S1163 Drug-Diarrhea Associations Among Common Prescription Medications: An Analysis of the 2005-2010 NHANES Data

Introduction: In clinical trials of medications, diarrhea is a frequently reported adverse effect. However, exactly which medications are associated with an increased risk of diarrhea in the population with routine real-world use is understudied. A greater understanding of this risk may help clinicians identify medication-related contributors to diarrhea. In this study, we used a data-driven approach in a nationally representative data sample to investigate which commonly prescribed drugs are associated with diarrhea. Methods: This study used the 2005-2010 cycles of the National Health and Nutrition Examination Survey (NHANES), which included the bowel health questionnaire. We investigated all medications that were taken by at least 200 participants. Diarrhea was defined based on the survey question regarding the most common stool type as Bristol Stool Form Scale 6 or 7. For each of these medications, we used a survey-adjusted logistic regression model to test the association of that medication with diarrhea. We controlled for multiple comparisons using false-discovery rate adjustment. Results: The final sample size was 13,722 participants. Fifty medications were taken by at least 200 participants and included in the analysis. The estimated prevalence of diarrhea as defined by self-reported Bristol Stool Scale 6 or 7 was 6.6% (95% CI 6.1-7.1%). Three medications were found to have an FDR-adjusted P-value (q) less than 0.05: metformin, ranitidine, and pantoprazole. Metformin was associated with increased odds of diarrhea (odds ratio [OR] 1.87, 95% CI 1.44-2.42, P = 2.1e-5, q = 1.1e-3). Similar associations were observed for ranitidine (OR 2.2, 95% CI 1.4-3.5, P = 1.0e-3, q = 0.027) and pantoprazole (OR 2.6, 95% CI 1.4-4.8, P = 2.7e-3, q = 0.046). Conclusion: In this study, we found that metformin, ranitidine, and pantoprazole were associated with diarrhea. While metformin and pantoprazole are known to frequently cause diarrhea, ranitidine, though now discontinued in the United States, is less frequently recognized as a contributor to diarrhea risk, and corroborates that gastric acid reducing agents as a class may have a propensity for causing diarrhea. However, any causal interpretation of these findings is limited by confounding from medication indication. Future work will investigate how polypharmacy and drug interactions influence diarrhea risk.