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Efficacy, tolerability, and kinetics of lamotrigine in infants
Mohamad A Mikati1, Michel Fayad, Majed Koleilat
1Department of Pediatrics, Adult and Pediatric Epilepsy Program, American University of Beirut, New York City, New York 10022, USA.
Insights
Lamotrigine effectively treats partial seizures and infantile spasms in infants under one year old. Its use requires consideration of age-dependent pharmacokinetic changes in neonates and young infants.
Area of Science:
- Pediatric Neurology
- Clinical Pharmacology
Background:
- Intractable seizures in infants present significant treatment challenges.
- Lamotrigine is an established antiepileptic drug, but its use in neonates and infants requires careful dosing due to potential pharmacokinetic differences.
Purpose of the Study:
- To evaluate the efficacy, tolerability, and pharmacokinetic profile of lamotrigine in infants during their first year of life.
- To compare lamotrigine's effectiveness and safety in infants with older children.
Main Methods:
- An open-label study involving 13 infants with intractable seizures (partial seizures and/or infantile spasms).
- Lamotrigine was administered as add-on therapy for 3 months, with seizure frequency, response ratio, and side effect scores assessed.
- Pharmacokinetic parameters, including apparent clearance and half-life, were analyzed, with a focus on age-dependent changes.
Main Results:
- Significant reductions in daily seizure rates for both partial seizures (P=.027) and infantile spasms (P=.028) were observed.
- Apparent clearance of lamotrigine increased significantly with age, showing a breakpoint at 2 months (P <.001).
- Neonates (<2 months) exhibited a longer half-life (23.44 ± 3.57 hours), while efficacy and adverse effect profiles were comparable to older children.
Conclusions:
- Lamotrigine is a well-tolerated and effective treatment for partial seizures and infantile spasms in infants under one year of age.
- Age-dependent pharmacokinetics of lamotrigine, particularly in the first two months of life, necessitate individualized dosing strategies.
- Further consideration of these age-specific kinetic profiles is crucial for optimizing lamotrigine therapy in pediatric populations.
Objectives:
To investigate the efficacy, tolerability, and kinetics of lamotrigine during the first year of life.
Study Design:
We studied 13 infants with intractable seizures; 7 had partial seizures and 7 had infantile spasms (1 had both). Patients received open-label lamotrigine as add-on therapy for 3 months. Seizure frequency, response ratio, and side effects score were determined and compared with the baseline period.
Results:
The rate of partial seizures per day decreased from 8.57 +/- 2.29 to 4.00 +/- 2.15 (P =.027) and infantile spasms from 8.71 +/- 2.15 to 3.61 +/- 2.762 (P =.028). Apparent clearance increased during the first year of life, with a break point at 2 months of age (mean, 0.119 +/- 0.021, 0.217 +/- 0.094 L/h per kilogram for infants <2 months and those 2 to 12 months old, respectively,P <.001). Twenty-four-hour concentration to time plots of three 3- to 4-week-old neonates showed a half-life of 23.44 +/- 3.57 hours. Compared with a group of 17 older children, LTG had similar efficacy (response ratios, -0.68 +/- 0.12 and -0.74 +/- 0.11, P =.504), and similar adverse effects scores (0.67 +/- 0.67 and 0.23 +/- 0.166, P =.95).
Conclusions:
Lamotrigine is a useful and well tolerated drug for partial seizures and infantile spasms in infants <1 year of age. However, lamotrigine has age-dependent kinetics that must be taken into consideration.