Epileptic child in remission: Ceiling effect of valproic acid
Mariem Kammoun1, Rim Charfi1, Abir Boussetta2
1University of Tunis El Manar, Faculty of Medicine of Tunis, 1007, National Center of Pharmacovigilance Chalbi Belkahia, Department of Clinical Pharmacology, LR16SP02, 1006, Tunis, Tunisia.
Insights
Therapeutic drug monitoring for valproic acid in epileptic children found a ceiling dose of 44.44 mg/kg/day for remission. Lower doses were effective in children with epilepsy in remission, indicating optimized treatment potential.
Area of Science:
- Pediatric Neurology
- Clinical Pharmacology
- Epileptology
Background:
- Therapeutic drug monitoring (TDM) of valproic acid (VPA) is crucial for optimizing epilepsy treatment in children.
- TDM aims to improve seizure control and identify refractory cases early.
- Establishing optimal VPA dosing is essential for effective pediatric epilepsy management.
Purpose of the Study:
- To determine a ceiling dose for valproic acid (VPA) in epileptic children.
- To identify the trough serum level of VPA associated with remission in pediatric epilepsy.
- To optimize VPA treatment strategies for improved seizure control.
Main Methods:
- Retrospective study of epileptic children aged 2-18 years.
- Inclusion of patients with at least two VPA trough level measurements over 13 years (2009-2022).
- Analysis of VPA dosage, serum levels, remission status, and adverse events.
Main Results:
- 88 children were analyzed; 67% achieved remission.
- Mean VPA dose was lower in the remission group (21.53 mg/kg/day) compared to the non-remission group (26.81 mg/kg/day).
- A ceiling dose of 44.44 mg/kg/day was identified as limiting treatment efficacy for achieving remission.
Conclusions:
- The average weight-based VPA dose in children with epilepsy in remission was lower than in those not meeting remission criteria.
- A ceiling dose of 44.44 mg/kg/day for VPA was identified, suggesting a limit to treatment efficacy for achieving remission.
- These findings support the need for individualized VPA dosing strategies in pediatric epilepsy.
Introduction:
Therapeutic drug monitoring (TDM) of valproic acid (VPA) for epileptic children aims to optimize treatment, hence promoting seizure control, and to detect refractory cases that should be managed early. We aimed to identify a ceiling dose and a trough serum level of VPA in epileptic children in remission.
Methods:
This retrospective study was carried out at Clinical Pharmacology, involving epileptic children (2-18 years) who were referred at least two times for a VPA trough level measurement over a 13-year period (2009-2022).
Results:
We included 88 children, of whom 67% (n=59) were in remission (G1) and 33% (n=29) did not meet remission criteria (G2). Ten children (11%) experienced adverse events, predominantly gastrointestinal and neuropsychological disturbances. Mean weight-based dose of VPA in G1 (21.53±7.95 mg/kg/day) was significantly lower than in G2 (26.81±9.99 mg/kg/day), p=0.009. Mean VPA trough serum level was 60.76±20.22 µg/mL in G1 and 62.47±23.04 µg/mL in G2 with no significant difference. The ceiling daily dose of VPA to achieve remission was 44.44 mg/kg/day.
Conclusion:
Our study showed that the average weight-based dose of VPA in children in remission was lower than that in G2. A ceiling dose of 44.44 mg/kg/day of VPA limiting treatment efficacy for achieving remission was identified.
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