Factors influencing the incidence of lamotrigine-related skin rash

OBJECTIVE: To determine the incidences of serious add nonserious lamotrigin e-related rash, determine the risk factors for lamotrigine-related rash, an d evaluate the impact on the incidence of rash of the manufacturer's recomm endation to reduce the starting dose of lamotrigine. METHODS: This was a retrospective case record survey at five tertiary refer ral epilepsy centers in the UK. The risk factors for lamotrigine-related ra sh were identified by logistic regression. The independent factors tested w ere gender, age, epilepsy type, concurrent medication, and starting dose of lamotrigine. The incidences of rash before and after the recommendation of reduction in starting dose were compared by chi(2) analysis. RESULTS: A total Of 1050 patients were included. The incidences of serious and nonserious rash were 1.1% (95% CI 0.5% to 1.8%) and 7% (95% CI 5.5% to 8.6%), respectively. Females were at higher risk of developing rash than we re males, with a relative risk of 1.8 (95% CI 1.2 to 2.8). The starting dos e of lamotrigine was reduced in response to the manufacturer's recommendati on, and there was a significant reduction (p = 0.045) in the incidence of s erious rash, from 1.5% (12/805) to 0% (0/245). However, there was no reduct ion in the overall incidence of lamotrigine-related rash, with 63/805 (8%) before and 23/245 (9%) after the recommendation. CONCLUSIONS: Failure to detect a reduction in the incidence of lamotrigine- related rash since the new (reduced) recommended starting dose of lamotrigi ne may arise from failure to reduce the starting dose below a critical thre shold level, incomplete compliance with current recommendations, or insuffi cient sample size. The results of this and other studies show that the star ting dose of lamotrigine is a significant factor affecting the incidence of rash; furthermore, this study also shows that significant reduction in the incidence of serious rash can be achieved by reducing the starting dose. T herefore, clinicians should not deviate from the recommendations.