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Proton pump inhibitors

Medically reviewed by Carmen Pope, BPharm. Last updated on April 17, 2023.

Other names: PPIs

What are Proton Pump Inhibitors (PPIs)?

Proton pump inhibitors (PPIs) reduce the production of acid by the stomach. They work by irreversibly blocking an enzyme called H+/K+ ATPase which controls acid production. This enzyme is also known as the proton pump and is found in the parietal cells of the stomach wall.

What are Proton Pump Inhibitors (PPIs) used for?

PPIs treat conditions that are caused by either an overproduction of stomach acid or exacerbated by stomach acid. Taking a PPI once a day inhibits around 70% of the proton pumps, so a small amount of acid is still available for food digestion.

PPIs may be used for the treatment of:

What are the differences between Proton Pump Inhibitors?

All PPIs work in the same way, by inhibiting the proton pump. However, there are differences in their likelihood of drug interactions, and in the way they bind to the proton pump. This can affect how long they last for.

All the PPIs available in the U.S. are metabolized in the liver by certain liver enzymes (mainly CYP2C19 and 3A4). There is a lot of individual variation in the way these liver enzymes work, and experts have identified three categories of people; extensive metabolizers (homEM), poor metabolizers (PM), and people that sit somewhere in between (hetM).

Approximately 3% of Caucasians and 15-20% of Asians are PM. PM take longer to excrete the drug and therefore their response to PPIs is increased several fold. For example, the pH of gastric acid is around 6 in PM after PPIs compared to around 3-4 in extensive metabolizers (where 1 is the most acidic pH). Metabolism is also affected in people of an older age and in those with liver disease. Esomeprazole is the only PPI that is well tolerated by people with liver disease. The extent that somebody is able to metabolize a PPI can also affect their risk of drug interactions. 

Generic name Brand name examples
dexlansoprazole Dexilant
esomeprazole Nexium
lansoprazole Prevacid
omeprazole Prilosec
pantoprazole Protonix
rabeprazole Aciphex

Are Proton Pump Inhibitors safe?

When taken at the recommended dosage for the recommended duration of time, PPIs are considered safe. However, they have been associated with several serious adverse effects including:

  • Acute interstitial nephritis (a type of kidney failure): May occur at any point during PPI treatment
  • Clostridium difficile-associated diarrhea: This is a particularly severe and persistent type of diarrhea
  • An increased risk for osteoporosis-related fractures of the hip, wrist, or spine: The risk is higher in people who received high-dose therapy (typically multiple daily doses), and with PPI treatment that lasts longer than one year
  • Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE)
  • An inhibition of the effect of clopidogrel, a medicine used to reduce the ability of platelets to clot in people with heart disease.

In addition, there is a risk that the use of PPIs may mask the symptoms of gastric cancer. All patients with a suboptimal response to PPIs or whose symptoms recur following PPI withdrawal should have additional diagnostic testing, and an endoscopy should be considered in older people before treatment initiation.

Patients should only take PPIs as directed by their doctor or according to the instructions on the packet if bought over the counter.

What are the side effects of Proton Pump Inhibitors?

PPIs are generally well tolerated. The more common side effects reported with their use include:

For a complete list of side effects, please refer to the individual drug monographs.

List of Proton pump inhibitors

View by  Brand | Generic
Drug Name Avg. Rating Reviews
omeprazole / sodium bicarbonate systemic (Pro)
8.3
39 reviews
rabeprazole systemic (Pro)
8.2
84 reviews
dexlansoprazole systemic (Pro)
6.7
249 reviews
lansoprazole systemic (Pro)
6.6
142 reviews
esomeprazole systemic (Pro)
5.9
266 reviews
pantoprazole systemic (Pro)
5.0
426 reviews
omeprazole systemic (Pro)
4.6
491 reviews
vonoprazan systemic
No reviews
For ratings, users were asked how effective they found the medicine while considering positive/adverse effects and ease of use (1 = not effective, 10 = most effective).

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.