Side Effects of Proton Pump Inhibitors

Proton pump inhibitors (PPIs) are a group of drugs whose purpose it is to reduce stomach acid. They have been used to treat a wide of gastric acid-related illnesses for more than 30 years and are known to be safe and effective—so much so that they've largely supplanted H2 blockers as the drug of choice.

Girl taking medication holding a glass of water
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This is not to say that PPIs aren't without their challenges or limitations. While most of the side effects are mild and manageable, there are a number of adverse events which can occur with long-term use or overuse. These include problems with the absorption of minerals, changes in bone density, and an increased risk for certain chronic illnesses.

How Proton Pump Inhibitors Work

Proton pump inhibitors are commonly used to treat disorders like gastroesophageal reflux disease (GERD), peptic ulcers, and erosive esophagitis. Healthcare providers may prescribe using PPIs alone or in combination with antacids. They can also be used in combination with certain antibiotics when treating Helicobacter pylori (a bacteria commonly associated with recurring stomach ulcers).

PPIs work by binding to a cell on the wall of the stomach called the parietal cell whose purpose it is to produce hydrochloric acid (HCL). By doing so, the stomach is less able to secrete HCL, allowing ulcers to heal and reflux to subside.

PPIs differ from H2 blockers in that PPIs shut down the acid pumps while H2 blockers only block the signal that trigger acid production. Because of this, PPIs work for up to 24 hours and provide relief for up to 72 hours. H2 blockers, by contrast, work for 12 hours.

Types of Proton Pump Inhibitors

Generally speaking, one PPI doesn't differ all that much from others. They all have similar mechanisms of action and similar rates of effectiveness. Currently approved PPIs include:

  • Prilosec (omeprazole)
  • Prevacid (lansoprazole)
  • Protonix (pantoprazole)
  • Aciphex (rabeprazole)
  • Nexium (esomeprazole)
  • Dexilant (dexlansoprazole)

It's important to speak with your healthcare provider to ensure that the use of a PPI is appropriate.

Side Effects and Interactions

When taken over the short term, most of the side effects associated with PPI use are mild and transient. The most common include constipation, diarrhea, flatulence, headache, upset stomach, nausea, and vomiting.

Increasing evidence suggests that long-term use may result in more serious problems. Among them:

  • It has been suggested that PPI use can interfere with the absorption of calcium, leading to bone fractures in certain cases. In response, the U.S. Food and Drug Administration issued warnings in 2011 advising that over-the-counter PPIs should be used for no longer than two weeks at a time for up to three treatments per year.
  • Long-term PPI use has also been associated with a slight increase in the risk of community-acquired pneumonia and Clostridioides difficile infection.
  • A recent study shows a 20% to 50% higher risk of chronic kidney disease in PPI users.
  • A similar study suggested that persons who took PPIs regularly had a 44% greater risk of dementia.

The research findings highlight the fact that PPIs should only be used for short-term relief or treatment rather than as a means to prevent gastric illnesses on a long-term basis.

Many of these adverse effects appear connected to the fact that PPIs not only turn off acid pumps in the stomach but in the rest of the body, as well. This includes the part of a cell called the lysosome which uses acid to clear waste. Without the means to do so, the waste can accumulate and cause the cell to deteriorate and age. This phenomenon may account for the increases seen in the studies.

11 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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  2. Harvard Health Publishing, Harvard Medical School. Do PPIs have long-term side effects?

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  4. Masaoka T, Suzuki H, Hibi T. Gastric epithelial cell modality and proton pump inhibitor. J Clin Biochem Nutr. 2008;42(3):191-6. doi:10.3164/jcbn.2008028

  5. Open Anesthesia. The International Anesthesia Research Society. H2-blockers: onset time.

  6. International Foundation for Gastrointestinal Disorders, Inc. Proton pump inhibitors (PPIs), questions and answers about PPIs.

  7. National Health Services. Omeprazole.

  8. U.S. Food & Drug Administration. FDA drug safety communication: possible increased risk of fractures of the hip, wrist, and spine with the use of proton pump inhibitors.

  9. Lazarus B, Chen Y, Wilson FP, et al. Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med. 2016;176(2):238-46. doi:10.1001/jamainternmed.2015.7193

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Additional Reading

By Sharon Gillson
 Sharon Gillson is a writer living with and covering GERD and other digestive issues.