Diarrhoea with the Angiotensin Receptor Neprilysin Inhibitor sacubitril+valsartan: a pharmacovigilance study.

Abstract

PURPOSE\nDiarrhoea is an adverse drug reaction of the Angiotensin Receptor Neprilysin Inhibitor (ARNI) sacubitril+valsartan. It was also described with olmesartan and more recently with other angiotensin receptor blockers. The study was performed to compare diarrhoea reports in pharmacovigilance databases with sacubitril+valsartan and valsartan.\n\n\nMETHODS\nThe study used reports of diarrhoea with the ARNI sacubitril+valsartan registered, first in the French PharmacoVigilance Database (FPVD) and second, in Vigibase®, the WHO Global Individual Case Safety Report database. After description of the main characteristics disproportionality analyses were performed. Results are reported as Reporting Odds Ratios (ROR) with 95% Confidence Interval.\n\n\nRESULTS\nWe found 29 reports of diarrhoea with sacubitril+valsartan in the FPVD and 686 in Vigibase®. With sacubitril+valsartan, diarrhoea occurred more frequently in males around 70 years with a median delay of 3 days. With valsartan, diarrhoea occurred more frequently in females around 68 years with a median delay of 0.5 days. In the FPVD, a significant association was found with sacubitril+valsartan in comparison with valsartan alone before (ROR=8.78 (5.19-14.85)) and after (ROR=11.19 (5.89-21.25)) exclusion of concomitant drugs known to be associated with diarrhoea. A significant association was also found in Vigibase® after adjustment on age, sex, reporter and its location (ROR= 1.31 (1.14-1.50)).\n\n\nCONCLUSION\nDiarrhoea reported with sacubitril+valsartan has marked differences in gender, delay of occurrence and frequency of reporting in comparison with diarrhoea with valsartan. From a pharmacodynamic point of view, these results suggest a specific role of sacubitril in diarrhoea.