title: Drug-induced agranulocytosis in the Berlin case-control surveillance study.
abstract: OBJECTIVE
  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.
authors.affiliation: Institute of Clinical Pharmacology and Toxicology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Huber
authors.forename: Frank
authors.initials: F
authors.lastname: Andersohn
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bronder
authors.forename: Andreas
authors.initials: A
authors.lastname: Klimpel
authors.forename: Michael
authors.initials: M
authors.lastname: Thomae
authors.forename: Christine
authors.initials: C
authors.lastname: Konzen
authors.forename: Oliver
authors.initials: O
authors.lastname: Meyer
authors.forename: Abdulgabar
authors.initials: A
authors.lastname: Salama
authors.forename: Hubert
authors.initials: H
authors.lastname: Schrezenmeier
authors.forename: Martin
authors.initials: M
authors.lastname: Hildebrandt
authors.forename: Ernst
authors.initials: E
authors.lastname: Späth-Schwalbe
authors.forename: Andreas
authors.initials: A
authors.lastname: Grüneisen
authors.forename: Reinhold
authors.initials: R
authors.lastname: Kreutz
authors.forename: Edeltraut
authors.initials: E
authors.lastname: Garbe
mesh_terms: D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D000380:Agranulocytosis / Q000139:chemically induced* / Q000453:epidemiology; D001604:Berlin / Q000453:epidemiology; D016022:Case-Control Studies; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012306:Risk; D055815:Young Adult