Nexium vs Prilosec: What's the difference?

Published May 12th, 2020 by Bridget Reed
Fact Checked by
Chris Riley
Updated Date: Jun 9th, 2021

The International Foundation for Gastrointestinal Disorders estimates that anywhere from 15 to 30 percent of Americans suffer from gastroesophageal reflux disease, or GERD. GERD is characterized by the experience of heartburn or indigestion at least twice per week, and it is believed that a number of factors, including the rising obesity rates, influence the skyrocketing rates of GERD in the United States, as people who are overweight or obese are more likely to suffer from GERD. For some people, lifestyle changes or lifestyle changes combined with over the counter antacid medications like Pepcid and Tagamet offer enough relief from their mild to moderate occasional symptoms. People with more severe or more persistent GERD may need to make lifestyle changes and take a different kind of medication or a prescription drugs to treat their symptoms. Nexium and Prilosec are both former prescription-only medications that are now sold at some strengths over the counter and offer relief for sufferers of GERD. 

Drug Class

Nexium, sold under the generic name esomeprazole, and Prilosec, sold under the generic name omeprazole, both belong to a class of medications called proton pump inhibitors (PPIs). The chemical compositions of both medications are slightly different, as Prilosec contains two isomers (chemical compounds that have the same formula but differ in the arrangement of their atoms) of omeprazole, while Nexium contains one. Both medications were originally available only by prescription, but today, both drugs are available over the counter at certain strengths and are also available by prescription at higher strengths. Nexium and Prilosec are two of the most commonly prescribed PPIs on the market today. 

Conditions Treated

Nexium and Prilosec both treat similar conditions, including GERD, Zollinger-Ellison Syndrome, stomach ulcers, duodenal ulcers, erosive esophagitis, and other digestive conditions. 

Gastroesophageal Reflux Disease

Gastroesophageal reflux disease, also known as GERD or heartburn, is a condition characterized by erosive  gastric acid and digestive enzymes flowing backward from the stomach into the esophagus. It’s normal to experience heartburn or acid reflux on occasion, but people with gastroesophageal reflux disease experience these symptoms multiple times per week over a prolonged period of time. GERD usually results from dysfunction in the esophageal sphincter, which is a muscular ring that seals off the esophagus from the stomach in order to prevent food and acid from coming back up into the esophagus. However, in people with GERD, the esophageal sphincter may not function properly or seal tightly enough. If the esophageal sphincter does not seal properly, the sphincter remains relaxed between swallows, allowing food and digestive juices to enter the esophagus. The high acidity of stomach acid can cause damage to the esophagus, including inflammation, narrowing, development of open sores, or a condition called Barrett’s esophagus, which has an increased risk of esophageal cancer. People with GERD often experience some or all of the following symptoms:

  • Tightness in the chest or upper abdomen
  • Regurgitation
  • Difficulty swallowing
  • Hoarseness
  • Nausea
  • A repeated sour or bitter taste in the mouth
  • Sharp or burning pain behind the breast bone
  • Sore throat
  • Coughing, wheezing or needing to clear your throat

Zollinger-Ellison Syndrome

People with Zollinger-Ellison syndrome experience tumors forming in the pancreas or upper small intestines. These tumors secrete large amounts of a hormone called gastrin, which directs too much acid production in the stomach. Peptic ulcers, diarrhea, and other symptoms can be caused by the extra acid.  Although most people are diagnosed between the ages of 20 and 50, the disease may present at any time in life. Symptoms associated with Zollinger-Ellison syndrome include:

  • Diarrhea
  • Acid reflux and heartburn
  • Bleeding in the digestive tract
  • Abdominal pain
  • Burning, aching, or discomfort in the upper abdomen
  • Nausea and vomiting
  • Decreased appetite

How it Works

Proton pump inhibitors, or PPIs, like Nexium and Prilosec work on the enzymes found in the parietal cells of the stomach, called proton pumps. These enzymes make hydrochloric acid, which is the primary component of stomach acid. PPIs work by decreasing the amount of acid made by proton pumps, bringing acidity levels down and preventing the creation of excess acid. Proton pump inhibitors were first introduced in 1981 and are considered the most effective class of medications for reducing stomach acid.

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Dosing medications for both Nexium and Prilosec are similar; most adults will take between 20 to 40 mg once or twice daily for control of symptoms associated with GERD and other digestive conditions. Nexium is available over the counter in capsules, mini capsules, and tablets at 20 mg strength, and it is available by prescription in the form of delayed-release capsules, suspension, packets, and injections. Prilosec is available over the counter in the form of 20 mg strength delayed-release tablets and is available by prescription in the form of delayed-release capsules and suspension. Most people take Nexium for a period of time ranging from ten days to six months, but many patients with chronic GERD continue to take the medication for much longer. Prilosec is typically taken for anywhere from ten days to eight weeks, but patients with chronic GERD often take this medication for longer as well.



While Nexium and Prilosec are both effective drugs for the treatment of GERD and other digestive conditions, some studies have shown that Nexium works more quickly, provides more effective acid control, and lasts for longer than Prilosec. However, other studies have shown no major differences between the two medications. It is believed that Nexium is less likely to produce drug interactions than Prilosec because the medication is broken down differently by the liver. 


While common side effects associated with PPI use, such as diarrhea, nausea, vomiting, or headache, are uncommon, Prilosec is less likely to cause them than Nexium. Prilosec has been on the market longer than Nexium and is usually less expensive than Nexium in its brand name form, although both medications have comparable prices in their generic versions.


Proton pump inhibitors like Nexium and Prilosec do have some risks associated with long term use of the medication. Use of PPIs for a prolonged period of time (longer than the indicated dosing period) may increase the risk of the following conditions:

  • Bone weakening conditions, such as osteoporosis, leading to bone fractures in the spine and wrist in postmenopausal women, particularly when taken for a year or more at a high dose
  • Bacterial inflammation of the colon (Clostridium difficile-associated diarrhea)
  • Pneumonia
  • Nutritional deficiencies, such as vitamin B-12 and magnesium deficiencies
  • Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) 
  • Fundic gland polyps
  • Kidney disease and other problems

Some groups of people are considered more likely to experience negative effects associated with the long term use of PPIs. Risk factors include:

  • Being of Asian descent, as the body may require a different dosage due to a longer length of time needed to process PPIs
  • History of liver disease
  • History of low magnesium levels
  • Being pregnant or planning to become pregnant
  • Breastfeeding

Side Effects

Side effects for both medications are unlikely, but side effects are slightly more likely to occur when taking Nexium as compared to Prilosec otc. Side effects associated with both medications include:

  • Diarrhea
  • Nausea
  • Vomiting
  • Headache
  • Increased risk of heart attack

Drug Interactions

Certain drugs and supplements should not be taken with either Nexium or Prilosec. These medications include:

  • Clopidogrel
  • Nelfinavir
  • Rilpivirine
  • St. John’s wort
  • Delavirdine
  • Rifampin
  • Risedronate

Other drugs may interact with Nexium or Prilosec but can be taken with them under certain conditions. Make sure to tell your medical professional if you are taking any of the following medications:

  • Amphetamine
  • Atazanavir
  • Bosentan
  • Cilostazol
  • Clozapine
  • Dextroamphetamine
  • Antifungal drugs
  • Iron
  • Mesalamine
  • Methylphenidate
  • Raltegravir
  • Tacrolimus
  • Voriconazole
  • Aripiprazole
  • Bisphosphonates
  • Carvedilol
  • Citalopram
  • Cyclosporine
  • Escitalopram
  • Fosphenytoin
  • Hydrocodone
  • Methotrexate
  • Phenytoin
  • Saquinavir
  • Warfarin or other vitamin K antagonists

Use in Pregnant and Breastfeeding Women


Nexium is considered an FDA Class B medication for pregnant women, meaning that no harm has been shown to occur to an unborn child when taken during pregnancy. However, the manufacturer advises that each woman speak with their doctor for medical advice before taking any new medications during pregnancy. The use of Nexium while breastfeeding has not been studied, but studies have been performed for similar medications, like Prilosec. These studies have shown that while PPIs do pass through breast milk to a nursing infant, no negative side effects have been demonstrated, and the amount that passes through the breast milk is less than the prescribed dose given to infants of the same age. 


Prilosec is an FDA Category C medication for pregnant women, meaning that the effects of the medication on developing fetuses has not been conclusively studied.  However, the manufacturer advises that each woman speak with their doctor to determine if the benefit of taking Prilosec during pregnancy may outweigh the risk. Prilosec is generally considered safe to use while breastfeeding, as studies have shown that while PPIs do pass through breast milk to a nursing infant, no negative side effects have been demonstrated, and the amount that passes through the breast milk is less than the prescribed dose given to infants of the same age. Some infants suffer from acid reflux and receive a small dose of Zantac as treatment for the condition; the dose given to infants is less than the amount that passes through breast milk.

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