Abstract

Nimesulide is a selective inhibitor of the enzyme cyclooxygenase 2. Although considered to be a safe drug, cases of acute hepatitis and fulminant liver failure have been reported in Europe, the United States and South America, especially among elderly female patients. Until now, there had not been any reports in the literature relating to Brazilian subjects. An 81-year old female who had been using nimesulide therapy for six days presented hematemesis and epistaxis two days before hospitalization. Clinical examination showed an extensive coagulation disorder, diffuse hematomas, hypotension and tachypnea. Laboratory tests revealed abnormalities in coagulation tests; leukocytosis; reduced platelet, hemoglobin and red blood cell counts; and elevated direct bilirubin, serum aspartate transaminase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase and renal function biomarkers. Hepatitis B and C tests were not reactive. Carcinoembryonic antigen (CEA), CA-19-9 and CA-125 levels were increased by, respectively, 1,000, 10,000 and 13 fold, whereas the alpha-fetoprotein level was normal, thus indicating a malignant tumor in the bile duct that did not originate from the liver. Thirty-six hours after hospitalization, the patient's condition worsened, leading to death. The necropsy findings included acute hepatitis with hepatocellular collapse, as well as metastasis of a carcinoma, probably from the bile duct. Despite the carcinoma presented by the patient, nimesulide use may have contributed towards the fatal acute liver failure. Until this issue has been clarified, caution is required in prescribing nimesulide for liver disease patients.

Highlights

  • Nimesulide (NIM) has analgesic, anti-inflammatory and antipyretic activity due to its potent inhibitory effects on the enzyme cyclooxygenase 2 (COX-2), while causing relatively low occurrence of gastrointestinal injury.[1]

  • The hepatic events that have been reported during treatment with nimesulide include asymptomatic and reversible elevation of liver enzymes,[8,9] acute hepatitis associated with hepatocellular necrosis, cholestasis and some isolated cases of fatal acute liver failure.[10,11]

  • We report on the case of an elderly female with hepatic adenocarcinoma metastasis from the biliary duct, with early onset of hematological disorders after ingestion of nimesulide at therapeutic doses

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Summary

Introduction

Nimesulide (NIM) has analgesic, anti-inflammatory and antipyretic activity due to its potent inhibitory effects on the enzyme cyclooxygenase 2 (COX-2), while causing relatively low occurrence of gastrointestinal injury.[1]. The renal and hepatic damage advanced, as demonstrated by higher levels of urea, creatinine, AST, ALT and bilirubins (including the indirect form).

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