Abstracts

With the current trend toward accelerated approval of drugs in the US, postmarketing reporting of adverse reactions has become an essential tool in establishing the safety profile of new drugs. Between 1993 to 2000, eight new antiepileptic drugs (AEDs) were approved by the Food and Drug Administration (FDA). While premarketing clinical trials suggested a relatively mild adverse effect profile for most of these new drugs, limited information was available at the time of their approval to accurately define their risks. To examine the significance of postmarketing adverse reaction reporting for the new AEDs, we reviewed safety labeling modifications made since their release., Safety labeling modifications made for the new AEDs from 1993 through December 2005 were identified using prescribing information and a search of the FDA MedWatch database., All the drugs underwent safety labeling changes during this period. In total, there were 38 safety labeling modifications with the median time to the first change being 2 years after introduction (range: 13 months to 12 years). The most common modification in safety labeling (n=14) involved the adverse reaction section of the prescribing information. Three of the 38 changes involved the addition of a black box warning (2 for felbamate and 1 for lamotrigine). All occurred within 3 years after the introduction to the market place. The remaining labeling modifications consisted of changes in the warnings (n=10), precautions (n=10), and clinical pharmacology (n=1) sections. Although the majority of labeling modifications came within the first 6 years after approval, mean cumulative function (MCF) analysis revealed no identifiable point at which additional changes were unlikely to be made., Over the past 13 years, a significant number of modifications have been made in the safety labeling of the new AEDs, ranging from black box warnings to the addition of new data in the adverse reactions tables. Recurrent data analysis failed to reveal a point at which additional safety information appeared unlikely, suggesting that the adverse effect profiles of the new AEDs may not yet be complete., (Supported by NIH.)