Online citations, reference lists, and bibliographies.

Clinical Implications Of Emerging Data On The Safety Of Proton Pump Inhibitors

Felice Schnoll-Sussman, Philip O Katz
Published 2017 · Medicine
Cite This
Download PDF
Analyze on Scholarcy
Opinion statementProton pump inhibitors (PPI) are among the safest class of drugs used by all care providers, including gastroenterologists. They are the mainstay in treatment of acid-related disease, in particular, gastroesophageal reflux disease. Without them, many patients would experience a major decrement in their quality of life. However, no drug is without side effects or adverse events. In the past decade, numerous reports, principally case control studies and meta-analyses, have raised questions about important adverse events related to the use of PPIs. This has affected not only physicians’ prescribing habits but patients’ concerns about using these medications, particularly long term. Several FDA warnings are listed including those related to long bone fractures, interaction with clopidogrel, enteric infections, and hypomagnesaemia. More recently, concerns regarding PPIs and cardiovascular events have resurfaced as have issues related to kidney disease and dementia. The methodology of these studies allows us to find an association with these events but does not provide us with sufficient evidence to determine causality. In general, the findings of the available studies do not fit with our clinical experience nor is the magnitude of the association sufficient to result in a major change in our practice. Nevertheless, the recent literature has resulted in our careful reevaluation of PPI use across both FDA indications and in general. This article will critically review the literature regarding potential PPI adverse events and attempt to place them in perspective for the practicing physician.
This paper references
Proton-pump inhibitor use is not associated with osteoporosis or accelerated bone mineral density loss.
L. Targownik (2010)
A randomized, 2-period, crossover design study to assess the effects of dexlansoprazole, lansoprazole, esomeprazole, and omeprazole on the steady-state pharmacokinetics and pharmacodynamics of clopidogrel in healthy volunteers.
Andrew L Frelinger (2012)
Colonization With Toxinogenic C. difficile Upon Hospital Admission, and Risk of Infection: A Systematic Review and Meta-Analysis
Ioannis M. Zacharioudakis (2015)
Risk factors for indigenous Campylobacter jejuni and Campylobacter coli infections in The Netherlands: a case-control study.
Y. Doorduyn (2010)
Vegetative Clostridium difficile Survives in Room Air on Moist Surfaces and in Gastric Contents with Reduced Acidity: a Potential Mechanism To Explain the Association between Proton Pump Inhibitors and C. difficile-Associated Diarrhea?
Robin L P Jump (2007)
Long-term safety concerns with proton pump inhibitors.
Tauseef Ali (2009)
Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities.
Xue-qing Li (2004)
Long-term use of proton pump inhibitors and vitamin B12 status in elderly individuals.
Wendy.PJ. den Elzen (2008)
Systematic review : the effects of long - term proton pump inhibitor use on serum gastrin levels and gastric histol
L Lundell (2015)
Proton pump inhibitors and gastric neoplasia
E. Kuipers (2006)
Proton Pump Inhibitors and Risk of Fracture: A Systematic Review and Meta-Analysis of Observational Studies
S. Ngamruengphong (2011)
Proton pump inhibitors and histamine-2 receptor antagonists are associated with hip fractures among at-risk patients.
Douglas A. Corley (2010)
Prolonged use of a proton pump inhibitor reduces microbial diversity: implications for Clostridium difficile susceptibility
Charlie T Seto (2014)
Proton - pump inhibitorsareassociatedwithincreasedcardiovascularrisk independent of clopidogrel use : a nationwide cohort study
AhlehoffO CharlotM (2010)
Effects of proton pump inhibitors on calcium carbonate absorption in women: a randomized crossover trial.
M. B. O'Connell (2005)
Comparison of 24-h control of gastric acidity by three different dosages of pantoprazole in patients with duodenal ulcer.
Vincenzo Savarino (1998)
Proton pump inhibitor use represents an independent risk factor for myocardial infarction.
Chia-Jen Shih (2014)
The Relationship Between Proton Pump Inhibitor Use and Longitudinal Change in Bone Mineral Density: A Population-Based From the Canadian Multicentre Osteoporosis Study (CaMos)
L. Targownik (2012)
Do Proton Pump Inhibitors Decrease Calcium Absorption?
Karen Ejersbo Hansen (2010)
Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women: results from the Women's Health Initiative.
S. Gray (2010)
Systematic Review of the Risk of Enteric Infection in Patients Taking Acid Suppression
J. Leonard (2007)
Effect of long-term gastric acid suppressive therapy on serum vitamin B12 levels in patients with Zollinger-Ellison syndrome.
B Termanini (1998)
Prevention and Self-Treatment of Traveler's Diarrhea
D. Diemert (2006)
Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects.
J. Hulot (2006)
Out-of-hospital use of proton pump inhibitors and hypomagnesemia at hospital admission: a nested case-control study.
Ioannis Koulouridis (2013)
Vitamin B12 deficiency in hypersecretors during long-term acid suppression with proton pump inhibitors.
B. Hirschowitz (2008)
Clostridium difficile-Associated Diarrhea and Proton Pump Inhibitor Therapy: A Meta-Analysis
Sailajah Janarthanan (2012)
Proton pump inhibitors and vascular function: A prospective cross-over pilot study
Yohannes T. Ghebremariam (2015)
Risk factors for Salmonella Enteritidis and Typhimurium (DT104 and non-DT104) infections in The Netherlands: predominant roles for raw eggs in Enteritidis and sandboxes in Typhimurium infections.
Y. Doorduyn (2006)
Incidence of cardiovascular events and gastrointestinal bleeding in patients receiving clopidogrel with and without proton pump inhibitors: an updated meta-analysis
R. Cardoso (2015)
Systematic review: the use of proton pump inhibitors and increased susceptibility to enteric infection
Kenneth R. Devault (2012)
Association between use of proton pump inhibitors and non-typhoidal salmonellosis identified following investigation into an outbreak of Salmonella Mikawasima in the UK, 2013.
Richard Freeman (2016)
Association of Proton Pump Inhibitors With Risk of Dementia: A Pharmacoepidemiological Claims Data Analysis.
Willy Gomm (2016)
Omeprazole and bafilomycin, two proton pump inhibitors: differentiation of their effects on gastric, kidney and bone H(+)-translocating ATPases.
J. P. Mattsson (1991)
Systematic review: the effects of long-term proton pump inhibitor use on serum gastrin levels and gastric histology.
L. Lundell (2015)
Unexpected Effect of Proton Pump Inhibitors: Elevation of the Cardiovascular Risk Factor Asymmetric Dimethylarginine
Yohannes T. Ghebremariam (2013)
Clopidogrel with or without omeprazole in coronary artery disease.
Deepak L. Bhatt (2010)
Effect of Increasing Esomeprazole and Pantoprazole Doses on Acid Control in Patients with Symptoms of Gastro-Oesophageal Reflux Disease
C. Wilder-Smith (2008)
Gastric acid, calcium absorption, and their impact on bone health.
Sascha Kopic (2013)
Systematic review with meta-analysis: post-infectious irritable bowel syndrome after travellers' diarrhoea.
Juliane Schwille-Kiuntke (2015)
Revising the link between proton-pump inhibitors and risk of acute myocardial infarction—a case-crossover analysis
Aleksandra Turkiewicz (2014)
Esomeprazole with clopidogrel reduces peptic ulcer recurrence, compared with clopidogrel alone, in patients with atherosclerosis.
Ping-I Hsu (2011)
Proton-Pump Inhibitors Are Associated With Increased Cardiovascular Risk Independent of Clopidogrel Use
M. Charlot (2010)
Long-term proton pump inhibitor therapy and risk of hip fracture.
Yu-Xiao Yang (2006)
Proton Pump Inhibitors Alter Specific Taxa in the Human Gastrointestinal Microbiome: A Crossover Trial.
Daniel E Freedberg (2015)
Daytime intragastric acid control: post hoc analyses of esomeprazole 20 mg and over-the-counter proton-pump inhibitors
Philip O Katz (2015)
Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRD.
Yan Xie (2016)
Pathogenesis of Escherichia coli diarrhea.
H. DuPont (1971)
Risk of dementia in elderly patients with the use of proton pump inhibitors
B. Haenisch (2014)
Long-term safety of proton pump inhibitor therapy assessed under controlled, randomised clinical trial conditions: data from the SOPRAN and LOTUS studies.
Stephen E. A. Attwood (2015)
Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population
Nigam Haresh Shah (2015)
Prevention and treatment of traveler's diarrhea.
G. Juckett (1999)
parison of inhibitory effects of the proton pump - inhibiting drugs omeprazole , esomeprazole , lansoprazole , pantoprazole , and rabeprazole on human cytochrome P 450 activities
XQ Li (2004)
Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease.
Benjamin M. Lazarus (2016)
Proton pump inhibitors increase significantly the risk of Clostridium difficile infection in a low-endemicity, non-outbreak hospital setting.
Bruce R Dalton (2009)
Inhibiting gastric acid production does not affect intestinal calcium absorption in young, healthy individuals: a randomized, crossover, controlled clinical trial.
Matthew J Wright (2010)
Prevention and Treatment of Travelers' Diarrhea
H L DuPont (2010)
Proton-pump inhibitors and hypomagnesemic hypoparathyroidism.
M. Epstein (2006)

This paper is referenced by
Meta-analysis: proton pump inhibitors moderately increase the risk of small intestinal bacterial overgrowth
Tingting Su (2017)
Initial experience with a novel resection and plication (RAP) method for acid reflux: a pilot study
Petros C. Benias (2018)
Surgical management of gastroesophageal reflux disease in patients with systemic sclerosis
Jingliang Yan (2018)
Proton Pump Inhibitors Intake and Iron and Vitamin B12 Status: A Prospective Comparative Study with a Follow up of 12 Months
Hasime Qorraj-Bytyqi (2018)
Proton pump inhibitors and risk for recurrent ischemic events or death in outpatients with symptomatic artery disease.
Juan Francisco Sánchez Muñoz-Torrero (2019)
A qualitative synthesis of gastro-oesophageal reflux in bronchiectasis: Current understanding and future risk.
Melissa J McDonnell (2018)
Demographic and health-related predictors of proton pump inhibitor (PPI) use and association with chronic kidney disease (CKD) stage in NHANES population.
Radhika Devraj (2019)
Bowel symptoms in patients that receive proton pump inhibitors. Results of a multicenter survey in Mexico.
Max Schmulson (2019)
The relationship between proton pump inhibitors and renal disease
Carine Franco Morschel (2018)
Síntomas intestinales en pacientes que reciben inhibidores de bomba de protones (IBP). Resultados de una encuesta multicéntrica en México
Max Schmulson (2019)
Bowel symptoms in patients that receive proton pump inhibitors. Results of a multicenter survey in Mexico.
Max Schmulson (2019)
Role and safety of fundoplication in esophageal disease and dysmotility syndromes.
Charles T. Bakhos (2019)
Osteoporosis following heart transplantation and immunosuppressive therapy.
Eveline Löfdahl (2017)
Low gut microbiota diversity and dietary magnesium intake are associated with the development of PPI-induced hypomagnesemia.
Lisanne M M Gommers (2019)
Long-term Treatment With Proton Pump Inhibitors Is Effective in Children With Eosinophilic Esophagitis
Carolina Gutiérrez‐Junquera (2018)
PPI use and oesophageal cancer: What if the results are true?
Nele Brusselaers (2018)
Laparoscopic magnetic sphincter augmentation versus fundoplication for gastroesophageal reflux disease: systematic review and pooled analysis.
Nadia Guidozzi (2019)
Use of proton pump inhibitors and risk of ischemic events in the general population.
Manuela Casula (2018)
Systematic review and meta-analysis of adverse cardiovascular events associated with proton pump inhibitors used alone or in combination with antiplatelet agents
Nawal Farhat (2019)
The Influence of Antireflux Surgery on Esophageal Cancer Risk in England: National Population-based Cohort Study
Sheraz R Markar (2018)
Diagnosis and Management of Eosinophilic Esophagitis.
Jeffrey M. Wilson (2018)
Semantic Scholar Logo Some data provided by SemanticScholar