Proton pump inhibitors, which include familiar brand name medicines such as Nexium, Prilosec and Prevacid, are among the most prescribed drugs in the United States.

More than 15 million Americans have prescriptions for PPIs, and many millions more buy over-the-counter versions of the drugs, according to research from Washington University in St. Louis.

PPIs account for $10 billion in health care spending in the United States, and global spending on the drugs tops $25 billion per year, according to articles in Pharmacy Today and Therapeutic Advances in Drug Safety.

In May 2018, Dr. Daniel Freedberg, a gastroenterologist for New York-Presbyterian Hospital, wrote in the opinion magazine of the American Gastroenterological Association that up to 15 percent of Americans had used a PPI sometime in the last year and as many as 1 in 10 consumers had taken a PPI within the last month.

PPIs are very effective at treating conditions caused by excess stomach acid. But they are not intended for occasional heartburn.

The U.S. Food and Drug Administration warns people to never take over-the-counter versions for more than 14 days. And the agency cautions against taking a 14-day course more than three times per year.

Studies have found long-term PPI use may result in serious side effects, including bone fractures and sometimes life-threatening kidney problems. Always consult with a doctor before you make changes to your medications. Stopping PPIs without a step-down plan can result in serious health problems.

What Are PPIs and How Do They Work?

PPIs are the most powerful type of medicine available for reducing stomach acid, according to Harvard Health Publishing. The medicine comes in capsules, tablets and/or a powder, depending on the brand. Instructions usually say to take the medicine a half-hour or an hour before the first meal of the day.

Your stomach relies on acid to help you digest the food you eat. Proton pumps in the lining of your stomach produce the acid. But excess acid can damage the esophagus or create a burning sensation in the chest called heartburn.

Once a PPI enters the bloodstream, it blocks the tiny pumps from churning out gastric acid.

Brands and Types

The FDA approved Prilosec as a prescription treatment for gastroesophageal reflux disease, or GERD, in 1989. It was the first PPI approved in the United States.

Since then, several other brand name PPIs have hit the market. The FDA has also approved over-the-counter versions and a lengthy list of generic versions of the drugs.

Prescription & OTC PPIs

Brand Name Generic Name Over-The-Counter Versions Available
Nexium Esomeprazole Nexium 24HR
Prevacid Lansoprazole Prevacid 24HR
Prilosec Omeprazole Prilosec OTC
Zegerid Omeprazole with sodium bicarbonate Zegerid OTC
AcipHex Rabeprazole None
Dexilant Dexlansoprazole None
Protonix Pantoprazole None
Vimovo Esomeprazole and Naproxen None

What Do PPIs Treat?

Prescription and over-the-counter versions of PPIs are approved to treat different conditions. But doctors may tell people who need prescription treatment to use over-the-counter versions to save money.

Prescription PPIs are approved to treat GERD and GERD-related laryngitis; duodenal ulcers and Helicobacter pylori infection associated with them; gastric ulcers; erosive esophagitis; and hypersecretory conditions, such as Zollinger-Ellison syndrome.

Over-the-counter PPIs are approved to treat only frequent heartburn.

Off-Label Uses

Off-label uses are uses that the FDA has not approved. One of the most common off-label uses of PPIs is when patients take the over-the-counter versions of the drugs for longer than the agency recommends.

The FDA has approved over-the-counter PPIs only for a 14-day course of treatment up to three times per year. But the agency acknowledges that consumers on their own or based on a doctor’s recommendation may break those rules. The FDA considers this an unapproved use of PPIs.

“Be aware that consumers either on their own, or based on a health care professional’s recommendation, may take OTC PPIs for periods of time that exceed the directions on the OTC label. This is considered an off-label (unapproved) use,” the FDA said in a March 2011 safety announcement.

Be aware that consumers either on their own, or based on a health care professional's recommendation, may take OTC PPIs for periods of time that exceed the directions on the OTC label. This is considered an off-label (unapproved) use.

Taking OTC PPIs for longer than the FDA-approved regimen can have serious consequences. Studies have found long-term use can result in kidney damage or life-threatening conditions and premature death.

Side Effects

Side effects with PPIs are relatively rare, and the most common side effects tend to be minor. Some of the most common PPI side effects include:

  • Abdominal pain
  • Anxiety
  • Constipation
  • Diarrhea
  • Dizziness
  • Drowsiness
  • Dry mouth
  • Gas
  • Headaches
  • Inability to properly absorb nutrients
  • Joint pain
  • Rash or other skin issues

But these drugs can also cause serious side effects in very rare cases. Some of these can result in serious injury, long-term health problems and life-threatening conditions. People have filed lawsuits against PPI manufacturers to seek compensation for pain and suffering and to cover medical expenses.

The most serious PPI side effects and risks revealed in studies include:

  • Bacterial infections
  • Bone fractures
  • Heart attack or heart failure
  • Kidney disease or injuries
  • Premature death
  • Damage to arteries
  • Depression
  • Stroke

Most serious side effects are associated with long-term use of PPIs. The FDA has stated on multiple occasions that the risk of serious health problems increases with longer durations of PPI use. The agency also advises careful use of PPIs.

Proton Pump heart attack side effects

Overuse and Misuse

A study published in Therapeutic Advances in Drug Safety in November 2018 estimated that between 25 percent and 70 percent of PPI prescriptions are for a condition the drugs do not treat.

PPIs are more expensive than antacids, such as Rolaids or Tums, and H2 blockers, such as Pepcid, Zantac or Tagamet. And those alternatives may be better suited for you if you experience only occasional heartburn.

In most cases, PPIs should only be taken for a short time. Most evidence suggests prescription versions shouldn’t be taken for more than a year except in some specific cases, according to a study published in Annals of Family Medicine in 2018. But the study found 45 percent of patients who had been prescribed the drugs were still taking them after 15 months.

One of the most notable forms of overprescribing PPIs happens when a person is hospitalized. The drugs are often given to hospitalized patients to prevent heartburn during their stay. But in many cases, doctors will continue to prescribe the drugs for months or years even though the patients don’t need them.

The problem with PPIs is not that they are dangerous but that they are overprescribed.

Doctors may prescribe or recommend OTC proton pump inhibitors if a patient has a few bouts with reflux. But the patient may wind up taking the drugs for months or years.

It is a good idea to at least once a year have your doctor or pharmacist review all the drugs you are taking. They can determine whether you should still be on drugs like PPIs.

In his 2018 article in AGA Perspectives, Freedberg argued that PPI benefits outweigh the risks if they are used appropriately, but he also pointed out that PPI prescriptions are often given to patients for an inappropriate condition or continued for too long after they’re first prescribed.

He said serious side effects from long-term use are extremely rare. But in a warning to his fellow gastroenterologists, he wrote that if one of their patients suffers an adverse event from unnecessarily taking PPIs, “you will regret it.”

“The problem with PPIs is not that they are dangerous but that they are overprescribed,” Freedberg said.

Stopping PPIs Safely

You should never stop taking a PPI without first talking to a doctor, pharmacist or other health care professional who has a clear understanding of the drug’s effects. Stopping PPI use suddenly can cause the underlying condition to come back worse than before. It may also lead to other health problems.

In some cases, it may be safer to continue taking the PPI than to stop taking it. If a doctor believes you could benefit from switching to a different treatment, he or she will likely work out a way to get you off the drug gradually.

Last Modified: September 10, 2019

25 Cited Research Articles

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