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

• Published in: European journal of clinical pharmacology 2014-03, Vol.70 (3), p.339-345
• Main Authors: Huber, Matthias, Andersohn, Frank, Bronder, Elisabeth, Klimpel, Andreas, Thomae, Michael, Konzen, Christine, Meyer, Oliver, Salama, Abdulgabar, Schrezenmeier, Hubert, Hildebrandt, Martin, Späth-Schwalbe, Ernst, Grüneisen, Andreas, Kreutz, Reinhold, Garbe, Edeltraut
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Agranulocytosis - chemically induced; Agranulocytosis - epidemiology; Berlin - epidemiology; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Case-Control Studies; Drug-Related Side Effects and Adverse Reactions - epidemiology; Female; Hematologic and hematopoietic diseases; Humans; Logistic Models; Male; Medical sciences; Middle Aged; Other diseases. Hematologic involvement in other diseases; Pharmaceuticals; Pharmacoepidemiology and Prescription; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Risk; Risk factors; Side effects; Young Adult
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-013-1618-1

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.