The Association between Ranitidine Use and Gastrointestinal Cancers

N-nitrosodimethylamine (NDMA) is a carcinogen in experimental animals. It has been classified a probable human carcinogen and has been found in ranitidine. This study sought to evaluate the association between ranitidine use and cancer of the gastrointestinal system. Events reported to the FDA Adverse Events Reporting System that were associated with the use of proton pump inhibitors (PPIs) and H2 antagonists were selected. Proportionate reporting ratios (PRRs) and associated 95% confidence intervals (CIs) were calculated to compare the proportion of all reported adverse events that were for gastrointestinal system cancers among adverse event reports for ranitidine to adverse event reports for other H2 antagonists. The proportion of adverse events for any gastrointestinal system cancer relative to all other events was elevated for ranitidine compared to PPIs and other H2 antagonists (PRR 3.66, 95% CI 3.19–4.20). Elevated and significant PRRs were observed for pharyngeal (PRR 9.24), esophageal (PRR 3.56), stomach (PRR 1.48), colorectal (PRR 16.31), liver (PRR 2.64), and pancreatic (PRR 2.18) cancers. The PRRs for anal (PRR 4.62) and gallbladder (PRR 4.62) cancer were also elevated though not statistically significant. In conjunction with a large body of epidemiologic and human and animal basic science research, the study results support the hypothesis that NDMA-contaminated ranitidine increases the risk of cancer and supports the withdrawal of these medications from the market.

Infant acid suppression use is associated with the development of eosinophilic esophagitis

Summary Eosinophilic esophagitis (EoE) is an esophageal allergic inflammatory disorder often presenting with infant/toddler gastroesophageal reflux symptoms refractory to treatment, including acid suppression trials with histamine H2 antagonists and proton pump inhibitors. We propose to evaluate the impact of infant acid suppressant exposure in EoE. Geisinger’s pediatric EoE cases were matched to controls (1:5 EoE case control ratio) using age, race, sex, and ages at other diagnoses of asthma, eczema, and environmental allergies, totaling 526 EoE cases and 2,630 controls. Comparisons between EoE cases and matched controls were tested with regard to rates of acid suppression use with H2 antagonists and PPIs during infancy. Our analyses found the use of acid suppression in infancy was positively associated with EoE: PPI (5.7% EoE cases vs. 1.6% controls; P < 0.0001), H2 antagonists (8.8% EoE cases vs. 4.5% controls; P < 0.0001). Additionally, analysis of EoE cases using acid suppression during infancy indicated a likelihood for the diagnosis with EoE at an earlier age. Early acid suppression use in infants is significantly associated with the diagnosis of EoE in childhood in this well-matched retrospective cohort study. The potential link warrants additional investigation. Our study further reinforces the evidence-based stewardship of acid suppressant use, especially in our most vulnerable populations.

Survey on the Prevalence of Intravenous Use of Proton Pump Inhibitors and H2-antagonists in Internal Medicine Ward

Background: Anti-acids drugs are commonly used for stress ulcer prophylaxis (SUP). Some inpatients receiving acid suppression therapy without risk factors for nosocomial upper gastrointestinal bleeding and this inappropriate usage increase time, costs and avoidable side effects such as hospital-acquired pneumonia. Purpose: This study was designed to evaluate the prevalence of stress ulcer prophylactic drugs use, the number of properly indicated administrations and prescription prevalence of intravenous use of proton pump inhibitors (PIPs) and H2-antagonists in preventing nosocomial gastrointestinal bleeding and pneumonia. Methods: This cross-sectional study was performed on 280 patients in two different time zone before and after implementing of guidelines for SUP usage on the medical service in January and March of 2014(pre-intervention period) and January and march of 2015 (post-intervention period). Indicated anti-acid therapy for stress ulcer prophylaxis was defined according to the 1999 American Society of Health-System Pharmacists (ASHP) guidelines for the use of SUP. The Patient’s data such as kind of stress ulcer prophylaxis drug, ICU admission and the indication of prophylaxis pre and post-intervention were collected. Data were analyzed by SPSS software using the Pearson Chi-square test and unpaired t-test. Results: There was no significant change in the administration of stress ulcer prophylaxis drugs in general, but anti-acid medications misused decreased from 63.6% to 55.2% after intervention. Conclusion: The use of anti-acids without proper indication had 11.4% fall. The IV administration had a dramatic decrease as opposed to PO anti-acids use, which had a significant effect on hospital financial costs. In the end, there was no significant change detected in the total use of SUP (stress ulcer prophylaxis).