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Metamizole-induced agranulocytosis revisited: results from the prospective Berlin Case–Control Surveillance Study

  • Pharmacoepidemiology and Prescription
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Abstract

Purpose

Treatment with metamizole (dipyrone) has steadily increased in Germany over the last decade. The consequences of this increase for metamizole-induced agranulocytosis (MIA) are unclear. The present study addressed this topic using data from the Berlin Case–Control Surveillance Study.

Methods

Adult patients (≥18 years of age) with acute nonchemotherapy-induced agranulocytosis were identified by active surveillance in all 51 Berlin hospitals between 2000 and 2010. Cases related to metamizole were ascertained applying the drug causality criteria of the World Health Organization. The incidence rate of MIA was calculated and standardised by age and sex based on the German standard population in 2010.

Results

Twenty-six MIA cases out of 88 (30 %) patients with validated agranulocytosis were ascertained. The incidence of MIA was 0.96 (95 % confidence interval (CI) 0.95–0.97) cases per million per year. The median age of MIA cases was 50 years (quartile (Q)1 31 years; Q3 68 years) and 19 (73 %) of them were women. In 17 (65 %) cases, neutrophil granulocytes dropped below the value of 0.1 × 109 cells/L with three patients suffering from sepsis. Headache and postoperative pain were the most frequent indications for metamizole in outpatients (n = 16) and inpatients (n = 10), respectively. The median treatment duration was 6 days (Q1 4 days; Q3 19 days).

Conclusions

MIA persists as a severe condition in current pharmacotherapy. The continuous increase of metamizole applications should be critically assessed, especially in regard to indications in the outpatient setting and with respect to metamizole treatment duration.

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Acknowledgments

Cases were collected within the study ‘Berlin Case–Control Surveillance (FAKOS) of Serious Blood Dyscrasias’, which was funded by a grant from the Federal Institute for Drugs and Medical Devices (Bonn, Germany). We wish to thank all members of the Haematological Advisory Board (Hubert Schrezenmeier, Martin Hildebrandt, Ernst Späth-Schwalbe, Andreas Grüneisen, Abdulgabar Salama) and all hospitals contributing cases and controls to this study. A list of the hospitals is given in the Appendix. We wish to thank the Wissenschaftliches Institut der AOK (WIdO) Research Institute (Berlin, Germany) for the provided data on metamizole dispensation rates.

Contributions of Authors statement

Study concept and design: Edeltraut Garbe and Elisabeth Bronder; acquisition of data: Edeltraut Garbe, Elisabeth Bronder, Frank Andersohn, Michael Thomae, Christine Konzen and Giselle Sarganas; analysis and interpretation of data: Edeltraut Garbe, Matthias Huber, Andreas Klimpel, Frank Andersohn, Elisabeth Bronder, Michael Thomae, Reinhold Kreutz, Christine Konzen and Giselle Sarganas; drafting the manuscript: Matthias Huber and Edeltraut Garbe; critical revision of the manuscript: all authors; study supervision: Edeltraut Garbe and Elisabeth Bronder. All authors have approved the final draft submitted.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Institute of Clinical Pharmacology and Toxicology, Charité–Universitätsmedizin Berlin, Berlin, Germany

    Matthias Huber, Giselle Sarganas, Elisabeth Bronder, Andreas Klimpel, Christine Konzen & Reinhold Kreutz

  2. Institute for Social Medicine, Epidemiology and Health Economy, Charité–Universitätsmedizin Berlin, Berlin, Germany

    Frank Andersohn

  3. Department of Surgery, Maria-Heimsuchung Caritas Klinik Pankow, Berlin, Germany

    Michael Thomae

  4. Leibniz Institute for Prevention Research and Epidemiology–BIPS and University of Bremen, Achterstr. 30, 28359, Bremen, Germany

    Edeltraut Garbe

  5. Faculty for Human and Health Sciences, University of Bremen, Bremen, Germany

    Edeltraut Garbe

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  1. Matthias Huber
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  2. Frank Andersohn
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Correspondence to Edeltraut Garbe.

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Huber, M., Andersohn, F., Sarganas, G. et al. Metamizole-induced agranulocytosis revisited: results from the prospective Berlin Case–Control Surveillance Study. Eur J Clin Pharmacol 71, 219–227 (2015). https://doi.org/10.1007/s00228-014-1777-8

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  • DOI: https://doi.org/10.1007/s00228-014-1777-8

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