Abstracts

Rationale: Association of valproate (VPA) and lamotrigine (LTG) has been documented as effective for treatment of refractory epilepsy. However, adverse-effects, especially skin rash, remain a major concern. In order to minimize these effects, we developed a prospective protocol with lower doses of introduction and titration. Methods: In the first two weeks, 0.1-0.15 mg/ kg of LTG was introduced in one daily dose added to VPA. In weeks 3 and 4, 0.1 mg/Kg/day of LTG was added in one or two divided doses. Patients returned every 15 days for dose adjustment of 0.2 mg/Kg/day. Introduction consisted of a 10-12 week dose escalation period. After this, doses of VPA were reduced in 50%. The mean dose of LTG in the maintenance period was 1.2mg/kg/day [minimum (0.4mg/kg/day) and maximum (3mg/kg/day)].Results: VPA-LTG co-administration was considered effective (> 50% seizure frequency decrease) in 39 children (81.3%), of which 6 (7.9%) were seizure-free. Tremor occurred in six patients (11.8%); urinary incontinence in one (2.0%). Drowsiness, nausea and vomiting were not reported. Skin rash occurred in 5.9% (3/51) patients, of which two with well-documented history of AEDs hypersensitivity.Conclusions: In our series, risks were lessened with slow introduction, providing safer conditions for the use of this association in a population in need of therapeutic options.