Are Proton Pump Inhibitors Dangerous?

Proton pump inhibitors (PPIs) are prescription medications that help with symptoms of acid reflux or heartburn. Appropriate use of PPIs is generally safe. However, some studies have associated certain health risks with long-term use.

How Do Proton Pump Inhibitors Work?

Proton pump inhibitors work by reducing acid secretion in the stomach. The use of PPIs has been increasing since they entered the market in the late 1980s due to their treatment success. Their use has increased from 4% to 8% between 1999 to 2012 in the US adult population. Alarmingly, more than half of this population use them for incorrect medical conditions.^[1] It’s important to work with your doctor to make sure you’re taking the right medications for the right conditions.

Common proton pump inhibitors include:

• Omeprazole (Prilosec)
• Aspirin-Omeprazole (Yosprala)
• Lansoprazole (Prevacid)
• Dexlansoprazole (Dexilent)
• Rabeprazole Sodium (Aciphex)
• Pantoprazole Sodium (Protonix)
• Esomeprazole Magnesium (Nexium)

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Do Proton Pump Inhibitors Increase the Risk of Death?

A study published in 2017 found a small association between the use of PPIs and increased risk of death. The study compared the rate of death among people who took PPIs, histamine 2 receptor antagonists (H2RAs – another type of stomach acid suppressant) or neither medication. 

There was a higher number of deaths reported among people taking PPIs compared to people taking H2RAs or neither medication. However, this study shows only an association and does not prove taking PPIs directly causes death. Due to the nature of the study, the increased risk of death may be real or may be due to chance.^[1,2]

Is It Safe to Take Proton Pump Inhibitors Long-term?

Some studies have associated long-term use of PPIs with a small risk of bone fractures, diarrhea, infection of the gut or lungs, and heart and kidney problems. However, there are no claims that suggest PPIs are the direct cause of these adverse drug outcomes. ^[1,4]

Another study assessing the overall safety of long-term PPI use was published in May 2019. The study reported no adverse drug outcomes except for increased number of gut infections among participants taking a PPI for 3 years compared to participants taking no PPIs.^[3]

Side Effects of Proton Pump Inhibitors

Short-term side effects of proton pump inhibitors are generally mild and may include:

• Headache
• Upset Stomach
• Nausea 
• Vomiting
• Diarrhea
• Constipation
• Flatulence

Let your doctor know of any side effects you experience while taking a PPI.

Should I Stop Taking a PPI?

If you are taking a PPI, you should continue using it as directed by your doctor. PPIs are generally considered safe when taken as directed by your doctor or pharmacist for short periods of time. 

Sometimes, PPIs are used for gastrointestinal diseases that require a long-term or life-long treatment. In such patients, the benefit of PPI use outweighs the small or modest increased risk of adverse drug outcomes. If you are concerned about your PPI use, talk to your doctor or pharmacist about treatment options. ^[4]

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References: 

1.     Xie Y, Bowe B, Li T, et al. Risk of death among users of Proton Pump Inhibitors: a longitudinal observational cohort study of United States veterans. BMJ Open 2017;7:e015735.

2.     Does taking proton pump inhibitors increase the risk of death? Retrieved from: https://www.nps.org.au/professionals/ppis/does-taking-proton-pump-inhibitors-increase-the-risk-of-death. Accessed on 8/12/2019 

3.     Moayyedi P, Eikelboom JW, Bosch Jackie, et al. Safety of proton pump inhibitors based on a large, multi-year, randomized trial of patients receiving rivaroxaban or aspirin. Gastroenterology. 2019 May 29. Pii:S0016-5085(19)40974-8

4.     Wolfe MM. Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders. In: Feldman M & Grover S (Editors). UpToDate. [Internet]. Published place unknown: UpToDate; 2019 [cited Nov 29, 2017]. Available from: https://www-uptodate-com. Accessed on 9/10/2019