What Is a Proton Pump Inhibitor (PPI)?

What are PPI drugs?

PPI - Proton Pump InhibitorStomach acids are necessary for the proper digestion of our foods. But stomach acid can erode the body when not contained in its proper place. The stomach has a protective mucous barrier that protects its lining. When this mucous barrier is compromised, stomach acid can eat away at the stomach causing ulcers. If stomach acid refluxes into the esophagus, irritation occurs. The esophagus doesn’t have a mucous barrier to withstand acid like the stomach. This irritation is the cause of heartburn. If left untreated, erosion of the esophagus may occur.

A proton pump inhibitor (PPI) is a drug used to reduce the production of stomach acid giving the esophagus, stomach, and duodenum (first part of the intestines) time to heal from irritation and erosive damage. The decrease in acid production will also help reduce acid reflux related heartburn.

PPIs are the strongest inhibitors of acid available but are not used for immediate relief of heartburn. It may take days before a PPI will start providing relief from acid irritation. Relief will vary depending on the reason for taking the drug and the rate at which the body heals. If taking to treat an ulcer, relief may take longer.

PPIs are available in prescription and over the counter (OTC) versions. They include:

  • AcipHex (rabeprazole)
  • Dexilant (dexlansoprazole)
  • Kapidex (dexlansoprazole)
  • Losec (omeprazole)
  • Nexium (esomeprazole)
  • Prevacid (lansoprazole)
  • Prilosec (omeprazole)
  • Protonix (pantoprazole)
  • Rapinex (omeprazole)
  • Vimovo (esomeprazole, magnesium, and naproxen)
  • Zegerid (omeprazole and sodium bicarbonate)


What can be treated with PPI therapy?

PPIs are typically used: 1

  • To treat damage to the lower esophagus caused by acid reflux and gastroesophageal reflux disease (GERD).
  • To relieve GERD symptoms and prevent further complications of GERD.
  • To treat erosive esophagitis.
  • For maintenance to prevent esophagitis from recurring after the esophagus has healed.
  • To treat Barrett’s esophagus.
  • To treat esophageal, gastric, and duodenal ulcers by reducing acid allowing ulcers to heal.
  • In combination with antibiotics for eliminating Helicobacter pylori, which can contribute to the formation of esophageal, gastric, and duodenal ulcers.
  • For excessive gastrointestinal acid secretory disorders.


Taking a PPI

PPIs are taken by mouth as tablets or capsules with a glass of water before the first meal of the day. It is important to drink the water along with the pill. Not drinking enough water can prevent it from working properly.

Talk with your doctor to know if you should take a PPI and for how long. Though available in OTC form, PPIs should not be taken without direction from your doctor. Your doctor may prescribe you a PPI for different time intervals depending on your health issue. The packaging on OTC PPIs clearly states to take it for no longer than 14 days or more often than every 4 months unless directed by a doctor. This is to prevent negative side effects that can occur when using the medication long term.


What are the PPI side effects and precautions?

PPIs are for temporary use and not intended for long-term daily use. When taken properly, they can be an effective treatment option. Long-term use, however, may lead to serious complications.

Please see the warnings that come with your particular PPI for a full list of possible side effects and precautions.

Common side effects found in temporary use are:

  • Headache
  • Constipation
  • Diarrhea
  • Abdominal pain
  • Flatulence
  • Nausea
  • Itching/rash
  • Vomiting

Precautions when taking a PPI:

Tell your doctor or pharmacist if you are taking other medicines. PPIs can cause serious drug interaction issues. PPIs also reduce stomach acid needed to break down certain medications, thus affecting their absorption.

PPIs may not be advised if you are taking:

  • Certain anti-seizure medicines such as phenytoin
  • Blood thinners such as warfarin, clopidogrel, or cilostazol
  • Prescription antifungal or anti-yeast medicines
  • Diazepam (anxiety medicine)
  • Digoxin (heart medicine)
  • Tacrolimus (immune system medicine)
  • Prescription antiretrovirals (medicines for HIV infection)

Specific precautions for women:

  • If you are breastfeeding, pregnant, or may become pregnant, talk to your health care provider before taking these medicines. They expose the baby to some level of risk, though it is considered minimal. 2

Precautions when using long term:

  • Long-term use may lead to a 16 to 20 percent increase risk of heart attack depending on which PPI you are taking. 3
  • There is an increased risk of chronic kidney disease.
  • There is an increased risk of pneumonia.
  • Stomach acid is beneficial in killing harmful bacteria introduced to the body through foods.
  • There is increased risk of having an Clostridium difficile infection, a bacteria that causes persistent diarrhea. 4
  • Inefficient digestion leads to decreased absorption of vitamin B12, calcium, magnesium, iron and other nutrients.
    • Decreased calcium absorption may lead to bone fractures in the hip, wrist, and spine. 5 This is especially true in those who have osteoporosis.
    • Decreased magnesium absorption can lead to hypomagnesaemia and cardiac arrhythmias. 6
  • Higher levels of acids are useful in closing the lower esophageal sphincter (LES). When the LES is tightening properly, it prevents acid from refluxing into the esophagus.
  • Increased risk of Barrett’s esophagus. 7
  • Getting off PPIs after long-term use can cause a painful rebound in acid. Weaning off PPIs is advisable.



  1. US National Library of Medicine National Institutes of Health “Pharmacology of Proton Pump Inhibitors”.
  2. US National Library of Medicine National Institutes of Health “Are proton pump inhibitors safe during pregnancy and lactation? Evidence to date.
  3. PLOS|ONE “Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population
  4. U.S. Food and Drug Administration “FDA Drug Safety Communication: Clostridium difficile-associated diarrhea can be associated with stomach acid drugs known as proton pump inhibitors (PPIs)
  5. U.S. Food and Drug Administration “FDA Drug Safety Communication: Possible increased risk of fractures of the hip, wrist, and spine with the use of proton pump inhibitors
  6. U.S. Food and Drug Administration “FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of Proton Pump Inhibitor drugs (PPIs)
  7. US National Library of Medicine National Institutes of Health “Proton Pump Inhibitors: The Culprit for Barrett’s Esophagus?



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