Proton Pump Inhibitors (PPIs): Uses, Types, Side Effects

Proton pump inhibitors (PPIs) are a group of drugs that reduce the amount of acid in your stomach. PPIs help treat certain acid-related conditions, such as acid reflux and stomach ulcers.

While most PPIs come in oral forms, some are also available as injections. Many PPIs are only available with a prescription from a healthcare provider, but some may be purchased over the counter.

Proton pump inhibitors help decrease stomach acid production. The medications do this by blocking the proton pump channel—a type of protein—in certain cells of the stomach wall. Blocking this channel prevents the production of stomach acid, which reduces acid-related symptoms like heartburn. 

Excessive stomach acid can cause various medical conditions, and PPIs may be used to treat many of them. These conditions can include: 

• Gastroesophageal reflux disease (GERD), which happens when stomach acid repeatedly flows back up into your esophagus 
• Ulcers (sores) in your stomach or duodenum (the first part of the small intestine)
• Ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs)
• Zollinger-Ellison syndrome, when tumors in your pancreas or duodenum cause your stomach to make too much acid 
• Erosive esophagitis, acid-related damage to the lining of the esophagus

Although PPIs are effective treatment options, they take time to work. It can take around three days for PPIs to reach their full effects of suppressing stomach acid. You may start to see improvement in your heartburn symptoms earlier, though.

If you’re taking a PPI for a digestive condition, such as stomach ulcers, it can take several weeks for the drug to fully treat your condition. 

All PPIs work similarly to decrease stomach acid production by blocking the proton pump channel. Some PPIs differ in the conditions they are approved to treat and whether they require a prescription. 

Protonix (Pantoprazole)

Available by prescription only, Protonix is approved to treat erosive esophagitis related to GERD. Healthcare providers may prescribe Protonix for this use in adults and children ages 5 years or older. 

The drug is also approved for conditions marked by overproduction of stomach acid, such as Zollinger-Ellison syndrome. 

Prevacid (Lansoprazole)

Prevacid is available both over the counter (OTC) and with a prescription. The OTC version is approved in adults to treat frequent heartburn, which is defined as heartburn that occurs two or more days per week. 

The prescription version is used to treat GERD, erosive esophagitis, and certain duodenal or gastric (stomach) ulcers, including those caused by NSAID use. Prevacid is approved for GERD and erosive esophagitis in children ages 1 year or older. The medication may also be used to treat conditions relating to excessive stomach acid, such as Zollinger-Ellison syndrome. 

Healthcare providers may prescribe Prevacid with antibiotics for Helicobacter pylori infections, a bacteria that commonly causes stomach ulcers.

Prilosec (Omeprazole)

Prilosec is available OTC and by prescription. OTC Prilosec is approved for frequent heartburn in adults. 

Prescription Prilosec is approved by the United States Food and Drug Administration (FDA) to treat GERD, erosive esophagitis, duodenal and gastric ulcers, and conditions such as Zollinger-Ellison syndrome. It may also be prescribed with antibiotics to treat H. pylori infections. 

Prilosec is similar to Prevacid in that they both have OTC and prescription options. However, to use Prilosec for GERD or erosive esophagitis, you have to be 2 years or older (as opposed to 1 year for Prevacid). 

Nexium (Esomeprazole)

Nexium is also available OTC and with a prescription. The OTC version of esomeprazole may be used for frequent heartburn in adults. 

The prescription version of Nexium is used for similar conditions as other PPIs, including erosive esophagitis, GERD, Zollinger-Ellison syndrome, and H. pylori infections. It can also be prescribed to prevent NSAID-related stomach ulcers. However, in the treatment of GERD and erosive esophagitis, Nexium is only approved for children ages 12 years or older.

Dexilant (Dexlansoprazole)

Dexilant is only available with a prescription from a healthcare provider. It’s FDA-approved to treat erosive esophagitis and GERD in people ages 12 years or older. It may also be prescribed to relieve heartburn and prevent erosive esophagitis from coming back. 

Aciphex (Rabeprazole) 

Aciphex is only available by prescription. It’s approved by the FDA to treat GERD, duodenal ulcers, and conditions such as Zollinger-Ellison syndrome. Similar to other prescription PPIs, Aciphex may also be used with antibiotics to treat H. pylori infections. Healthcare providers may prescribe Aciphex to treat GERD in children ages 12 years or older. 

All proton pump inhibitors are available in oral forms, either as tablets, capsules, or granules. Some PPIs—including lansoprazole, pantoprazole, and esomeprazole—come as injections that are given intravenously (in the veins). Intravenous (IV) forms are used in situations where stomach acid must be blocked right away.

While oral PPIs are highly effective in managing acid-related conditions, there are certain situations when a healthcare provider may prescribe the IV form. For example, IV PPIs may be used when oral medication cannot be taken.

There are certain medical conditions, such as bleeding peptic ulcers, that require a significant reduction in stomach acid. In this situation, high-dose oral PPIs and high-dose IV PPIs are both effective treatment options.

Otherwise, oral and IV proton pump inhibitors work similarly in the body and have comparable effectiveness. Oral PPIs are the more common form because they are easier to administer and more cost-effective. 

In most cases, proton pump inhibitors are prescribed for the short-term treatment of acid-related conditions. When used for a short time, side effects are typically mild and resolve on their own. Mild side effects may include:

• Headache
• Diarrhea
• Constipation
• Nausea
• Itching

Although it’s rare, PPIs may cause serious side effects, especially if they’re taken in the long term. Serious side effects of PPIs include:

• Kidney damage
• Infections
• Low blood levels of certain micronutrients, including vitamin B12, magnesium, and calcium
• Severe skin reactions
• Certain kinds of lupus
• Certain types of stomach polyps (masses of cells found in the stomach lining)

Before starting treatment with a proton pump inhibitor, there are a few things you and your healthcare provider may discuss. 

Drug Interactions

PPIs work by reducing your body’s production of stomach acid. This lowers the acidity level in the stomach, which can change the way certain drugs work in your body. Many drugs require an acidic environment to be absorbed. Without an acidic environment, they may not be absorbed as well. This can make the drug less effective. 

Because all PPIs work similarly, they all can interact with drugs that rely on a high level of acidity in the stomach. These drugs may include:

• Antifungals, such as Nizoral (ketoconazole) or Sporanox (itraconazole)
• Mycophenolate, which prevents transplant organ rejection after a kidney, heart, or liver transplant and is sold under brand names like CellCept and Myhibbin 
• Certain HIV medications, such as Reyataz (atazanavir) and Crixivan (indinavir)

Other drugs that PPIs may interact with include: 

• Trexall (methotrexate)
• Coumadin (warfarin)
• Lanoxin (digoxin)

Some PPIs interact with additional medications. Prilosec and Nexium may interact with Plavix (clopidogrel), Rifadin (rifampin), and St. John’s wort. Prevacid can interact with theophylline, a medication that can help with breathing in asthma and other lung conditions. Theophylline is sold under brand names like Elixophyllin and Theolair.

Depending on the specific interaction, your healthcare provider may have you avoid taking the medications together, separate the doses of your PPI and the interacting drug, or adjust the dose of the interacting medication. 

Other drug interactions may occur. Talk with your healthcare provider about all of the medications you take, including prescriptions, OTC medications, and supplements, before you start taking a PPI.

Use During Pregnancy and Breastfeeding

Research suggests that PPIs are generally safe to use during pregnancy. There doesn’t seem to be an increased risk for pregnancy complications like low birth weight or structural changes at birth. Still, it is a good idea to discuss medication safety with your healthcare provider before starting a medication while pregnant.

Some PPIs, including Prilosec, can pass into breast milk in small amounts. However, the baby’s stomach acid breaks down the medication, so the PPI is not absorbed. That means it’s typically OK to take PPIs while breastfeeding, but you should consult with your healthcare provider to make sure.

Stopping PPI Treatment

When the time comes to stop your PPI, it’s important that you talk to your healthcare provider before making any changes. If you stop taking your PPI abruptly, your symptoms can come back or worsen.

Your healthcare provider may develop a plan for you to lower your dose slowly over time until it’s safe for you to stop the drug entirely. They may also recommend an alternative heartburn medication if you have breakthrough symptoms.

Proton pump inhibitors are typically well-tolerated when taken in the short term. However, if your symptoms continue or worsen, it’s a good idea to reach out to your healthcare provider. 

You should also contact your healthcare provider if you develop side effects that are serious or not going away. These may include:

• Less urine than normal
• Bloody urine
• Severe diarrhea
• Watery stool
• Stomach pain or fever that doesn’t go away
• Joint pain
• Rash on your cheeks or arms
• Seizures
• Irregular heartbeat
• Tremors (shakiness)

Although it’s rare, you can develop serious side effects that require prompt medical care. If you experience any side effects that are severe and feel life-threatening, call 911 or your local emergency number for immediate medical help. Examples may include:

• Difficulty breathing
• Severe rash, including blistering, peeling, or bleeding, accompanied by a fever, chills, body aches, or shortness of breath
• Sudden chest pain

Proton pump inhibitors (PPIs) are drugs used for various acid-related conditions. These conditions include GERD, stomach ulcers, and erosive esophagitis. PPIs work by blocking the proton pump enzyme in certain cells of the stomach, which decreases the production of stomach acid.

While most PPIs are available with a prescription, some can be purchased over the counter (OTC). Prescription PPIs are typically used for different conditions in comparison to OTC versions.

PPIs are usually used for short-term treatment. In most cases, they are well-tolerated. Still, they have a risk of mild to serious side effects, especially if they are taken over a long period. All PPIs can interact with other drugs, so it’s important to discuss your full medication list with your healthcare provider before starting a PPI.