Pemoline hepatotoxicity and postmarketing surveillance

Objective: To review the numerous reports of hepatotoxic adverse drug react ions (ADRs) ascribed to pemoline that were sent to the U.S. Food and Drug A dministration (FDA) between 1975 and 1996 and to describe the medical commu nity's lack of awareness of these reports. Method: All ADR reports from 197 5 through 1996 wherein pemoline was the suspect agent were obtained from th e FDA MedWatch Internet site, and some details of nine pemoline-related dea ths in youths were obtained directly from the FDA. The published literature on this subject was fully reviewed. Results: (1) In premarketing clinical trials with pemoline in the early 1970s, hepatic abnormalities were noted i n enzyme levels (1%-3% of youths receiving maintenance treatment). during r echallenges (6 of 6), and in biopsies (2 of 2).(2) Between 1975 and 1989, 1 2 cases of jaundice and 6 deaths in youths ascribed to pemoline hepatotoxic ity were reported to the FDA. (3) The first medical literature report of a serious ADR ascribed to pemoline was in a 1989 letter to the editor. (4) Ph ysicians generally only became aware of serious pemoline hepatotoxicity in December 1996. (5) Pemoline use increased until 1997, Conclusion: Limitatio ns in postmarketing surveillance and public reporting in the United States, particularly in the 1980s, largely accounted for delays in an appropriate response to pemoline hepatotoxicity.