Side Effects Research on PPIs

Kidney Disease, Injury, and Failure

  • A study in the journal Kidney International found that long-term use could lead to “silent” kidney damage. Researchers followed up 125,000 patients over five years (2017).
  • A study in the Journal of American Nephrology found that long-term users were 28% more likely to suffer from CKD and 95% more likely to experience kidney failure (2016).
  • A different study in the journal JAMA Internal Medicine associated long-term use with a 20%–50% higher chance of developing CKD (2016).

Clostridium Difficile and Pneumonia Infections

  • The FDA put out a safety communication stating that PPI use can increase the chances of C. difficile diarrhea (2012). Additionally, the agency required some manufacturers to add a warning regarding the risk to their labels in 2014.
  • Research published in the BMJ journal Gut compared twins (2015). One twin took PPIs while the other did not and found that the twin taking the drug had far more bacteria that can cause infections than the twin who did not take the drug.

Hip, Wrist, and Spinal Fractures

  • A study published in JAMA in 2006 concluded that long-term PPI therapy, particularly at high doses, is associated with an increased risk of hip fracture.
  • Several studies since 2006 have linked such use to bone fractures. Evidence suggests the drugs decrease bone density and increase the risk of osteoporosis.

Esophageal and Gastric Cancer

  • A study in Cancer Epidemiology, where researchers in Sweden reviewed seven years of medical records, found that PPI use could cause esophageal cancer in certain patients (2018).
  • A study published in the journal Gut found that taking PPIs could double the risk of getting gastric cancer and the risk increased with extended drug intake (2017).
  • The FDA required a gastric malignancy warning for drug labels (2017).

Heart Attacks and Strokes

  • A study by researchers at the Stanford University School of Medicine published in PLOS One found that medications could increase the risk of heart attacks by 16 to 20 percent (2015).
  • The FDA added a warning to the drug labels regarding the risk of low magnesium levels (hypomagnesemia) (2011). Low magnesium levels can cause an irregular heartbeat (arrhythmias). However, patients may not always exhibit symptoms.

Risks for Children, Infants, and Pregnant Women

  • A study found a childhood fracture risk with PPIs (2017). Researchers included 874,000 American children and found that those who took the medications before their first birthday had a 22% higher risk of childhood bone fractures. PPIs are not approved for infants younger than one month of age.