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Drug-induced agranulocytosis in the Berlin case–control surveillance study

  • Pharmacoepidemiology and Prescription
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Abstract

Purpose

Drug-induced agranulocytosis (DIAG) is a rare but serious adverse drug reaction. The Berlin Case–Control Surveillance Study (FAKOS) aimed to identify pharmaceuticals with an increased risk for this condition.

Methods

Adult patients with acute non-chemotherapy–induced agranulocytosis, developed in hospital or in the outpatient setting, were ascertained by active surveillance in all 51 Berlin hospitals between the years 2000 and 2010. Applying the criteria of the World Health Organization, a standardized drug causality assessment was conducted for each agranulocytosis patient to determine possible drug aetiology. Drug risks were quantified in a case–control design with unconditional logistic regression analysis.

Results

Sixty-three out of 88 validated cases of agranulocytosis were identified as being at least probably drug-related. Drug causality assessment resulted in 36 pharmaceuticals with a certain or probable relationship to agranulocytosis. Drugs involved in ≥ 3 cases with a probable or certain causality were metamizole (dipyrone) (N = 10), clozapine (N = 6), sulfasalazine (N = 5), thiamazole (N = 5), and carbamazepine (N = 3). In case–control analysis, six drugs were identified with significant odds ratios for DIAG. The highest odds ratios were observed for clozapine, sulfasalazine, and thiamazole.

Conclusions

Our findings are generally in agreement with those of earlier case–control studies. The spectrum of drugs causing acute agranulocytosis has not changed considerably over recent years, despite many newly marketed drugs. Evidence for induction of agranulocytosis by some new pharmaceuticals is supported.

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Acknowledgments

Cases were collected within the study “Berlin Case–Control Surveillance (FAKOS) of Serious Blood Dyscrasias”, which is supported by a grant from the Federal Institute for Drugs and Medical Devices (Bonn, Germany). We wish to thank all hospitals contributing cases and controls to this study. A list of the hospitals is provided in a separate appendix.

Contributions of Authors statement

Study concept and design: Edeltraut Garbe, Elisabeth Bronder; acquisition of data: Edeltraut Garbe, Elisabeth Bronder, Frank Andersohn, Michael Thomae, Christine Konzen; analysis and interpretation of data: Edeltraut Garbe, Reinhold Kreutz, Andreas Klimpel, Matthias Huber, Frank Andersohn, Elisabeth Bronder, Michael Thomae, Christine Konzen; laboratory work: Abdulgabar Salama, Oliver Meyer; Haematology advisory board: Hubert Schrezenmeier, Martin Hildebrandt, Ernst Späth-Schwalbe, Andreas Grüneisen, Abdulgabar Salama; drafting the manuscript: Matthias Huber; critical revision of the manuscript: all authors; study supervision: Edeltraut Garbe, 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, 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. Institute for Transfusion Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany

    Oliver Meyer & Abdulgabar Salama

  5. DRK Blood Transfusion Service Baden-Württemberg–Hessen, Institute of Clinical Transfusion Medicine and Immunogenetics Ulm and University Hospital Ulm, Ulm, Germany

    Hubert Schrezenmeier

  6. Interdisciplinary Centre of Cell Therapy, Technical University of Munich, Munich, Germany

    Martin Hildebrandt

  7. Medical Department, Hematology, Oncology and Gastroenterology, Vivantes Klinkum Spandau, Berlin, Germany

    Ernst Späth-Schwalbe

  8. Department of Internal Medicine—Haematology and Oncology, Vivantes Klinikum Neukölln, Berlin, Germany

    Andreas Grüneisen

  9. Leibniz - Institute for Prevention Research and Epidemiology - BIPS, Achterstr. 30, 28359, Bremen, Germany

    Edeltraut Garbe

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

    Edeltraut Garbe

Authors
  1. Matthias Huber
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  2. Frank Andersohn
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  3. Elisabeth Bronder
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  4. Andreas Klimpel
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  5. Michael Thomae
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  6. Christine Konzen
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  7. Oliver Meyer
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  8. Abdulgabar Salama
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  9. Hubert Schrezenmeier
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  10. Martin Hildebrandt
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  11. Ernst Späth-Schwalbe
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  12. Andreas Grüneisen
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  13. Reinhold Kreutz
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  14. Edeltraut Garbe
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Corresponding author

Correspondence to Edeltraut Garbe.

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Huber, M., Andersohn, F., Bronder, E. et al. Drug-induced agranulocytosis in the Berlin case–control surveillance study. Eur J Clin Pharmacol 70, 339–345 (2014). https://doi.org/10.1007/s00228-013-1618-1

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  • DOI: https://doi.org/10.1007/s00228-013-1618-1

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