Proton pump inhibitor therapy and potential long-term harm

  title={Proton pump inhibitor therapy and potential long-term harm},
  author={Vito Domenico Corleto and Stefano Festa and Emilio di Giulio and Bruno Annibale},
  journal={Current Opinion in Endocrinology \& Diabetes and Obesity},
Purpose of reviewThis review summarizes the recent literature on the potential side-effects of proton pump inhibitors (PPIs) and known interactions with the metabolism/absorption of other drugs. Recent findingsData confirm that PPIs are a very well tolerated drug class. Their high safety, efficacy and wide distribution lead to overuse, inappropriate dosage or excessive duration of treatment. Despite the absorption of micronutrients or other plausible effects on the development of bacterial… 

Side effects of long-term use of proton pump inhibitors: practical considerations.

The most important and ascertained side effects of long-term use of PPIs are discussed, and practical considerations for their clinical management are provided.

Proton pump inhibitors: Risks of long‐term use

The most recent literature regarding these adverse effects and their association with long‐term proton pump inhibitor treatment is reviewed, and the mechanisms through which these possible complications might develop are discussed.

Proton pump inhibitor use for 12 months is not associated with changes in serum magnesium levels: a prospective open label comparative study.

Stable serum magnesium levels were demonstrated after 12 months and no association between PPI use and risk of hypomagnesemia was shown in the general population; nevertheless, further research is required before recommending any serum calcium and PTH level monitoring in patients initiated on long-term PPI therapy.

Pharmacokinetic evaluation of esomeprazole for the treatment of gastroesophageal reflux disease

Clinical studies on the pharmacokinetics and pharmacodynamics of esomeprazole as well as on its clinical efficacy to manage patients with GERD are explored, finding some patients may report better symptom control when treated with a specific PPI rather than with others.

Safety of proton pump inhibitors and risk of gastric cancers: review of literature and pathophysiological mechanisms

In pernicious anemia and chronic gastritis, clinicians should be aware of potential increased risk of gastric NET development with chronic PPI use in these patients, and Eradication status of H. pylori prior to commencing long-term PPI therapy should be established to reduce the risk of severe atrophic gastritis and development of Gastric dysplasia.

Esomeprazole use is independently associated with significant reduction of BMD: 1-year prospective comparative safety study of four proton pump inhibitors

Considering the widespread use of PPIs, BMD screening should be considered in the case of prolonged PPI use, and esomeprazole was independently associated with significant reduction of BMD, whereas omeprazole had no effects on BMD.

Does the use of proton pump inhibitors increase the risk of hypomagnesemia

A definitive conclusion could not be drawn on the relationship between the exposure to PPI and the incidence of hypomagnesemia, and a dose-response analysis may be required.

Is there a correlation between hypomagnesemia linked to long-term proton pump inhibitor use and the active agent?

It was concluded that hypomagnesemia linked to PPI use is associated with the type of PPI, and while patients using rabeprazole had the lowest rates, those using omeprazoles had significantly higher rates of hypomgnesemia.

Potential Cardiovascular Risks of Proton Pump Inhibitors in the General Population.

The possible cardiovascular risks in PPI users with no history of cardiovascular diseases are summarized and possible biological mechanisms are discussed.

Meta-analysis: proton pump inhibitors moderately increase the risk of small intestinal bacterial overgrowth

The meta-analysis suggests that the use of PPI moderately increases the risk of SIBO, thereby highlighting the need for appropriate prescribing of PPIs.



Increased incidence of small intestinal bacterial overgrowth during proton pump inhibitor therapy.

Association of Long-Term Proton Pump Inhibitor Therapy with Bone Fractures and Effects on Absorption of Calcium, Vitamin B12, Iron, and Magnesium

Significant results of several studies support the conclusion that long-term adverse effects on these processes can have important clinical implications, and studies of the effects of chronic PPI use on absorption of VB12, iron, and magnesium are examined.

Proton pump inhibitor use and the risk of small intestinal bacterial overgrowth: a meta-analysis.

  • Wai-Kit LoWalter Wai-Yip Chan
  • Medicine
    Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
  • 2013

Association Between Proton Pump Inhibitor Use and Anemia: A Retrospective Cohort Study

Among adult patients receiving chronic PPI therapy, there is a significant decrease in hematologic indices from baseline, and PPI users had significant decreases in mean hemoglobin and hematocrit compared with matched controls.

Long-term proton pump inhibitor use and gastrointestinal cancer

It is recommended that patients being considered for long-term proton pump inhibitor therapy should be tested for H. pylori infection and, if present, this pathogen should be eradicated.

Systematic Review of the Risk of Enteric Infection in Patients Taking Acid Suppression

There is an association between acid suppression and an increased risk of enteric infection and further prospective studies on patients taking long-term acid suppression are needed to establish whether this association is causal.

Meta-analyses: does long-term PPI use increase the risk of gastric premalignant lesions?

Maintenance PPIs did not have an association with increased gastric atrophic changes or ECL-cell hyperplasia for at least three years in RCTs, according to a systematic review of the available literature.

Risk of Clostridium difficile Infection With Acid Suppressing Drugs and Antibiotics: Meta-Analysis

Despite the substantial statistical and clinical heterogeneity, the findings indicate a probable association between PPI use and incident and recurrent CDI, which is further increased by concomitant use of antibiotics and PPI, whereas H2RAs may be less harmful.

Proton Pump Inhibitors and Risk of Fracture: A Systematic Review and Meta-Analysis of Observational Studies

A systematic review and meta-analysis of controlled observational studies found a modest association between PPI use and increased risk of hip and vertebral fractures, but no evidence of duration effect in subgroup analysis.

Association between proton pump inhibitor therapy and Clostridium difficile infection in a meta-analysis.

  • A. DeshpandeC. Pant Adrian V. Hernández
  • Medicine, Biology
    Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
  • 2012