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: Luisa Ibáñez, Xavier Vidal, Elena Ballarín, Joan-Ramon Laporte
• Journal: Archives of internal medicine (Arch Intern Med) Vol. 165 Issue 8 Pg. 869-74 (Apr 25 2005) ISSN: 0003-9926 [Print] United States
• PMID: 15851637 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Anti-Bacterial Agents
• Anti-Inflammatory Agents, Non-Steroidal

Topics

• Adolescent
• Adult
• Aged
• Agranulocytosis (blood, chemically induced, epidemiology)
• Analgesics (adverse effects)
• Anti-Bacterial Agents (adverse effects)
• Anti-Inflammatory Agents, Non-Steroidal (adverse effects)
• Female
• Follow-Up Studies
• Humans
• Incidence
• Leukocyte Count
• Male
• Middle Aged
• Population Surveillance
• Retrospective Studies
• Risk Factors
• Spain (epidemiology)
• Survival Rate