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Hematological safety of metamizole: retrospective analysis of WHO and Swiss spontaneous safety reports

  • Pharmacoepidemiology and Prescription
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Abstract

Purpose

Since the 1970s, the use of metamizole is controversial due to the risk of agranulocytosis. The aim of this study was to analyze individual case safety reports (ICSRs) of metamizole-associated hematological adverse drug reactions (ADRs).

Methods

International and Swiss metamizole-associated ICSR concerning selected hematological ADR were retrieved from VigiBase™, the World Health Organization Global Database of ICSR, and the Swiss Pharmacovigilance Database. We evaluated demographic data, co-medication, drug administration information, dose and duration of metamizole treatment, as well as the latency time of ADR, their course, and severity. The subgroup analysis of Swiss reports allowed us to analyze cases with fatal outcome more in depth and to estimate a rough minimal incidence rate.

Results

A total of 1417 international and 77 Swiss reports were analyzed. Around 52 % of the international and 33 % of the Swiss metamizole-associated hematological ADR occurred within a latency time of ≤7 days. More women were affected. The annual number of hematological reports and those with fatal outcome increased over the last years parallel to metamizole sales figures. In Switzerland, the minimal incidence rate of agranulocytosis was 0.46–1.63 cases per million person-days of use (2006–2012). Female sex, old age, pancytopenia, and co-medication with methotrexate were striking characteristics of the seven Swiss fatal cases.

Conclusions

Metamizole-associated hematological ADR remain frequently reported. This is underscored by increasing annual reporting rates, which mainly reflect growing metamizole use. Early detection of myelotoxicity and avoidance of other myelotoxic substances such as methotrexate are important measures for preventing fatalities.

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Acknowledgments

The authors would like to thank Sara Hult, member of the analysis team of the Uppsala Monitoring Centre, the WHO Collaborating Centre for International Drug Monitoring, for providing the data and for answering our questions. We also would like to thank Guy Levy from the Vigilance Unit of Swissmedic for his collaboration. We thank also Sanofi-Aventis SA, Streuli Pharma AG, and Sintetica SA for providing the sales figures of their metamizole preparations in Switzerland. We thank also the Senglet-Foundation, the foundation for the promotion of young pharmaceutical researchers in Basel, for their financial support.

Author contribution

Performed research: LB, AT, PE, ARB. Analyzed data: LB, AT, MH, SK, ARB. Wrote manuscript: LB, SK, ARB. All authors contributed to the review and final approval of the manuscript.

Conflict of interest

The authors declare that there are no conflicts of interest regarding this work.

Author information

Authors and Affiliations

  1. Division of Clinical Pharmacology and Toxicology, University Hospital, Hebelstrasse 2, 4031, Basel, Switzerland

    Lea S. Blaser, Alexandra Tramonti, Manuel Haschke, Stephan Krähenbühl & Alexandra E. Rätz Bravo

  2. Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland

    Pascal Egger

  3. Regional Pharmacovigilance Center, University Hospital, Basel, Switzerland

    Alexandra E. Rätz Bravo

Authors
  1. Lea S. Blaser
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  2. Alexandra Tramonti
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  3. Pascal Egger
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  4. Manuel Haschke
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  5. Stephan Krähenbühl
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  6. Alexandra E. Rätz Bravo
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Corresponding author

Correspondence to Stephan Krähenbühl.

Additional information

Accompanying statement

The data for this work were obtained from the WHO Collaborating Centre for International Drug Monitoring, Uppsala, Sweden and from the Swiss health authority, Swissmedic, in Berne, Switzerland. Data from spontaneous reporting are inhomogeneous as a result of different reporting policies worldwide and are vulnerable to underreporting and reporting bias. The information contained in this work is therefore not homogeneous, at least with respect to origin and also to likelihood that the pharmaceutical product caused the adverse reaction. The conclusions drawn based on these data do not necessarily represent the opinion of the World Health Organization or of Swissmedic.

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Blaser, L.S., Tramonti, A., Egger, P. et al. Hematological safety of metamizole: retrospective analysis of WHO and Swiss spontaneous safety reports. Eur J Clin Pharmacol 71, 209–217 (2015). https://doi.org/10.1007/s00228-014-1781-z

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  • DOI: https://doi.org/10.1007/s00228-014-1781-z

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