Pemoline-associated fulminant liver failure: Testing the evidence for causation

Background: Pemoline is a central nervous system stimulant used in treating children with attention deficit-hyperactivity disorder. Hepatotoxicity has been commonly reported in association with pemoline; however, only two reports of cases of fatal liver failure have been published. Objectives: We report on a 14-year-old boy who received concomitant pemoline and methylphenidate in whom fulminant liver failure occurred and for whom liver transplantation failed. Other causes of fulminant liver failure were ruled out, and the liver biopsy was suggestive of drug toxicity. We estimated the probability that these three cases represent an increased risk of fulminant liver failure associated with pemoline. Results: Based on the three known cases of fatal liver failure associated with pemoline use, we calculated that a child receiving pemoline has a relative risk of development of fulminant liver failure of 45.3 (95% confidence interval, 4.1 to 510). This highly significant association (p < 0.001) suggests causation. Conclusions: Because pemoline has been widely used in recent years, further studies are needed to better quantify this risk in children with attention deficit-hyperactivity disorder.