Adverse Effects of Long-Term Proton Pump Inhibitor Therapy

  title={Adverse Effects of Long-Term Proton Pump Inhibitor Therapy},
  author={Edward Sheen and George Triadafilopoulos},
  journal={Digestive Diseases and Sciences},
Proton pump inhibitors have an excellent safety profile and have become one of the most commonly prescribed class of drugs in primary and specialty care. Long-term, sometimes lifetime, use is becoming increasingly common, often without appropriate indications. This paper is a detailed review of the current evidence on this important topic, focusing on the potential adverse effects of long-term proton pump inhibitor use that have generated the greatest concern: B12 deficiency; iron deficiency… 

The Effects on Nutrition, Metabolism and Infection by Proton Pump Inhibitors: Unsafe Perspective

A detailed review of the evidence on the adverse effects of long-term PPI use that have developed the greatest concern; vitamin B12 deficiency, iron deficiency, impaired calcium absorption, bony fracture, hypomagnesemia, increased susceptibility to pneumonia and enteric infections is reviewed.

Indications and safety of proton pump inhibitor drug use in patients with cancer

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Assessment of retrospective observational investigations remains the only method to evaluate adverse events with any drug in general and, although the weaknesses of these studies are evident, the awareness of the reported associations with the medications analyzed is important for physicians in order to manage adequately their individual patients.

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Proton pump inhibitors: potential adverse effects

  • N. Abraham
  • Medicine, Biology
    Current opinion in gastroenterology
  • 2012
Strong data supporting risk of adverse events are lacking, however, exercise caution in the elderly and in patients with other risk factors for bone fractures or C. difficile infection, andribe PPI for robust indications only.

Nutritional consequences of long-term acid suppression; are they clinically important?

  • D. Johnson
  • Medicine
    Current opinion in gastroenterology
  • 2016
This review highlights the most recent information around these controversies and provides evidence summaries to help guide care providers in their care plans as well as discussions with patients.


A number of the studies are showing consistent results that support the conclusion that long-term adverse effects on these processes can have important clinical implications, as well as the studies of the effects of chronic PPI usage on VB12 calcium absorption which leads to neurologic disorders and osteoporosis.



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.

Pharmacokinetic Drug Interaction Profiles of Proton Pump Inhibitors

The potential for drug interactions should be taken into account when choosing a therapy for gastric acid-related disorders, especially for elderly patients in whom polypharmacy is common, or in those receiving a concomitant medication with a narrow therapeutic index.

Proton-Pump Inhibitor Use and the Risk for Community-Acquired Pneumonia

This large, nested casecontrol study involving adults in general practices in the United Kingdom found that current, long-term PPI use was not associated with increased risk for community-acquired pneumonia (CAP), and recently started PPI therapy was associated withIncreased risk.

Chronic proton pump inhibitor therapy and the risk of colorectal cancer.

Long-term proton pump inhibitor therapy at a regular dose is not associated with a significantly increased risk of colorectal cancer.

Long-term proton pump inhibitor therapy and risk of hip fracture.

Long-term PPI therapy, particularly at high doses, is associated with an increased risk of hip fracture.

Review article: potential gastrointestinal effects of long‐term acid suppression with proton pump inhibitors

This review examines the evidence for the development of adverse effects due to prolonged gastric acid suppression with proton pump inhibitors in patients with Helicobacter pylori infection and other potential areas of concern.

Proton pump inhibitors: an update of their clinical use and pharmacokinetics

  • S. ShiU. Klotz
  • Medicine, Biology
    European Journal of Clinical Pharmacology
  • 2008
This update of pharmacokinetic, pharmacodynamic, and clinical data will provide the necessary guide by which to select between the various PPIs that differ—based on pharmacodynamic assessments—in their relative potencies.

Proton pump inhibitors and histamine-2 receptor antagonists are associated with hip fractures among at-risk patients.

Use of drugs that inhibit gastric acid is associated with an increased risk of hip fracture; however, this association was only found among persons with at least one other risk factor for hip fracture.

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.