Diarrhea and angiotensin II receptor blockers: Is there any difference between the different drugs?

Diarrhea is an adverse drug reaction (ADR) widely reported with olmesartan, an angiotensin II receptor blocker (ARB). Isolated case reports described this ADR with other ARBs. The present study was performed to investigate if, among the different ARBs, some drugs are more at risk of diarrhea than others. Using VigiBase®, the WHO pharmacovigilance database, we performed a disproportionality analysis (case/noncase study). Cases were reports with the MedDRA PT term « diarrhea » and noncases all other reports registered during the same period in Vigibase® from April 6, 1995 to December 31, 2020. After comparison of ARBs and angiotensin converting enzyme inhibitors (ACEIs), the main analysis was a comparison of the diarrhea reporting risk between each ARB and the seven other ARBs. Results are reported as reporting odds ratio (ROR) adjusted on age, gender, exposure to antihypertensive, and antidiabetic drugs with their 95% confidence interval. Among the 22,429,334 deduplicated reports registered in VigiBase® during the study period, 73,507 involved ARBs, including 2119 diarrhea. The reporting risk of diarrhea was higher with ARBs than with ACEIs (ROR = 2.06 (1.55–2.17)). Diarrhea with ARBs mainly occurred in females with a mean age of 65 years. After exclusion of olmesartan (to minimize a notoriety bias), two ARBs were significantly associated with diarrhea: eprosartan (ROR = 1.93 (1.32–2.72) and telmisartan (ROR = 1.41 (1.23–1.62) but not the six others. The present study found first that diarrhea is more frequently reported with ARBs than with ACEIs and second that the risk of diarrhea differs according to the different ARBs. Diarrhea with ARBs is not a class effect.