Adverse event profiles of 5-fluorouracil and capecitabine: data mining of the public version of the FDA Adverse Event Reporting System, AERS, and reproducibility of clinical observations.
OBJECTIVE
The safety profiles of oral fluoropyrimidines were compared with 5-fluorouracil (5-FU) using adverse event reports (AERs) submitted to the Adverse Event Reporting System, AERS, of the US Food and Drug Administration (FDA).


METHODS
After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving 5-FU and oral fluoropyrimidines were analyzed. Standardized official pharmacovigilance tools were used for the quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean.


RESULTS
Based on 22,017,956 co-occurrences, i.e., drug-adverse event pairs, found in 1,644,220 AERs from 2004 to 2009, it was suggested that leukopenia, neutropenia, and thrombocytopenia were more frequently accompanied by the use of 5-FU than capecitabine, whereas diarrhea, nausea, vomiting, and hand-foot syndrome were more frequently associated with capecitabine. The total number of co-occurrences was not large enough to compare tegafur, tegafur-uracil (UFT), tegafur-gimeracil-oteracil potassium (S-1), or doxifluridine to 5-FU.


CONCLUSIONS
The results obtained herein were consistent with clinical observations, suggesting the usefulness of the FDA's AERS database and data mining methods used, but the number of co-occurrences is an important factor in signal detection.
Center for Integrative Education in Pharmacy and Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
Kaori
K
Kadoyama
Ikuya
I
Miki
Takao
T
Tamura
J B
JB
Brown
Toshiyuki
T
Sakaeda
Yasushi
Y
Okuno
D016907:Adverse Drug Reaction Reporting Systems; D000069287:Capecitabine; D057225:Data Mining; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003967:Diarrhea / Q000139:chemically induced; D005472:Fluorouracil / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D060831:Hand-Foot Syndrome; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D015203:Reproducibility of Results; D013921:Thrombocytopenia / Q000139:chemically induced; D014481:United States; D014486:United States Food and Drug Administration; D014839:Vomiting / Q000139:chemically induced
D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil