Safety review of adult clinical trial experience with lamotrigine.

To date approximately 4000 adults > 12 years of age have been treated with lamotrigine in Glaxo Wellcome sponsored clinical trials. Review of the data from these trials shows lamotrigine to be effective and well tolerated in both add-on and monotherapy treatment. Safety of lamotrigine was comparable to that of other anticonvulsants in add-on controlled clinical trials. In addition, fewer than half the number of patients in monotherapy studies who were taking lamotrigine discontinued treatment because of adverse events compared to those taking carbamazepine and phenytoin. Most of the reported adverse events seen in lamotrigine treated patients in all studies were judged by the investigator to be mild or moderate in severity; few of the adverse events resulted in the withdrawal of patients from studies. Analysis of vital signs and clinical laboratory data have revealed no undesirable effect of lamotrigine on major systems of the body. The most concerning adverse event has been rash. In clinical trials, this has most often been limited to a simple morbilliform rash which is not associated with evidence of systemic involvement. The incidence of Stevens-Johnson syndrome (SJS) in clinical trials is approximately 1 in 1000. Rash associated with lamotrigine has typically occurred within the first 8 weeks of treatment. Data from clinical trials clearly point to exceeding currently recommended dosage guidelines of lamotrigine and co-administration of valproic acid (valproate sodium) as risk factors for rash. Early in 1997, Glaxo Wellcome strengthened existing warnings in the product label regarding the risk of rash and reinforced the importance of adherence to administration guidelines in an effort to reduce the incidence of rash.