Spontaneous reporting of adverse reactions related to proton pump inhibitors

Background: Proton pump inhibitors (PPIs) are widely prescribed in all age groups, and their use is increasing. However, their safety profile has been frequently questioned. Aims: The aim of this study was to analyze the characteristics of PPI-related adverse drug reactions (ADRs) reported to the Italian spontaneous reporting system (SRS) database and relative to an Italian region (Sicily). Methods: A 20-year observational, retrospective study was conducted, evaluating PPI-related ADR reports from Sicily between January 1st, 2001, and June 30th, 2021. The factors associated with ADR seriousness were investigated. Results: A total of 148 spontaneous reports of ADRs related to PPIs were analyzed. Lansoprazole was the drug with the highest number of associated reports (30.87%). The most frequently reported ADRs were cutaneous (24.56%) and/or gastrointestinal manifestations (18.10%), the latter especially in the case of lansoprazole-related ADRs (p<0.006). The great majority of ADR reports were relative to on-label prescriptions. Serious ADRs were 39 (26.35%). Serious ADRs were more common in reports including omeprazole than in reports containing other PPIs (p<0.008) and in reports presenting PPIs combined with other drugs than in reports with PPI single therapies (p<0.001). Conclusion: Most PPI-related ADRs are non-serious. Omeprazole and combination therapy seem to be associated with ADR seriousness.