title: Population-based drug-induced agranulocytosis.
abstract: BACKGROUND
  Since the publication of a major international case-control study on the risk of agranulocytosis associated with the use of medicines in the 1980s, many new drugs have been introduced in therapeutics.
  
  
  METHODS
  Seventeen units of hematology contribute to the case-control surveillance of agranulocytosis and aplastic anemia in Barcelona, Spain. After a follow-up of 78.73 million person-years, 177 community cases of agranulocytosis were compared with 586 sex-, age, and hospital-matched control subjects with regard to previous use of medicines.
  
  
  RESULTS
  The annual incidence of community-acquired agranulocytosis was 3.46:1 million, and it increased with age. The fatality rate was 7.0%, and the mortality rate was 0.24:1 million. The drug most strongly associated with a risk of agranulocytosis was ticlopidine hydrochloride with an odds ratio (OR) of 103.23 (95% confidence interval [CI], 12.73-837.44), followed by calcium dobesilate (OR, 77.84 [95% CI, 4.50-1346.20]), antithyroid drugs (OR, 52.75 [95% CI, 5.82-478.03]), dipyrone (metamizole sodium and metamizole magnesium) (OR, 25.76 [95% CI, 8.39-179.12]), and spironolactone (OR, 19.97 [95% CI, 2.27-175.89]). Other drugs associated with a significant risk were pyrithyldione, cinepazide, aprindine hydrochloride, carbamazepine, sulfonamides, phenytoin and phenytoin sodium, beta-lactam antibiotics, erythromycin stearate and erythromycin ethylsuccinate, and diclofenac sodium. Individual attributable incidences for all these drugs, which collectively accounted for 68.6% of cases, were less than 1:1 million per year.
  
  
  CONCLUSIONS
  Agranulocytosis is rare but serious. A few drugs account for two thirds of the cases. Our results also provide reassurance regarding the risk associated with a number of newly marketed drugs.
authors.affiliation: Fundació Institut Català de Farmacologia, Universitat Autònoma de Barcelona, Clinical Pharmacology Service, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Luisa
authors.initials: L
authors.lastname: Ibáñez
authors.forename: Xavier
authors.initials: X
authors.lastname: Vidal
authors.forename: Elena
authors.initials: E
authors.lastname: Ballarín
authors.forename: Joan-Ramon
authors.initials: JR
authors.lastname: Laporte
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology; D000700:Analgesics / Q000009:adverse effects*; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance; D012189:Retrospective Studies; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D015996:Survival Rate
chemical_list: D000700:Analgesics; D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal