Sulindac-associated hepatic injury: analysis of 91 cases reported to the Food and Drug Administration.
BACKGROUND
Recent emphasis on nonsteroidal anti-inflammatory drug (NSAID)-associated hepatic injury blurs differences between NSAIDs. Accordingly, examination of hepatic injury by individual NSAIDs seemed warranted. Sulindac-associated hepatic injury was selected.


METHODS
From 338 reports submitted to the Food and Drug Administration, 247 were considered inadequate or unconvincing for sulindac toxicity. The remaining 91 cases of reactions to the drug were analyzed. In 15 there was histological material available.


RESULTS
There were four deaths, three attributed to severe hypersensitivity and one to fulminant hepatic failure. Two thirds of the cases had clinical hallmarks of hypersensitivity. The ratio of females to males was 3.5:1; 69% of the patients were over 50 years of age. Jaundice was recorded in 67% of the patients. The pattern was cholestatic in 43%, hepatocellular in 25%, mixed in 12%, and indeterminate in 20% of the patients. Eosinophilia was significantly more frequent in patients with cholestatic injury (40%) than in those with hepatocellular injury (0).


CONCLUSIONS
Sulindac injury involves females more than males. It can lead to cholestatic or hepatocellular injury, most often because of immunological idiosyncrasy. In some patients, metabolic idiosyncrasy may be the mechanism. This study illustrates the utility of analysis of adverse reaction reports in characterizing drug-induced injury.
Tarazi
E M
EM
Food and Drug Administration, Center for Drug Evaluation and Research, Rockville, Maryland.
Harter
J G
JG
Zimmerman
H J
HJ
Ishak
K G
KG
Eaton
R A
RA
D000328:Adult; D000368:Aged; D056486:Chemical and Drug Induced Liver Injury; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013467:Sulindac / Q000009:adverse effects*; D014481:United States; D014486:United States Food and Drug Administration
D013467:Sulindac