Nexium vs Prilosec: What’s the Difference?

By Alicia Wooldridge, MD
Medically reviewed checkmarkMedically reviewed
July 15, 2022

Nexium and Prilosec are two medications that are commonly used for symptoms of heartburn and GERD, which stands for gastroesophageal reflux disease and affects around 20% of all people in the United States. 

While acid reflux or heartburn, sometimes called GERD, may affect people after certain foods or occasionally, GERD is a chronic digestive condition that causes a lot of pain. If left untreated, it can cause health complications.

In this article, we’ll compare these two common heartburn medications, go over which works better, and how to safely use these medicines.

What Is Nexium?

Esomeprazole is the generic name for Nexium. It is a proton pump inhibitor (PPI) that is used for treating heartburn and acid reflux.

Common side effects for Nexium include:

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What Is Prilosec?

Prilosec, the brand name for omeprazole, is also a proton pump inhibitor (PPI). It is used to treat heartburn and acid reflux, too.

Common side effects of Prilosec are:

Nexium vs Prilosec

Both Prilosec and Nexium have similar-sounding generic names because they are made from the same chemicals with slightly different arrangements.

They both work to reduce the symptoms of GERD by blocking acid in the stomach. 

This prevents the backflow of stomach acid through the esophageal sphincter and up the esophagus to the back of the throat, which is what causes the painful burning symptoms associated with acid reflux or heartburn.

Both drugs are approved by the U.S. Food and Drug Administration (FDA) for treating the following conditions:

  • Gastroesophageal reflux disease (GERD)
  • Zollinger-Ellison syndrome

Prilosec is also FDA-approved to treat:

  • Duodenal ulcers and stomach ulcers
  • Esophagitis

Nexium and Prilosec are both available as prescriptions or over-the-counter.

Even if you choose an OTC option, you should still check with a medical provider before you use either Nexium or Prilosec, since they can interact with other medications.

Type of drugProton pump inhibitorProton pump inhibitor
Brand or genericBothBoth
Prescription formsDelayed-release capsules, suspension, injection, packetsDelayed-release capsules, suspension
Over-the-counter formsCapsules, mini capsules, tabletsDelayed-release tablets
Insurance coverageYes, as a generic prescriptionYes, as a generic prescription
Medicare coverageYes, as a generic prescriptionYes, as a generic prescription
Typical copay$14$0-$20
Standard dosage20-40 mg, one or two times per day20-40 mg, one or two times per day


When comparing Nexium to Prilosec, clinical trials found that Nexium tended to outperform Prilosec and other PPIs.

Nexium was able to offer the best acid control as well as faster symptom relief.

Even so, both medicines are effective and one may work better for another based on individual health factors.

Which Is Better

Nexium and Prilosec are both similar drugs, and while Nexium performed better in some aspects of research, they are both considered to be effective treatments for GERD and acid reflux.

A healthcare provider will recommend the medication that works best for your health history, current medical needs, and in consideration of any other medications you take.

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Warnings and Interactions

Nexium and Prilosec are similar drugs, so they have similar warnings and interactions.

Some potentially serious health conditions that can occur with PPI use can include:

  • Clostridium difficile diarrhea
  • Bone fractures, especially in the spine, hip, and wrist
  • Kidney problems or disorders
  • Cutaneous lupus erythematosus
  • Systemic lupus erythematosus
  • Vitamin B12 deficiency after long-term use
  • Serious magnesium deficiency after long-term use

Both drugs have the potential to increase false-positive test results for neuroendocrine tumors.

Nexium and Prilosec use is not recommended for pregnant and breastfeeding persons. They should check with healthcare providers before the use of PPIs.

People who have osteoporosis or are at high risk for developing it should not take Prilosec or Nexium, since it can increase the risk for bone fractures.

Possible drug interactions include:

  • Nexium: Atazanavir, calcium carbonate, clopidogrel, dapsone, indinavir, iron, itraconazole, ketoconazole, mycophenolate, nelfinavir, vitamin B12, methotrexate, tacrolimus, warfarin, cilostazol, clozapine, any CYP2C19 drugs, diazepam, digoxin, penicillins, saquinavir
  • Prilosec: Ampicillin, calcium carbonate, vitamin B12, cycloSPORINE, diazepam, digoxin, disulfiram, flurazepam, gefitinib, indinavir, iron salts, ketoconazole, phenytoin, triazolam, warfarin, citalopram, methotrexate, plavix, St. John’s wort

How K Health Can Help

Now you can treat acid reflux online using K Health for just $29 per month.

Just three easy steps:

  1. Answer a few simple questions.
  2. Meet your provider.
  3. Get the care you need.

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Frequently Asked Questions

Which is better for you, Nexium or Prilosec?
Both Nexium and Prilosec are proton pump inhibitors (PPIs). They work to decrease acid in the stomach and prevent symptoms of acid reflux. Both drugs work similarly. Nexium performed better in some clinical trials, with better short-term results, but both had the same level of effectiveness long term. The best medication for you depends on your health history, other prescriptions you take, and other factors that your healthcare provider will consider when they prescribe a treatment or recommend an OTC drug.
Why does Nexium work better than Prilosec?
Nexium is chemically similar to Prilosec but contains a slightly different isomer profile. This means that while the drugs are very similar, the slightly different arrangement of the ingredients may lead Nexium to work slightly better in the short term. Longer-term studies show equal effectiveness between the two medicines. In the short term, the isomer arrangement of Nexium means that the drug gets metabolized more slowly. This means that Nexium stays in the body longer, which is why it offers slightly better acid control. Because of the chemical makeup, Nexium is likely to cause fewer potential drug interactions than Prilosec.
Is Nexium more effective than omeprazole?
Nexium was shown by some clinical trials to provide faster acid reflux relief and to provide fewer nights with GERD symptoms. However, in the longer term view of the study, both medications performed similarly. Prescribers often consider these two drugs equally and may recommend one over the other for reasons that are specific to your individual health.
Is Nexium similar to Prilosec?
Nexium and Prilosec are in the same drug class. They are both proton pump inhibitors (PPIs) and work to lower the amount of acid in the stomach. The reduced acid can decrease GERD symptoms and provide relief from painful acid reflux.
K Health articles are all written and reviewed by MDs, PhDs, NPs, or PharmDs and are for informational purposes only. This information does not constitute and should not be relied on for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment.

Alicia Wooldridge, MD

Dr. Alicia Wooldridge is a board certified Family Medicine physician with over a decade of experience.

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