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.
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The authors declare that they have no conflict of interest.
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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