Diclofenac-associated hepatotoxicity: analysis of 180 cases reported to the Food and Drug Administration as adverse reactions.

Diclofenac is a nonsteroidal anti-inflammatory drug approved in the United States in 1988 for the treatment of patients with osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis. To characterize the clinical, biochemical, and histological features and possible mechanisms of hepatic injury associated with its use, a retrospective analysis was undertaken of 180 patients whose cases were reported to the Food and Drug Administration from November 1988 through June 1991, as having had possible adverse reactions to diclofenac. Of the reported 180 cases, 79% were female, 71% were 60 years of age or older, and 77% had osteoarthritis. Sixty-seven percent of the cases were detected by symptoms and the remainder by abnormal laboratory tests. Seventy-five percent of the symptomatic patients (90 of 120) were jaundiced. Seven of the 90 icteric patients died. The biochemical pattern of injury was hepatocellular or mixed hepatocellular in 66% of cases. Only 8% had a pattern of cholestatic injury. The remainder, with modestly increased values of both transaminases and alkaline phosphatase, were considered "indeterminate," i.e., either mild hepatocellular or anicteric "cholestatic" injury. Sections of liver from 21 cases were available for study. Hepatic injury was apparent by 1 month after starting the drug in 24%, by 3 months in 63%, and by 6 months in 85% of cases. The latent period in 12% was 6 to 12 months, whereas in 3% it was greater than 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

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). CONCLUSION: 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.

Comparison of antibiotic therapy in presumptive bacterial conjunctivitis.

One hundred twenty patients who met criteria for presumptive bacterial infections of the conjunctiva were closely recorded for two weeks in a double-blind study that compared the effectiveness of gentamicin with a combination of neomycin and polymyxin B sulfates. The neomycin and polymyxin B combination demonstrated statistical superiority as measured by patient improvement and failure to respond to therapy. However, difficulties including chance distribution of bacteria and variability of organism resistance may have detracted from statistical results.