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Updated: Oct 28, 2025

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
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Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

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Is There an Increased Risk of Hepatotoxicity with Metamizole? A Comparative Cohort Study in Incident Users

Karin Hedenmalm1,2, Alexandra Pacurariu3, Jim Slattery4

  • 1Data Analytics and Methods Task force, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS, Amsterdam, The Netherlands. karin.hedenmalm@ema.europa.eu.

Drug Safety
|July 17, 2021
PubMed
Abstract

Insights

Metamizole use significantly increases the risk of liver injury compared to paracetamol. This study confirms previous findings on metamizole

Area of Science:

  • Pharmacovigilance
  • Hepatology
  • Epidemiology

Background:

  • Metamizole, an analgesic available in Germany, has been linked to liver injury in case reports.
  • Epidemiological data on metamizole-associated liver injury risk are limited.
  • This study addresses the need for robust epidemiological evidence on metamizole's liver safety.

Purpose of the Study:

  • To compare the risk of liver injury associated with metamizole versus paracetamol.
  • To evaluate liver injury risk up to 270 days post-initiation of metamizole or paracetamol treatment.
  • To provide evidence on metamizole's hepatotoxicity in a real-world setting.

Main Methods:

  • Retrospective cohort incident user design using the IMS Disease Analyzer Germany database (2009-2018).
  • Inclusion criteria: patients with no prior liver events, cancer, or HIV, and no recent use of hepatotoxic drugs.
  • Follow-up for liver events up to 270 days, with Cox regression analysis for risk comparison.

Main Results:

  • Metamizole was associated with a significantly higher risk of liver injury compared to paracetamol (aHR 1.69, 95% CI 1.46-1.97).
  • Sensitivity analyses, including using naproxen as a comparator, consistently supported the higher risk with metamizole.
  • Findings remained robust across various analytical approaches.

Conclusions:

  • This study supports previous evidence indicating a significant risk of liver injury with metamizole.
  • The findings highlight the importance of monitoring for hepatotoxicity in patients using metamizole.
  • While results are compelling, potential residual confounding cannot be entirely ruled out.

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