Prilosec vs. Nexium comparison

Prilosec (omeprazole) and Nexium (esomeprazole) are used to treat gastroesophageal reflux disease (GERD) and other digestive conditions related to overproduction of stomach acid. These drugs are part of a family of medications called proton pump inhibitors or PPIs, which hinder gastric glands from making acid at a cellular level.

Other PPIs include:

Omeprazole and esomeprazole are nearly identical on a chemical level, so they have all the same side effects and drug interactions. Esomeprazole is the newer medication. Researchers started with omeprazole, and then tinkered with how the molecules were stuck together. As a result, they came up with esomeprazole, which is usually much more potent than omeprazole, despite the slight chemical difference.

Side effects of these drugs are usually mild, but they can include diarrhea, nausea, vomiting, headaches and others. Doctors also try to avoid prescribing PPIs long-term because they interfere with the body's ability to absorb vitamin B12 and cause lower magnesium levels. Long-term users can develop skeletal problems and be more prone to heart attacks.

What are Prilosec and Nexium?

Prilosec and Nexium are proton pump inhibitors or proton pump antagonists. Proton pumps are the mechanisms that squirt out components of hydrochloric acid (hydrogen and chloride ions) into the stomach from the gastric glands to be used for digestion.

The proton pump is a sort of valve made of a molecule of protein on certain stomach cell (parietal cell) membranes. The precise name of the proton pump protein is adenosine triphosphatase or ATPase. It's called a "proton pump" because it actively grabs positively charged atoms of hydrogen from within the cell and "pumps" them into the stomach cavity by switching them with potassium molecules. In the ducts of the gastric glands, the hydrogen ions combine with chloride ions to form hydrochloric acid, which is necessary to digest food. Chloride ions are also secreted by parietal cells, which suck them up from the bloodstream and secrete them through a different channel than the hydrogen ions.

It's important for the proton pump to shoot the hydrogen out of the parietal cell before it turns into acid. Gastrointestinal lining is the only tissue in the body built to handle potentially lethal hydrochloric acid. If the parietal cell manufactured hydrochloric acid inside itself -- as cells do when they make most other compounds -- the acid would kill the cell, digesting it from the inside out instead of digesting the pork chop you just ate.

The molecules of omeprazole and esomeprazole plug up the "valve" of the proton pump, meaning it can't release hydrogen ions into the stomach, which results in less acid.

Esomeprazole -- the newer, more advanced of the two -- is an isomer of omeprazole. This means it's got all the same types and numbers of atoms in the molecule, they're just stuck together in a different way, so Prilosec and Nexium are nearly identical on a chemical level. That slight structural change makes a difference, though. If we continue thinking of the proton pump as a valve, Nexium forms a tighter seal when it plugs up the proton pump. The result is that even a double dose of Prilosec isn't as effective at acid control as a single dose of Nexium, according to a 2002 study.

PPIs are more effective than older H2R antagonists/blockers like famotidine. H2R blockers plug up a protein on parietal cell outer membranes that is set up to receive the messenger chemical called histamine, which is used to initiate all sorts of processes throughout the body. When histamine is inserted into the receptor protein -- called the H2 receptor -- it begins the process of acid production. PPIs -- which stop acid production in the final step rather than the first step -- tend to do a better job at acid control, partly because people quickly develop a tolerance for H2R antagonists after repeated dosing, according to a 2014 study.

Antacids like Pepto Bismol (bismuth), Rolaids, or Tums (calcium carbonate) work completely differently than either PPIs or H2R antagonists. Antacids mix with and neutralize stomach acid after it's already in the stomach cavity. They work fast, but don't last long.


GERD is the back up of stomach acid into the esophagus. See Answer

What are the uses for Prilosec and Nexium?

Omeprazole an esomeprazole are used for treating acid-induced inflammation and ulcers of the stomach and duodenum; gastroesophageal reflux disease (GERD); erosive esophagitis, heartburn; prevention of upper gastrointestinal bleeding in critically ill patients; and Zollinger-Ellison Syndrome. It also is used in combination with antibiotics for eradicating H. pylori infection of the stomach. Over-the counter (OTC) omeprazole is used for treatment of frequent heartburn.

What are the side effects of Prilosec and Nexium?

Omeprazole and esomeprazole, like other PPIs, are well-tolerated. The most common side effects are

Rarely, Prilosec or Nexium can cause nervousness, abnormal heartbeat, muscle pain, weakness, leg cramps, and water retention.

Proton pump inhibitors may increase the risk of Clostridium difficile infection. High doses and long-term use (1 year or longer) may increase the risk of osteoporosis-related fractures of the hip, wrist, or spine. Prolonged use also reduces absorption of vitamin B12 (cyanocobalamin).

Long-term use of PPIs has also been associated with low levels of magnesium (hypomagnesemia). Analysis of patients taking PPIs for long periods of time showed an increased risk of heart attacks.

Therefore, it is important to use the lowest doses and shortest duration of treatment necessary for the condition being treated. Ask your doctor how long you should take your medication


Digestive Disorders: Common Misconceptions See Slideshow

How should Prilosec and Nexium be taken (dosage)?


  • For ulcers, GERD, erosive esophagitis and eradication of H. pylori the recommended dose for adults is 20-40 mg daily. Ulcer healing usually occurs within 4-8 weeks.
  • H. pylori infections are treated for 10-28 days.
  • The usual dose for prevention of upper gastrointestinal bleeding in critically ill patients is 40 mg daily for 14 days.
  • Prilosec OTC is used for treating heartburn for up to two weeks, and the usual dose is 20 mg daily.
  • For the management of Zollinger-Ellison Syndrome the starting dose for adults is 60 mg daily, and the dose is adjusted based on either the response of symptoms or the actual measurement of acid production. Doses greater than 80 mg should be divided. Doses up to 120 mg three times a day have been used in the treatment of Zollinger-Ellison Syndrome.

For maximal efficacy, omeprazole tablets should be taken before meals, swallowed whole and should not be crushed, chewed or opened.


  • For GERD, 20 or 40 mg of esomeprazole is given once daily for 4-8 weeks. In children ages 1-11, the dose is 10 or 20 mg daily.
  • For the treatment of H. pylori, 40 mg is administered once daily in combination with amoxicillin and clarithromycin for 10 days.
  • Frequent heartburn is treated with 20 mg daily for 14 days.
  • The dose for preventing NSAID-induced ulcers is 20 to 40 mg daily for 6 months.
  • Zollinger-Ellison syndrome is treated with 40 mg twice daily.

Esomeprazole capsules should be administered one hour before meals, swallowed whole and should not be crushed or chewed. Patients with difficulty swallowing can open the capsule and mix the pellets with applesauce. The applesauce should not be hot and the pellets should not be chewed or crushed.

Subscribe to MedicineNet's General Health Newsletter

By clicking Submit, I agree to the MedicineNet's Terms & Conditions & Privacy Policy and understand that I may opt out of MedicineNet's subscriptions at any time.

Which drugs interact with Prilosec and Nexium?

Because they are nearly identical at a molecular level, both omeprazole and esomeprazole have negative interactions with the same list of medications.

Both Prilosec and Nexium potentially increase the concentrations in blood of diazepam (Valium), warfarin (Coumadin), and phenytoin (Dilantin) by decreasing the elimination of these drugs by the liver.

The absorption of certain drugs may be affected by stomach acidity. Therefore, omeprazole, esomeprazole, and other PPIs reduce the absorption and concentration in blood of ketoconazole (Nizoral) and increase the absorption and concentration in blood of digoxin (Lanoxin). This may reduce the effectiveness of ketoconazole or increase digoxin toxicity.

Through unknown mechanisms, omeprazole and esomeprazole may increase blood levels of saquinavir and reduce blood levels of nelfinavir and atazanavir, drugs that are used for treating patients with infection caused by the human immunodeficiency virus (HIV). Accordingly, the dose of saquinavir may need to be reduced to avoid toxicity, and the doses of nelfinavir and atazanavir may need to be increased to maintain efficacy.

Clopidogrel (Plavix) is converted to its active form by enzymes in the liver. Both Prilosec and Nexium reduce the activity of these enzymes and potentially can reduce the activity of clopidogrel. Neither omeprazole nor esomeprazole should be used with clopidogrel.

Omeprazole and esomeprazole increase the concentration of cilostazol (Pletal). The dose of cilostazol should be reduced from 100 mg twice daily to 50 mg twice daily when given with omeprazole.

Prilosec and Nexium may increase blood levels of methotrexate (Rheumatrex, Trexall) and tacrolimus (Prograf).

Are Prilosec and Nexium safe to take during pregnancy or while breastfeeding?

There aren't any studies to show whether or not omeprazole or esomeprazole have any effects on a developing fetus. If you're a pregnant woman and you need to take a PPI, do so under the supervision of a doctor (consult your OB/GYN) to help you decide whether the benefits outweigh the risks. Don't take either Prilosec or Nexium while breastfeeding; both medications are secreted in breast milk and could cause problems for the baby.


Prilosec (omeprazole) and Nexium (esomeprazole) are both proton pump inhibitors (PPIs) used to control production of stomach acid. Overproduction of stomach acid is a chief factor in gastroesophageal reflux disease (GERD) and other digestive disorders. Prilosec and Nexium are nearly identical on a molecular level, but Nexium is the more potent medication. Learn about dosages, side effects, and pregnancy safety information for these medications.

Treatment & Diagnosis

Medications & Supplements

Prevention & Wellness

Health Solutions From Our Sponsors

FDA Logo

Report Problems to the Food and Drug Administration

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

Medically reviewed by John P. Cunha, DO, FACOEP; Board Certified Emergency Medicine


Omeprazole Compound Summary

Esomeprazole Compound Summary

FDA Prescribing Information

"The Parietal Cell: Mechanism of Acid Secretion"
Vivo Biomedical HyperText Books
Colorado State University

"Kir4.1 Channel Expression Is Essential for Parietal Cell Control of Acid Secretion"
Penghong Song et al
Journal of Biological Chemistry; March, 2011

"Morphological and functional transformation of the gastric parietal cell between resting and secreting states"
John G. Forte
Department of Cell and Molecular Biology, University of California, Berkely

"Pharmacology of Proton Pump Inhibitors"
National Prescribing Service of Australia

"Effect of esomeprazole 40 mg vs omeprazole 40 mg on 24-hour intragastric pH in patients with symptoms of gastroesophageal reflux disease."
Röhss K, Hasselgren G, Hedenström H.
Digestive Diseases and Sciences; May, 2002

"A review of esomeprazole in the treatment of gastroesophageal reflux disease (GERD)"
Evangelos Kalaitzakis and Einar Björnsson
Journal of Therapeutics and Clinical Risk Management

"Active Transport by ATP-Powered Pumps"
Lodish H, Berk A, Zipursky SL, et al.
Molecular Cell Biology, 4th Edition

"Histamine2-receptor antagonists: Rapid development of tachyphylaxis with repeat dosing"
Johnson W McRorie, James A Kirby, and Philip B Miner
World Journal of Gastrointestinal Pharmacology and Therapeutics; May, 2014

"The alkaline tide phenomenon"
Niv Y, Fraser GM.
Journal of Clinical Gastroenterology; July 2002

"Animation: Hydrochloric Acid Production in the Parietal Cells in the Gastric Glands of the Stomach"
McGraw Hill Companies
Essentials of Anatomy and Physiology, Sixth Edition