Long-term safety concerns with proton pump inhibitors

Am J Med. 2009 Oct;122(10):896-903. doi: 10.1016/j.amjmed.2009.04.014.


Proton pump inhibitors (PPIs) are among the most widely prescribed medications worldwide. Their use has resulted in dramatic improvements in treatment of peptic ulcer disease and gastroesophageal reflux disease. Despite an acceptable safety profile, mounting data demonstrate concerns about the long-term use of PPIs. To provide a comprehensive review regarding the concerns of long-term PPI use, a literature search was performed to identify pertinent original and review articles. Despite study shortcomings, the collective body of information overwhelmingly suggests an increased risk of infectious complications and nutritional deficiencies. Data regarding any increased risk in gastric or colon malignancy are less convincing. PPIs have revolutionized the management and complications of acid-related disorders with a high margin of safety; however, with the data available, efforts to reduce the dosing of or discontinue the use of PPIs must be reassessed frequently.

Publication types

  • Review

MeSH terms

  • Anti-Ulcer Agents / adverse effects*
  • Anti-Ulcer Agents / therapeutic use
  • Calcium / deficiency
  • Case-Control Studies
  • Colonic Neoplasms / chemically induced
  • Colonic Neoplasms / epidemiology
  • Deficiency Diseases / chemically induced
  • Deficiency Diseases / epidemiology
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Gastritis, Atrophic / chemically induced
  • Gastritis, Atrophic / epidemiology
  • Gastroesophageal Reflux / diagnosis
  • Gastroesophageal Reflux / drug therapy*
  • Humans
  • Incidence
  • Iron Deficiencies
  • Long-Term Care
  • Male
  • Monitoring, Physiologic / methods
  • Osteoporosis / chemically induced
  • Osteoporosis / epidemiology
  • Proton Pump Inhibitors / adverse effects*
  • Proton Pump Inhibitors / therapeutic use
  • Risk Assessment
  • Safety Management
  • Stomach Neoplasms / chemically induced
  • Stomach Neoplasms / epidemiology
  • Time Factors


  • Anti-Ulcer Agents
  • Proton Pump Inhibitors
  • Calcium