Redesigning Drug Approval – Redefining Drug Safety: The Felbamate – Bromfenac Paradigm

Presented at the American College of Clinical Pharmacology, September 1999, Washington, DC

In July of 1993, felbamate (Felbatol®) was approved for the treatment of Lennox-Gastaut (LG) syndrome in children, for which there was no effective treatment. Pre-market studies in ~1,000 patients failed to detect any serious ADRs. Within a year of marketing, reports of aplastic anemia and acute hepatic failure raised concerns regarding felbamate’s safety; however, the absence of any alternative pharmacologic treatment for LG influenced the FDA not to request the drug’s voluntary removal. On June 22, 1998, the NSAID bromfenac (Duract®) was voluntarily withdrawn from the market one year after introduction, due to reports of serious hepatic toxicity and 4 deaths. Hepatic toxicity reported in pre-market studies in ~2,600 patients caused the FDA to label bromfenac for administration for 10 or fewer days, naively hoping to minimize toxicity by limiting use. There was no alternative to felbamate, but there were many NSAIDs already on the market with more favorable safety profiles than bromfenac. Public policy issues regarding patient safety and physician exposure to an increased potential for legal liability (for prescribing a drug which has such an unfavorable benefit-to-risk ratio) require a more demanding safety requirement for approval. New drugs or “me-too” drugs with unfavorable pre-marketing safety records, or with a high potential for severe toxicity should no longer be approved.