A Quantitative Analysis of FDA Adverse Event Reports with Oral Bisphosphonates and Clostridium difficile.

Background: Studies have shown associations between Clostridium difficile infection (CDI) and non-antimicrobial medications including proton pump inhibitors, osteoporosis medications, and antidepressants.

Objectives: Our primary objective was to evaluate oral bisphosphonates and reported CDI adverse drug reactions in the United States using the Food and Drug Administration Adverse Event Reporting System data (FAERS).

Methods: We performed a disproportionality analysis evaluating the proportion of reports with bisphosphonates and CDI compared with other adverse drug reactions in the database. A relatively increased number of reports for a given adverse drug reaction (ADR) is termed a "signal." Four major measures of association are used to describe reports: reporting odds ratio, proportional reporting ratio, information component, and empirical Bayes geometric mean. Drugs with statistically significant safety signals were stratified by age (18-40, 41-65, and 65+ years) and gender.

Results: Alendronate had 0.4% (103/23,603) reports with CDI. There were 0.4% (16/3672) and 0.2% (17/7945) of reports for risedronate and ibandronate, respectively. Alendronate (Fosamax) was the only drug with a significant signal using all four calculation methods. For reports with gender available, alendronate CDI ADRs were more common for women (0.45% [93/20,586]) versus men (0.25% [4/1568]), and a signal was detected with all four methods. For reports with age available, there were limited alendronate reports for those 18-39 years of age, and CDI reports were present in 0.50% (27/5350) of cases of 40-64 years and 0.49% (42/8525) of cases aged 65 or older.

Conclusion: Alendronate was associated with a high number of CDI ADRs relative to other drugs in FAERS. This signal was strongest for women and those 40 years or older. This interesting finding should be interpreted with caution, and further research is warranted.