Serious liver injury induced by Nimesulide: an international collaborative study

Arch Toxicol. 2021 Apr;95(4):1475-1487. doi: 10.1007/s00204-021-03000-8. Epub 2021 Mar 24.

Abstract

Nimesulide is a non-steroidal anti-inflammatory drug still marketed in many countries. We aim to analyze the clinical phenotype, outcome, and histological features of nimesulide-induced liver injury (nimesulide-DILI). We analyzed 57 cases recruited from the Spanish and Latin American DILI registries. Causality was assessed by the RUCAM scale. Mean age of the whole case series was 59 years (86% women) with a median time to onset of 40 days. A total of 46 patients (81%) were jaundiced. Nimesulide-DILI pattern was hepatocellular in 38 (67%), mixed in 12 (21%), and cholestatic in 7 (12%) cases. Transaminases were elevated with a mean of nearly 20-fold the upper limit of normality (ULN), while alkaline phosphatase showed a twofold mean elevation above ULN. Total bilirubin showed a mean elevation of 13-fold the ULN. Liver histology was obtained in 14 cases (25%), most of them with a hepatocellular pattern. Median time to recovery was 60 days. Overall, 12 patients (21%) developed acute liver failure (ALF), five (8.8%) died, three underwent liver transplantation (5.3%), and the remaining four resolved. Latency was ≤ 15 days in 12 patients (21%) and one patient developed ALF within 7 days from treatment initiation. Increased total bilirubin and aspartate transaminase levels were independently associated with the development of ALF. In summary, nimesulide-DILI affects mainly women and presents typically with a hepatocellular pattern. It is associated with ALF and death in a high proportion of patients. Shorter (≤ 15 days) duration of therapy does not prevent serious nimesulide hepatotoxicity, making its risk/benefit ratio clearly unfavorable.

Keywords: Acute liver failure; Cholestasis; Hepatitis; Hepatotoxicity; NSAID; Nimesulide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Bilirubin / metabolism
  • Chemical and Drug Induced Liver Injury / epidemiology
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemical and Drug Induced Liver Injury / physiopathology
  • Child
  • Cholestasis / chemically induced
  • Cholestasis / epidemiology
  • Cohort Studies
  • Female
  • Humans
  • Jaundice / chemically induced
  • Jaundice / epidemiology
  • Latin America / epidemiology
  • Liver Failure, Acute / chemically induced*
  • Liver Failure, Acute / epidemiology
  • Male
  • Middle Aged
  • Registries
  • Risk Factors
  • Spain / epidemiology
  • Sulfonamides / administration & dosage
  • Sulfonamides / adverse effects*
  • Time Factors
  • Young Adult

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Sulfonamides
  • Bilirubin
  • nimesulide