Esomeprazole (Nexium) vs. Omeprazole (Prilosec): 7 Things to Know When Comparing These PPIs

Heartburn. Acid reflux. Gastroesophageal reflux disease (GERD). These digestive conditions are uncomfortable. And many people turn to proton pump inhibitors (PPIs) to help manage them.

Esomeprazole (Nexium, Nexium 24HR) and omeprazole (Prilosec, Prilosec OTC) are two PPIs that treat GERD. Though their names are similar, esomeprazole and omeprazole are not the same. Both medications work well for GERD, but is one preferred over the other? Below, we cover seven things to keep in mind when comparing esomeprazole versus omeprazole.

1. Esomeprazole and omeprazole have different dosage forms available

Both esomeprazole and omeprazole are available over the counter (OTC), as well as with a prescription. But they have slightly different dosage forms available.

All esomeprazole and omeprazole formulations are delayed-release products. This means that the medication is released in the intestines, not the stomach. This prevents the stomach from breaking the medication down before it can have the desired effect.

The table below shows the different OTC and prescription dosage forms that are available for esomeprazole and omeprazole.

*Granule packets are mixed with water at home to make a suspension (liquid) that you drink.

2. Esomeprazole and omeprazole work the same but have different active ingredients

Esomeprazole and omeprazole aren’t the same medication. But they work the same way.

EXPERT PICKS: WHAT TO READ NEXT

• When does omeprazole (Prilosec) start working? Find out how long it takes omeprazole to work and when you may start feeling relief.

• Can probiotics help gastroesophageal reflux disease (GERD)? Learn what the research says about taking probiotics for GERD and heartburn.

• Rapid reflux relief. Learn which home remedies and over-the-counter medications provide quick heartburn relief and when to seek medical care for symptoms that don’t go away.

PPIs block an enzyme (protein) that helps the stomach make acid. This enzyme is called the “proton pump.” By blocking the proton pump, PPIs prevent the stomach from making too much acid. This is helpful because symptoms of GERD (such as heartburn) are a result of excess acid in the stomach.

Chemically, omeprazole and esomeprazole are very similar. In fact, esomeprazole is derived from omeprazole.

Think of omeprazole like the wishbone of a turkey. Omeprazole is like looking at the wishbone as a whole. But if you break the wishbone in half, you get two separate chemicals: R-omeprazole and S-omeprazole (esomeprazole).

Read more like this

Explore these related articles, suggested for readers like you.

Omeprazole or Pantoprazole? Understanding the Differences

Is Omeprazole an Antacid? Pharmacists Answer 13 FAQs About This Common PPI

What to Know About 6 Popular Proton Pump Inhibitors

What You Need to Know About Esomeprazole

View more

Your liver breaks down each chemical a bit differently. And this causes your body to absorb greater amounts of esomeprazole than R-omeprazole. But if you’re only taking esomeprazole, your body only has one chemical to focus on. This distinction may be why esomeprazole lowers stomach acid levels more than omeprazole (more on this later).

3. Esomeprazole and omeprazole have slightly different FDA-approved uses

For the most part, esomeprazole and omeprazole treat the same symptoms and conditions. But there are slight differences.

OTC versions of esomeprazole and omeprazole are FDA-approved for frequent heartburn in adults. Anyone can buy them without a prescription. But you shouldn’t take either of them for longer than 2 weeks unless a healthcare professional tells you otherwise.

Prescription esomeprazole is FDA-approved to:

• Treat GERD

• Treat erosive esophagitis (inflammation of the esophagus)

• Maintain the healing of erosive esophagitis

• Lower the risk of ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin)

• Treat Helicobacter pylori (H. pylori) infections

• Treat Zollinger-Ellison syndrome and other conditions caused by excess acid production

Prescription omeprazole is approved to:

• Treat GERD

• Treat erosive esophagitis

• Maintain the healing of erosive esophagitis

• Treat stomach or intestinal ulcers

• Treat H. pylori infections

• Treat Zollinger-Ellison syndrome and other conditions caused by excess acid production

4. The ways you take esomeprazole and omeprazole are slightly different

It’s best to take esomeprazole or omeprazole on an empty stomach. But while you can take omeprazole 30 to 60 minutes before a meal, you should take esomeprazole at least 1 hour before eating. Taking either medication with food or too soon before eating can cause it not to work as well.

Specific dosages for esomeprazole and omeprazole vary based on the condition you’re treating and your response. Children’s dosages also depend on their age and body weight. Most people take esomeprazole or omeprazole once a day. But there are times your prescriber may recommend taking it twice a day.

Follow the directions on the OTC label or your healthcare professional’s guidance when taking esomeprazole or omeprazole.

5. Both are effective for GERD, but esomeprazole may work a little better for some people

Esomeprazole and omeprazole are both effective for treating GERD and erosive esophagitis. Most people experience similar symptom relief with either PPI. That’s why experts don’t recommend one over the other.

But there are some studies that suggest esomeprazole may work a little better than omeprazole:

• An analysis of 15 studies found that esomeprazole was slightly more effective than omeprazole at healing erosive esophagitis after 8 weeks. But the researchers noted that these results likely wouldn’t make a significant difference for many people.

• An analysis of four studies found that esomeprazole lowered stomach acid levels more than four other PPIs, including omeprazole, in people with GERD. But this study didn’t compare the levels of GERD symptom relief that people experienced.

Despite these studies, experts don’t consider one PPI to be better than the others. But everyone responds to these medications differently. So you may find that one works better for you than the other.

If you don’t feel any symptom improvement after taking a PPI for 2 weeks, let your healthcare professional know. They can let you know if you should switch or adjust your medications.

6. Esomeprazole and omeprazole have similar side effects

Esomeprazole and omeprazole have similar side effects. These are generally mild, especially if you’re only taking the medication short term. More serious side effects are rare and usually only happen if you take the medication long term.

Common side effects

The most common side effects of esomeprazole and omeprazole include:

• Headache

• Diarrhea

• Nausea

• Vomiting

• Gas

• Stomach pain

• Constipation

Serious side effects

Taking esomeprazole or omeprazole for a long time may cause more serious side effects. Possible risks include:

• Severe diarrhea caused by the bacteria Clostridioides difficile

• Low vitamin B12 and magnesium levels

• Kidney damage

• New or worsening lupus

• Weakening of bones

• A higher risk of lung infections, such as pneumonia

• Serious skin reactions

7. Omeprazole interacts with slightly more medications than esomeprazole

In general, esomeprazole and omeprazole interact with the same medications. But omeprazole has slightly more interactions. This can be a reason a healthcare professional may recommend esomeprazole.

For instance, omeprazole interacts with diazepam (Valium) and phenytoin (Dilantin). It can raise the risk of side effects of these other medications. Esomeprazole isn’t known to cause significant problems with either of these medications.

Examples of medications that interact with both esomeprazole and omeprazole include:

• Warfarin (Coumadin, Jantoven)

• Clopidogrel (Plavix)

• Methotrexate (Trexall)

• Digoxin (Lanoxin)

• Citalopram (Celexa)

• St. John’s wort

• Iron supplements

This isn’t a complete list of interactions. Make sure to share your medication list with your healthcare team. This can help them discover and manage potential interactions.

What are some alternatives to omeprazole and esomeprazole?

There are a few available alternatives to omeprazole and esomeprazole:

• For occasional heartburn, OTC antacids such as Tums (calcium carbonate) offer quick relief. But they don’t help prevent symptoms.

• An OTC histamine-2 (H2) blocker, such as famotidine (Pepcid AC), can also be taken as needed for rapid acid reflux relief. It can also be taken daily to help prevent symptoms.

• Voquezna (vonoprazan) is a potassium-competitive acid blocker that treats GERD, erosive esophagitis, and H. pylori infections. It’s a prescription-only medication that works faster and lasts longer than PPIs.

How to save on esomeprazole and omeprazole

Esomeprazole and omeprazole are available as both brand-name medications and lower-cost generics. GoodRx can help you navigate ways to save on your prescription.

• Save with GoodRx. GoodRx can help you save over 95% off the average retail price of the generic versions of esomeprazole and omeprazole. Generic esomeprazole’s price at certain pharmacies is as low as $7.33 with a free GoodRx discount. Generic omeprazole’s price at certain pharmacies is as low as $5.88 with a free GoodRx discount.

• Save with a copay savings card. If you have commercial insurance and meet eligibility requirements, brand-name Nexium’s price is as little as $15 if you use the manufacturer’s savings card.

• Save with a coupon from the manufacturer. If you're purchasing brand-name Nexium without a prescription, the manufacturer has a $3 coupon available, which you can have emailed to you. Just present it at the register during your purchase.

Why trust our experts?

Written by:

Daphne Berryhill, RPh

Daphne Berryhill, RPh, has two decades of experience as a clinical pharmacist. She spent most of her career in the Chicago area practicing in-home infusion.

Edited by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

Reviewed by:

Stacia Woodcock, PharmD

Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.

Our editorial standards

Meet our experts