Predictors of lamotrigine-associated rash

Purpose: To determine the predictors of lamotrigine-associated rash (LTG-rash) and the incidence of serious and benign LTG-rash to individualize risk assessment in a given patient. Methods: We reviewed the charts of all 988 outpatients seen at the Columbia Comprehensive Epilepsy Center between January 1, 2000, and December 31, 2003, who received LTG. Charts were reviewed for documentation of rash developing from any medication, including antiepileptic drugs (AEDs) and non-AEDs, and including remote histories of drug-related rashes. Demographics, medical history, and medication variables were tested as potential predictors of LTG-rash. Results: Fifty-six (5.7%) of 988 patients experienced rash attributed to LTG, and 39 (3.9%) discontinued LTG because of rash. No patients experienced toxic epidermal necrolysis or required hospitalization because of LTG-rash. One case of mild probable Stevens-Johnson syndrome occurred. In multivariate analysis, a history of rash after another AED was the strongest predictor of LTG-rash (13.9% vs. 4.6%; OR = 3.62; p < 0.001), with children younger than 13 years also experiencing significantly more LTG-rash (10.7% vs. 4.3%; OR = 2.77; p < 0.001). In children with a rash attributed to another AED, 18.2% experienced LTG-rash, whereas in adults without a rash from another AED, 3% experienced LTG-rash. Conclusions: Based on this retrospective analysis, a history of another AED-related rash is the greatest risk factor for developing rash to LTG; age younger than 13 years is also a risk factor. Severe rash is rare when using the currently recommended titration rate.