• Brian Dooreck, MD

Safety of Proton Pump Inhibitors (PPIs)

Updated: Oct 4, 2020

What is the latest of proton pump inhibitors (PPIs) and long term safety?

A recent, large placebo-controlled trial of 17,598 participants confirmed the safety of proton pump inhibitors (PPIs).

"Researchers find no evidence to support claims that proton pump inhibitors (PPIs) cause serious health issues such as pneumonia, chronic kidney disease, diabetes, and dementia."

Pantoprazole was not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections.

Thus, limiting prescriptions of PPI therapy because of concerns of long-term harm is not appropriate based on this study. However, this risk was lower than estimated by previous systematic reviews of observational studies.

Do Proton pump inhibitors (PPIs) cause serious health issues such as pneumonia, chronic kidney disease, diabetes, and dementia?

Researchers find no evidence to support claims that proton pump inhibitors (PPIs) cause serious health issues such as pneumonia, chronic kidney disease, diabetes, and dementia. This research is published in Gastroenterology, the official journal of the American Gastroenterological Association.

What are Proton pump inhibitors (PPIs)?

PPIs, such as omeprazole, Prilosec, and Nexium are medications that are effective in blocking gastric acid secretion.

PPIs are one of the most widely used drugs in the United States.

"Around 25% of the population has gastroesophageal reflux disease (GERD)"

What are Proton pump inhibitors (PPIs) used for?

PPIs are used for the treatment of peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD), and much rarer conditions such as Zollinger-Ellison syndrome (ZES).

GERD occurs in over 25 percent of the population.

PPIs are also effective in the prevention of NSAID or nonsteroidal anti-inflammatory drug-associated gastroduodenal mucosal injury. NSAIDs are drugs such as ibuprofen and Advil.

PPIs plus antibiotics are used in the treatment of Helicobacter pylori infection.

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Are there drug interactions with Proton pump inhibitors (PPIs)?

Clinically important drug interactions with PPIs are rare and should be addressed with your doctor and pharmacist.

When should I take Proton pump inhibitors (PPIs)?

Ideally, oral PPIs should be administered 30 to 60 minutes before breakfast, or the first meal of the day. This provides for maximal acid suppression.

PPIs should not be administered at the same time with H2-receptor antagonists, such as Pepcid or Ranitidine if also being used.

For how long should I take Proton pump inhibitors (PPIs)?

PPIs should be prescribed at the lowest dose.

Like any medication, use for the shortest duration appropriate.

These drugs are well tolerated in the short term.

Long-term treatment was associated with adverse events in observational studies.

As with all drugs, PPI therapy should only be used when the benefits outweigh the risks. As with all drugs, PPI therapy should be used according to the recommended dose and duration of treatment.

What has been published about PPIs and associated side effects?

  • PPI use has been associated with an increased risk of Clostridium difficile infection. C. difficile infection with diarrhea may occur even in the absence of antibiotic use.

  • PPI use can lead to other enteric infections and microscopic colitis.

  • PPIs can cause hypomagnesemia due to reduced intestinal absorption.

  • Disrupting the stomach's delicate balance may cause changes in the immune system and trigger new allergies.

  • Long-term therapy with PPIs has been associated with vitamin B12 malabsorption.

  • Although an association between PPIs and bone fracture is plausible, direct causality has not been established.

  • PPIs can cause acute interstitial nephritis and chronic kidney disease (CKD), however further studies are needed.

  • The association between PPI use and dementia and pneumonia is not established and is conflicting. The same with an increased risk of death. Most likely is that these associations are due to the overall state of health of the patients, not the use of PPIs, and more studies are needed.

Take away tips if you are on PPIs

  1. Talk to your doctor before making any changes. You have been prescribed PPIs for a reason. Probably to treat a diagnosed medical condition.

  2. Focus on lifestyle modifications for GERD. You may not need long-term use of PPIs or can reduce the dose. Read Heartburn, GERD, Acid Reflux—Are They Dangerous?

  3. Headlines on PPIs can be "scary" and hyped, but if PPIs are needed, and are treating a medical diagnosis, you should stay on them. Especially if the benefits outweigh risks.


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"Balance. Portion control. Keep nutrition simple. Eat Smart. Eat Healthy. 🌱 🌾 🌿"

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