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Two of the most commonly prescribed proton pump inhibitors (PPIs) are omeprazole (Prilosec) and esomeprazole (Nexium). Both are now available as over-the-counter (OTC) drugs.

Heartburn is difficult enough. Making sense of your medication choices for gastroesophageal reflux disease (GERD) can make it even more challenging.

Let’s compare Prilosec and Nexium to see what benefits one medication may offer over the other.

Proton pumps are enzymes found in the parietal cells of your stomach. They make hydrochloric acid, the main ingredient of stomach acid.

Your body needs stomach acid for digestion. However, when the muscle between your stomach and esophagus doesn’t close properly, this acid can end up in your esophagus. This causes the burning feeling in your chest and throat that’s associated with GERD.

Stomach acid in your esophagus can also cause:

PPIs decrease the amount of acid that’s made by proton pumps. PPIs work best when you take them 30 minutes to an hour before a meal. You’ll need to take them for several days before they’re fully effective.

PPIs have been in use since 1981. They’re considered the most effective medication for reducing stomach acid.

PPIs like Nexium and Prilosec are used to treat gastric acid-related conditions, including:

Omeprazole (Prilosec) and esomeprazole (Nexium) are similar drugs. However, there are minor differences in their chemical makeup.

Prilosec contains two isomers of the drug omeprazole, while Nexium only contains one isomer.

Isomer is a term for a molecule that includes the same chemicals but is arranged in a different way. So, you could say that omeprazole and esomeprazole are made of the same building blocks but are put together differently.

While the differences in isomers might seem minor, they can result in differences in how drugs work.

For example, the isomer that’s in Nexium is processed more slowly in your body than Prilosec. This means that there are higher levels of the drug in your bloodstream, and esomeprazole may decrease acid production for a longer period of time.

It may also work slightly faster to treat your symptoms compared with omeprazole. Esomeprazole is also broken down differently by your liver, so it may lead to fewer drug interactions than omeprazole.


Some studies indicate that the differences between omeprazole and esomeprazole may offer some advantages to people with certain conditions.

An older study from 2002 found that esomeprazole provided more effective control of GERD than omeprazole at the same dosages.

However, in a 2007 article in American Family Physician, doctors questioned these and other studies on PPIs. They cited concerns such as:

  • differences in the amount of active ingredients given in the studies
  • the size of the studies
  • the clinical methods used to measure effectiveness

The authors analyzed 41 studies on the effectiveness of PPIs. They found that there’s little difference in the effectiveness of PPIs.

So, while there’s some data to suggest that esomeprazole is more effective at relieving symptoms, most experts agree that the PPIs have similar effects overall.

The price of relief

The biggest difference between Prilosec and Nexium was price when reviewed.

Until March 2014, Nexium was available only by prescription and at a significantly higher price. Nexium now offers an over-the-counter (OTC) product that’s priced competitively with Prilosec OTC. However, generic omeprazole may be less expensive than Prilosec OTC.

Traditionally, insurance companies didn’t cover OTC products. However, the PPI market has led many to revise their coverage of Prilosec OTC and Nexium OTC. If your insurance still doesn’t cover OTC PPIs, a prescription for generic omeprazole or esomeprazole may be your best option.

“Me too” drug?

Nexium is sometimes called a “me too” drug because it’s so similar to Prilosec, an existing drug. Some people think that “me too” drugs are just a way for drug companies to make money by copying drugs that are already available. But others have argued that “me too” drugs can actually decrease drugs costs, because they encourage competition between the drug companies.

Work with your doctor or pharmacist to decide which PPI is best for you. In addition to cost, consider things like:

  • side effects of the medication
  • other medical conditions you have
  • other medications you’re taking

Most people don’t have side effects from PPIs. Infrequently, people may experience:

  • diarrhea
  • nausea
  • vomiting
  • headache

These side effects may be more likely with esomeprazole than omeprazole.

It’s also believed that both of these PPIs may increase the risk of:

  • spine and wrist fractures in postmenopausal people, especially if the medications are taken for a year or more or at higher doses
  • bacterial inflammation of the colon, especially after hospitalization
  • pneumonia
  • nutritional deficiencies, including vitamin B12 and magnesium deficiencies

A link to possible dementia risk was reported in a 2016 data analysis, but a larger confirmatory study in 2020 determined that there was no increased risk of dementia from using PPIs.

Many people experience excess acid production when they stop using PPIs. However, why this happens isn’t completely understood.

For most stomach acid issues, it’s recommended that you take PPIs for no longer than 4 to 8 weeks, unless your doctor determines a longer duration of therapy is needed.

At the end of the recommended treatment duration, you should taper off of the medication gradually. Work with your doctor to do so.

Before taking either medication, talk with your doctor to learn about the risk factors and drug interactions associated with the medication.

Risk factors

Certain risk factors may affect how your body tolerates PPIs, including:

  • being of Asian descent, as your body may take longer to process PPIs, and you may need a different dosage
  • having liver disease
  • having had low magnesium levels
  • being pregnant or planning to become pregnant
  • breastfeeding

Drug interactions

Always tell your doctor about all the drugs, herbs, and vitamins you take. Prilosec and Nexium can interact with other medications you might be taking.

The Food and Drug Administration (FDA) has issued a warning that the drug in Prilosec reduces the effectiveness of the blood thinner clopidogrel (Plavix).

You shouldn’t take the two drugs together. Other PPIs aren’t included in the warning because they haven’t been tested for this action.

These drugs should not be taken with either Nexium or Prilosec:

Other drugs can interact with Nexium or Prilosec but may still be taken with either drug. Tell your doctor if you take any of these drugs so they can evaluate your risk:

Generally, you can choose the PPI that’s readily available and costs less. But keep in mind that PPIs treat only the symptoms of GERD and other disorders. They don’t treat the cause and are only indicated for short-term use unless your doctor determines otherwise.

Lifestyle changes should be your first step in controlling GERD and heartburn. You may want to try:

Over time, long-term GERD can lead to esophageal cancer. Although few people with GERD get esophageal cancer, it’s important to be aware of the risk.

PPIs take effect gradually, so they may not be the answer for occasional heartburn or reflux.

Alternatives can offer relief for occasional use, such as:

  • chewable calcium carbonate tablets
  • liquids like aluminum hydroxide and magnesium hydroxide (Maalox) or aluminum/magnesium/simethicone (Mylanta)
  • acid-reducing drugs like famotidine (Pepcid) or cimetidine (Tagamet)

All of these are available as OTC drugs.