Abstracts

RATIONALE: Patients may differ in their sensitivity to side effects of antiepileptic drugs (AEDs) based on their age. Children and elderly patients can be particularly vulnerable. Reported here are the findings regarding the age-related tolerability and safety of TPM monotherapy.
METHODS: Two clinical trials have been conducted with TPM as monotherapy in patients with no or limited exposure to AEDs. The TPM doses used in these studies were 50 (25 if weight [lt]50 kg), 100, 200, and 500 mg/day. Treatment-emergent adverse events (AEs) were coded with the same modified WHOART dictionary, allowing databases to be integrated and analyzed for three age groups: children ([lt]16 yrs), adult (17-64 yrs), and elderly ([gt]65 yrs).
RESULTS: The safety dataset was composed of 661 patients (children, N=114; adults, N=479; elderly, N=68) treated with TPM for up to 2.2 yrs, with most patients treated 6 mos or more. The most common AEs (incidence [gt]10%) reported during TPM treatment were paresthesia (27%), headache (21%), fatigue (20%), upper respiratory tract infection (16%), somnolence (13%), nausea (11%), anorexia (11%) and weight decrease (11%). Incidences of these AEs were generally similar across age groups with the exception of a higher incidence in the elderly of ataxia (12% vs. 3% and 0% in adults and children, respectively) and confusion (10% vs. 5% and 1%). Incidences of other cognitive complaints were similar or somewhat lower in elderly: cognitive problems NOS, 0% in elderly subjects vs. 3% and 2% in adults and children, respectively; concentration/attention difficulty, 6% in elderly vs. 8% in adults and children; and memory difficulty, 1% vs. 9% and 5%. AEs occurring with lower incidence in children were paresthesia (8% in children vs. 32% and 22% in adults and elderly, respectively), dizziness (4% vs. 16% and 18%), nausea (6% in children vs. 12% in adults and elderly), and weight decrease (5% vs. 12% in adults and elderly). In a comparative monotherapy study, TPM 100 mg/day proved to be an appropriate initial target dose for newly diagnosed epilepsy, being at least as effective as carbamazepine and valproate. With this dose, the proportion of patients discontinuing TPM due to AEs was 11% in children; adults, 21%; and elderly, 20%.
CONCLUSIONS: The occurrence of certain AEs may display age-related patterns, but children and elderly patients do not appear to be more vulnerable to side effects during TPM monotherapy than adults. Although TPM is well-tolerated across age groups, children may be less likely to discontinue TPM due to side effects than adults and elderly.
Support: The R.W. Johnson Pharmaceutical Research Institute.
Disclosure: Salary - Wang, Neto- R.W.Johnson Pharmaceutical Research Institute; Grant - Clinical Investigator- Mattson- Ortho-McNeil and R.W.Johnson Pharmaceutical Research Institute; Stock - Wang, Neto- R.W.Johnson Pharmaceutical Research Institute; Honoraria - Mattson- Ortho-McNeil