Metamizole and risk of hepatotoxicity –comparative cohort study of incidence of hepatic events in patients treated with metamizole vs. patients treated with paracetamol in IMS Disease Analyzer Germany between January 2009 and December 2018 (Metamizole and hepatotoxicity)

Study type

• Study topic:
  Human medicinal product

  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Comparative study

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  METAMIZOLE
• Medical condition to be studied:
  Drug-induced liver injury

Population studied

• Short description of the study population:
  The study focused on incident users of metamizole and paracetamol from 1 January 2009 to 31 December 2018.; Patients with less than 365 days of observation and those with a history of cancer, HIV, viral hepatitis, liver disease, or Budd-Chiari syndrome was excluded from the study.
• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Hepatic impaired
• Estimated number of subjects:
  600000

Study design details

• Main study objective:
  This study aims to quantify the incidence of hepatic events in patients treated with metamizole compared to patients treated with paracetamol.
• Outcomes:
  Drug-induced liver injury, classified as a composite outcome of various hepatic terms (see protocol). in case of sufficient data, we will analyse separately toxic liver disease (ICD 10 code K71), hepatic failure not elsewhere classified (ICD 10 code K72) and other hepatic events (ICD 10 codes K75-K76).
• Data analysis plan:
  A comparative cohort will be created, where the relative risk will be calculated with the Cox Proportional Hazards models. all variables will be recorded at baseline and not integrated as time-dependent. The analysis will be adjusted for age (continuous), gender and the identified confounders that will show an effect on the risk estimate (significant association in univariate models and more than 10% change in risk estimate). Missing data will be dealt with through list-wise deletion (complete case analysis).

Documents

Study publications

Hedenmalm K, Pacurariu A, Slattery J, Kurz X, Candore G, Flynn R. Is there an i…