Proton Pump Inhibitors

Proton pump inhibitors (PPIs) are a group of medicines that decrease stomach acid production. They can help relieve symptoms of chronic acid reflux (GERD) and stomach ulcers. PPIs are available both over the counter and by prescription. Brands include Nexium, Prevacid and Prilosec.

Conditions that proton pump inhibitors treat include chronic acid reflux and Zollinger-Ellison syndrome.
Taking a proton pump inhibitor alone or with another medicine (like an antibiotic) can help treat conditions involving excess stomach acid.

What are proton pump inhibitors (PPIs)?

Proton pump inhibitors are a class of drugs that reduce how much acid your stomach makes. Stomach acid serves an important purpose. It breaks down food so you can digest it. Stomach acid also kills harmful germs in your gut that may make you sick.

Too much stomach acid or stomach acid in the wrong place can cause problems, though, like stomach ulcers or acid reflux. PPIs treat these issues and others. You should use them if you have long-term issues related to excess stomach acid.


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What conditions do proton pump inhibitors treat?

Proton pump inhibitors primarily treat conditions that arise when stomach acid irritates or damages parts of your digestive system, like your stomach, duodenum (the part of your small intestine closest to your stomach) or your food tube (esophagus). PPIs are used to treat:

  • GERD (Chronic acid reflux): PPIs relieve symptoms of GERD, like heartburn. With GERD, stomach acid leaks into your esophagus, irritating it. The acid can damage the lining of your esophagus (erosive esophagitis). PPIs reduce stomach acid, allowing your esophagus time to heal and repair.
  • Stomach (peptic) and duodenal ulcers: PPIs can help heal ulcers in your stomach and small intestine that form when stomach acid damages your stomach’s protective inner lining. They can also help heal and prevent ulcers that form as a result of taking NSAIDs (nonsteroidal anti-inflammatory drugs). Up to 30% of people who regularly take NSAIDs develop stomach ulcers.
  • H. pylori infection: PPIs work with antibiotics to kill H. pylori bacteria in your gut. The PPIs lower your stomach’s acidity (pH level) so the antibiotics can kill bacteria more effectively.
  • Zollinger-Ellison syndrome: PPIs counteract the effects of Zollinger-Ellison syndrome. With this rare condition, tumors release a hormone that promotes stomach acid production.

How do proton pump inhibitors work?

Proton pump inhibitors block an enzyme that produces stomach acid. It’s called the hydrogen-potassium ATPase pump, or the “proton pump,” for short. Think of it this way: proton pump inhibitors “inhibit” (or prevent) the proton pump from completing the chemical processes needed to make stomach acid.

PPIs don’t stop the production of all stomach acid. You’ll still have enough to digest food. If you were to take a PPI daily for about five days, the drugs would reduce about 65% of your stomach acid. You’d still have the remaining 35% for your stomach to break down food.


Which drugs are proton pump inhibitors?

PPIs are available over the counter (OTC) or with a prescription (Rx), depending on the brand.

PPIs available OTC and with an Rx

PPIs only available with an Rx

How do you take them?

You take them by mouth, as either a capsule or tablet. With some brands, you can mix the powder inside the capsule with foods like applesauce. This can help if you have trouble swallowing pills.

Read the instructions on the package carefully before you take them so you know how to get the most benefits from taking them. Depending on the brand, you may need to take them on an empty stomach, 30 minutes to an hour before eating. Getting the timing right gives the medicine time to work before your stomach produces acid in response to food.


How much should I take?

Talk to a healthcare provider to determine how strong of a dose you need and how often you need to take PPIs. They can recommend a dose strong enough to help you without putting you at risk of side effects.

Some people only need one pill before breakfast. Others take two pills a day, usually one before breakfast and one before dinner. You may be fine with taking PPIs every other day.

Eventually, you may need to reduce your dosage. A healthcare provider can advise you on this.

How long does it take for PPIs to work?

It may take 24 hours to four days to notice the full benefits of taking PPIs.

If your symptoms are unexpected and need quick relief, try an antacid or a histamine blocker (H2), like Pepcid® or Tagamet®, instead. For example, if you ate a spicy meal and suddenly have heartburn, you may be better off reaching for these options first. They help provide relief within minutes or hours instead of days. But their benefits wear off more quickly than PPIs.

PPIs are considered the better option if you have chronic (long-lasting) issues with stomach acid production.

What are the side effects of using proton pump inhibitors?

Most people who take PPIs don’t experience issues. As with any medication, there are potential side effects, including:

  • Abdominal pain.
  • Constipation.
  • Diarrhea.
  • Dizziness.
  • Dry mouth.
  • Headaches.
  • Fever.
  • Gas.
  • Light-headedness.
  • Itching and rash.
  • Vomiting.

Although PPIs are generally considered safe, researchers have identified potential risks associated with them, especially when using them long-term. PPIs may increase your risk of:

  • A Clostridioides difficile (C. diff) infection. PPIs may change the balance of bacteria in your gut, increasing your risk of an infection.
  • A fracture. PPIs may make it more difficult for your body to absorb enough calcium, a mineral that keeps your bones strong. The FDA warns that PPIs may increase your risk of breaking your hip, wrist or spine.
  • Kidney disease. They may increase your chances of developing chronic kidney disease (CKD) or cause the disease to progress.
  • A nutritional deficiency. PPIs may prevent your small intestine from absorbing enough magnesium or B12. Magnesium helps your muscles and nerves work effectively. Vitamin B12 helps keep your nervous system and red blood cells healthy.

More research is needed to understand the connection between PPIs and potential risks. In the meantime, providers usually recommend you take the PPI dosage in the shortest time frame possible to improve your symptoms without increasing your risk of potential side effects.

When should I contact my healthcare provider?

If you have a PPI prescription, contact your provider with questions about taking them, including when it’s safe to stop or taper your medication.

Contact your healthcare provider if you take over-the-counter PPIs and find you need them daily to control symptoms. They can advise you on how strong a dosage you need and how often you should take them.

You should also contact your provider if you notice concerning side effects, including:

  • An allergic reaction (rash, hives, swelling).
  • Kidney damage (you’re peeing less or have swelling in your hands, ankles or feet).
  • Low magnesium (fatigue, irregular heartbeat, muscle pain).
  • Low vitamin B12 (pain, tingling or numbness in your hands or feet, dizziness or confusion).
  • Skin that’s red, blistering or peeling.
  • Severe diarrhea.
  • Fever.

A note from Cleveland Clinic

Too much stomach acid — or stomach acid in the wrong place — can be painful and damage your digestive system. A variety of medications are available that can help if you’re experiencing symptoms related to excess or out-of-place stomach acid.

For short-term relief, your best met may be an antacid or an H2 blocker. If you have frequent heartburn or a stomach ulcer, your healthcare provider may recommend a PPI instead. They’ve been around for years and are considered safe and effective treatments. Many people rely on them for relief.

Medically Reviewed

Last reviewed on 09/28/2023.

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