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

Karin Hedenmalm (), Alexandra Pacurariu, Jim Slattery, Xavier Kurz, Gianmario Candore and Rob Flynn
Additional contact information
Karin Hedenmalm: European Medicines Agency
Alexandra Pacurariu: European Medicines Agency
Jim Slattery: European Medicines Agency
Xavier Kurz: European Medicines Agency
Gianmario Candore: European Medicines Agency
Rob Flynn: European Medicines Agency

Drug Safety, 2021, vol. 44, issue 9, No 6, 973-985

Abstract: Abstract Introduction The analgesic metamizole, which has been withdrawn from the market in several countries due to the risk of agranulocytosis but is still available on the market in Germany and some other countries, has been associated with liver injury in published case reports; however, epidemiological studies on the risk of liver injury are limited. Objective The aim of this study was to compare the risk of liver injury up to 270 days after the first start of treatment with metamizole with the corresponding risk in patients starting treatment with paracetamol, using a retrospective cohort incident user design. Methods The first prescription for either metamizole or paracetamol in the Intercontinental Medical Statistics (IMS)® Disease Analyzer Germany database during the study period (2009–2018) was identified in patients with at least 365 days of observation and no prior diagnosis of liver events, cancer or HIV, or treatment within the last 6 months with hepatotoxic drugs typically administered for chronic conditions. Each patient was followed for specific liver events for 90 days after the prescription. In case of a new prescription within 90 days, a new 90-day observation period started, up to a maximum of 270 days. Cox regression was used to compare the risk of liver injury in the two groups. Results Metamizole was associated with a higher risk of liver injury compared with paracetamol (adjusted hazard ratio 1.69, 95% confidence interval 1.46–1.97). Sensitivity analyses were performed to evaluate the robustness of these findings. In all the sensitivity analyses, metamizole was still associated with a higher risk of liver injury, including an analysis where naproxen was used as a comparator instead of paracetamol. Conclusions Results from this study support previous studies suggesting that metamizole is associated with a significant risk of liver injury. Nevertheless, a possible impact of residual confounding cannot be excluded.

Date: 2021
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
http://link.springer.com/10.1007/s40264-021-01087-7 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:spr:drugsa:v:44:y:2021:i:9:d:10.1007_s40264-021-01087-7

Ordering information: This journal article can be ordered from
http://www.springer.com/adis/journal/40264

DOI: 10.1007/s40264-021-01087-7

Access Statistics for this article

Drug Safety is currently edited by Nitin Joshi

More articles in Drug Safety from Springer
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().