[Adverse effects of proton pump inhibitors: should we worry about long-term exposure?]

Rev Med Interne. 2012 Aug;33(8):439-45. doi: 10.1016/j.revmed.2011.12.011. Epub 2012 Jan 27.
[Article in French]


Long-term treatment with proton pump inhibitors (PPI) is becoming more prevalent. Although they are well tolerated in the short term, serious concerns about long-term use have arisen. Recent data suggest that the latter is associated with an increased risk for osteoporotic fracture (especially vertebral), Clostridium difficile infection and rebound acid hypersecretion after treatment discontinuation. Acute interstitial nephritis is rare but may progress to chronic renal failure. An increased risk of community-acquired pneumonia has not been established in the general population and seems limited to the most vulnerable patients. Consistent data are still missing to correctly assess the risk of iron deficiency, vitamin B12 deficiency or hypomagnesaemia and the risk of digestive malignant diseases, despite the pathophysiological basis that exists concerning gastric malignancy. Many drug interactions can occur on long-term treatment, including some that imply the cytochrome P450 enzymes. Finally, the risk-benefit balance for a chronic PPI use in children seems unfavorable in most cases.

Publication types

  • Evaluation Study
  • Review

MeSH terms

  • Adenocarcinoma / chemically induced
  • Adenocarcinoma / epidemiology
  • Anti-Ulcer Agents / administration & dosage
  • Anti-Ulcer Agents / adverse effects
  • Anti-Ulcer Agents / therapeutic use
  • Drug Interactions
  • Gastrointestinal Neoplasms / chemically induced
  • Gastrointestinal Neoplasms / epidemiology
  • Humans
  • Infections / chemically induced
  • Infections / epidemiology
  • Nephritis / chemically induced
  • Nephritis / epidemiology
  • Proton Pump Inhibitors / administration & dosage
  • Proton Pump Inhibitors / adverse effects*
  • Proton Pump Inhibitors / therapeutic use
  • Risk Assessment
  • Time Factors
  • Vitamin B 12 Deficiency / chemically induced
  • Vitamin B 12 Deficiency / epidemiology


  • Anti-Ulcer Agents
  • Proton Pump Inhibitors