In summary, the results of this study suggest that disproportionality analysis using empirical Bayes data mining is a promising tool for investigating the clinical relevance of potential drug interactions. By studying drugs with well-known safety profiles, we were able to correlate the results with the well-established pharmacologic effects of these drugs and verify the reliability of the approach. The predictive value of this method will depend on many factors, including the seriousness of the adverse event, which may affect how frequently it is reported. Hence, results must be interpreted with caution, and if possible, validated with case review. Further confirmation of a cause-effect relationship between drug combination and AE pairs would require independent testing using clinical pharmacology studies or clinical trials.