Syndrome of inappropriate antidiuretic hormone secretion is associated with different proton pump inhibitor use: a pharmacovigilance study

Abstract

Aim The objective of this study was to evaluate the reported associations between the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and a variety of proton pump inhibitors (PPI) through analysis of the reports extracted from the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods FAERS reports from January 2004 to March 2020 were used to conduct disproportionality and Bayesian analyses. The definition of SIADH relied on the preferred terms provided by the Medical Dictionary for Regulatory Activities. The time to onset, mortality, and hospitalization rates of PPI-related SIADH were also investigated. Results The study identified a total of 273 reports of PPI-associated SIADH, which appeared to influence more elderly than middle-aged patients (71.1% vs. 12.5%). Women were more affected than men (48.7% vs. 41.8%). Rabeprazole had a stronger SIADH association than other PPIs based on the highest reporting odds ratio (reporting odds ratio = 13.3, 95% confidence interval (CI) = 7.2, 24.9), proportional reporting ratio (proportional reporting ratio = 13.3, χ2 = 113.7), and empirical Bayes geometric mean (empirical Bayes geometric mean = 13.3, 95% CI = 7.9). The median time to SIADH onset was 22 (interquartile range 6–692) days after PPI administration. PPI-associated SIADH generally led to a 2.95% fatality rate and a 79.7% hospitalization rate. The highest hospitalization death rate occurred in esomeprazole (91.2%). Conclusion According to our findings, more attention should be paid to SIADH within the first several months after the administration of PPIs. For women older than 65 years, dexlansoprazole may reduce the incidence of PPI-associated SIADH. Nonetheless, larger epidemiological studies are suggested to verify this conclusion.

The Impact of Sex on the Response to Proton Pump Inhibitor Treatment

“…Several gender differences in the adverse reactions to PPIs have been reported. A recent study in China demonstrated that women were more likely to develop the PPI-related syndrome of inappropriate antidiuretic secretion (SIADH) [86]. However, the risk of PPI-associated hypomagnesemia was higher in males and in the elderly population [85].…”