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Key words: Adolescents - Conversion - Epilepsy - Lamotrigine - Monotherapy - Valproate
ABSTRACT
Background: Pharmacokinetic interactions can make necessary anti-epileptic medication (AED) changes hazardous for children with epilepsy. We report the utility of a dosing algorithm designed to maintain stable trough lamotrigine (LTG) concentrations during conversion from valproate (VPA) to LTG monotherapy in adolescents aged 16-20 years.
Methods: Patients were enrolled into the study if they required a change in their AED regimen due to lack of efficacy or intolerable side effects. Conversion to LTG monotherapy took place in a four part treatment algorithm. Lamotrigine was escalated according to a target dose of 200 mg/ day over 8-weeks. Valproate was withdrawn over a period of 2-6 weeks, depending on the initial dose. Lamotrigine dose was further escalated to 500 mg/day and continued for four weeks as monotherapy. Trough serum concentrations of LTG were measured during each phase of the trial.
Results: Twelve of 16 patients completed the study. After the LTG escalation to 200 mg/day, mean trough serum concentrations of 8.0pg/mL did not differ significantly from the 9.5pg/mL after VPA withdrawal or the 9.2 gg/mL after 4 weeks of monotherapy at 500 mg/day. Adverse events led to premature discontinuation for one subject. Two subjects withdrew due to worsening seizures during LTG monotherapy possibly due to non-compliance. Limitations of the trial include the open label design and small sample size of the sub-analysis.
Conclusion: In adolescent patients, this algorithm produces stable LTG serum concentrations with favorable tolerability during a transition from VPA to LTG monotherapy.
Introduction
A major challenge in the management of children with epilepsy is the conversion from one anti-epileptic drug (AED) to another to achieve better seizure control or avoid certain side effects. Given the presence of pharmacokinetic interactions between commonly used AEDs, such switches involve a risk of increased side effects and seizures. While these problems may be transient during a conversion, it does not make them any less dangerous or less discouraging to the children and their families. This is especially a problem in the transition from valproic acid (VPA) monotherapy to lamotrigine (LTG) monotherapy. Escalation of adjunctive LTG therapy in patients taking VPA requires lower doses than in patients on enzyme inducing AEDs because rapid increase in...