Int J Med Sci 2012; 9(1):33-39. doi:10.7150/ijms.9.33
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
1. Center for Integrative Education in Pharmacy and Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
2. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
3. Department of Systems Biosciences for Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
4. Kyoto Constella Technologies Co., Ltd., Kyoto 604-8156, Japan.
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.
Conclusion: 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.
Keywords: adverse events, AERS, 5-fluorouracil, capecitabine, pharmacovigilance.
Kadoyama K, Miki I, Tamura T, Brown J, Sakaeda T, Okuno Y. 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. Int J Med Sci 2012; 9(1):33-39. doi:10.7150/ijms.9.33. Available from http://www.medsci.org/v09p0033.htm