pediatric Pharmacology and Therapeutics • December 2023 Access article on PubMed. Zimmerman KO, Wu H, Maharaj A, Turner A, Chen L, Hornik CD, Arnold S, Muller W, Al-Uzri A, Meyer M, Shiloh-Malawsky Y, Taravath S, Lakhotia A, Joshi C, Jackman J, Hornik CP; on behalf of the Best Pharmaceuticals for Children Act – Pediatric ...
Status: Analysis
ClinicalTrials.gov identifier:
NCT02993861
NICHD Data and Specimen Hub (DASH):
Levetiracetam - Anti-epileptic Drugs in Obese Children
For questions about this study:
Contact the PTN.