FDA arthritis advisory committee meeting: risks of agranulocytosis/aplastic anemia, flank pain, and adverse gastrointestinal effects with the use of nonsteroidal antiinflammatory drugs
✍ Scribed by Harold E. Paulus
- Publisher
- John Wiley and Sons
- Year
- 1987
- Tongue
- English
- Weight
- 290 KB
- Volume
- 30
- Category
- Article
- ISSN
- 0004-3591
No coin nor oath required. For personal study only.
✦ Synopsis
Agranulocytosislaplastic anemia with the use of nonsteroidal antiinflammatory drugs. A discussion of this subject was prompted by the recently published report of the International Agranulocytosis and Aplastic Anemia (IAAA) Study Group on the risks of those events in relation to use of analgesics (1). Scattered reports that associate agranulocytosis and aplastic anemia with various nonsteroidal antiinflammatory drugs (NSAIDs) have been received over the years by the Voluntary Adverse Reaction Reporting System, and some case reports have been published. Based on Inman's estimate of 22 deaths from blood dyscrasia per million patients (2), and FDA estimates of 16 deaths per million (3), it has been recommended that phenylbutazone is "not for initial use" for any condition. Its label contains strong warning statements, and oxyphenbutazone has been voluntarily withdrawn from the market by its major manufacturer.
To investigate the problem, the IAAA study used a different approach. For 4 years, 40 investigators in 7 countries monitored 300 hospitals that served a total population of 22.3 million, and this provided almost 90 million person-years of experience. Unexplained severe selective neutropenia (granulocytes <500/mm3) was identified in 422 cases, and aplastic anemia (leukocytes s3,500/mm3, platelets s50,000/mm3, hemoglobin 5 10 gm/dl, and reticulocytes s30,000/mm3) in 168 cases at the various hospitals. Aplastic anemia was confirmed by bone marrow examination and evaluation by a committee of hematologists. The overall annual incidence of agran-Harold E. Paulus, MD, American Rheumatism Association Liaison to the FDA Advisory Committee,