Evaluation of case reports of aplastic anemia among patients treated with felbamate.
OBJECTIVE
Felbamate (FBM) is a new antiepileptic drug (AED) that is often effective in seizure disorders refractory to other treatments; its use has been greatly restricted after cases of aplastic anemia were reported. To elucidate the putative association between FBM and aplastic anemia, we made a detailed evaluation of the first 31 reports.


METHODS
Hematologic review according to the criteria of the International Agranulocytosis and Aplastic Anemia Study (IAAAS) confirmed 23 cases (74%) as aplastic anemia; FBM was judged to be the only plausible cause for three; confounding (mostly by other drugs) was considered possible, but FBM remained the most likely cause for 11; and there was at least one other plausible cause for 9.


RESULTS
Using a denominator from sales data of 110,000 persons exposed and a numerator of the cases for which FBM was considered the only plausible cause, we established a lower limit of incidence of 27 cases of aplastic anemia per million users as compared with the general population rate of 2.0 per million per year. With all confirmed cases used as the numerator, the upper limit of incidence was 209 per million. The 'most probable" incidence was estimated to be 127 per million.


CONCLUSIONS
Intensive, systematic investigation can maximize the utility of case reports for assessing risks of newly released drugs. The present evaluation confirmed an association between FBM and aplastic anemia; however, confounding was significant for most cases and there was a tenfold range in the "best case" and "worst case" incidence estimates among users.
Kaufman
D W
DW
Slone Epidemiology Unit, Boston University School of Medicine, Brookline, Massachusetts 02146, USA.
Kelly
J P
JP
Anderson
T
T
Harmon
D C
DC
Shapiro
S
S
D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data; D000741:Anemia, Aplastic / Q000139:chemically induced* / Q000453:epidemiology; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D015984:Causality; D015986:Confounding Factors, Epidemiologic; D004827:Epilepsy / Q000188:drug therapy*; D000078328:Felbamate; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008499:Medical Records / Q000706:statistics & numerical data; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000009:adverse effects* / Q000627:therapeutic use; D018570:Risk Assessment; D014481:United States / Q000453:epidemiology; D014486:United States Food and Drug Administration
D000927:Anticonvulsants; D048448:Phenylcarbamates; D011409:Propylene Glycols; D000078328:Felbamate