418 A Review of Timelines and Reporters of Adverse Events From Proton Pump Inhibitors (PPIs) That Are Conveyed to the United States Food and Drug Administration Adverse Event Reporting System (FAERS).

Abstract

INTRODUCTION: Recent publications have described potential PPI-associated adverse events (AEs) including cardiovascular disease (CVD), cerebrovascular accidents (CVA) and renal disease (acute interstitial nephritis and CKD). There is public interest and potential for lawsuits for these and other PPI-related AEs. The FAERS is a database of voluntarily reported AEs used for post-marketing surveillance of medications. The aim of this study is to analyze reports of all PPI-associated-AEs to FAERS, focusing on reporter sources. This permits an understanding of the effect of published high-profile PPI-associated AEs on FDA drug surveillance. METHODS: A total of 9,144,290 FAERS reports from January 2013 to December 2018 were examined. Analysis of all Primary PPI-related AEs were included (C. difficile, microscopic colitis, atrophic gastritis, hypergastrinemia, hypomagnesemia, hypocalcemia, hypokalemia, hypophosphatemia, vitamin malabsorption, pneumonia, CVD, CVA, renal disease, drug-induced lupus, and dementia). AEs were defined by MedDRA terminology. All reports were categorized according to reporter source (physicians, pharmacists, other health care professionals, consumers, and lawyers). RESULTS: Until 2018, overall reporting of PPI-related AEs generally showed steady changes over time. In 2015 there were 7,024 reports for all PPI-related AEs, in 2016, there were 8,043, and in 2017, there were 7,682. Notably, in 2018, reports for all PPI-related AEs spiked to 14,607. For specific AEs, reports for renal disease and CVD from consumers showed marked increases. In 2015 consumers reported 427 CVD cases and 494 renal cases, while consumers reported 627 CVD cases and 1,155 renal cases in 2018 (Figure 1). Reports for lawyers and physicians for CVD and renal disease both increased between 2015 and 2018. Physicians had an increase from 368 to 503 cases of CVD (36.7% increase) and from 676 cases to 1,112 of renal disease (64.5% increase), while lawyers had an increase of 49 cases of CVD to 99 cases of CVD (102% increase) and increase of 4 cases to 974 of renal disease (24,250% increase). This resulted in a rise in percentage of total reports from lawyers (Figures 2 and 3). CONCLUSION: Consumers are increasing reporting of CVD and renal disease associated with PPI use. The rapid increase in reports of PPI-associated CVD and especially renal disease by lawyers suggests that lawyers are a potential source of interference on pharmacovigilance.