Prilosec vs Nexium vs Prevacid

The U.S. Food and Drug Administration (FDA) approved the first prescription proton-pump inhibitor (PPI) in 1989 as a treatment for heartburn caused by acid reflux. The extended-release drug, based upon the active ingredient omeprazole, was developed by AstraZeneca and marked the beginning of a new and popular class of heartburn drugs.

The most popular OTC proton-pump inhibitors today are:

  • Prilosec OTC (omeprazole) - made by AstraZeneca
  • Nexium (esomeprazole) - made by AstraZeneca
  • Prevacid 24 HR (lansoprazole) - made by Takeda Pharmaceutical Company

Since their introduction to the market, proton pump inhibitors like Prilosec have become one of the most common prescriptions in the United States, accounting for $11 billion worth of pharmaceutical sales yearly. Omeprazole, the active ingredient in Prilosec, has also been on the World Health Organization's Model List of Essential Medicines for almost a decade.

Given the popularity of these drugs, we've put together a comparison of the most popular proton-pump inhibitors to help you understand their relative risks. Though all PPIs function by blocking the final step in stomach acid production, they do have some important differences. Specifically, they differ in their approved uses, side effects, drug interactions, and contraindications (who should not take the drug).

Important: This comparison should not be considered as medical advice. Talk to your doctor or pharmacist about how these acid reflux drugs could affect you.

Prilosec, Nexium and Prevacid Similarities

All PPIs treat excessive acid problems by blocking the action of a proton pump located in gastric parietal cells. This effectively prevents a substantial portion of stomach acid secretion, thereby reducing the overall acidity level in the stomach. According to a large number of studies, including those involved in the drug approval processes, this makes PPIs very effective in treating a variety of acid-related conditions.

Prilosec, Nexium and Prevacid Shared Indications

All three are approved for use in people 1 year of age and older for certain conditions, and the majority of indications are for short term therapy.

  • Erosive esophagitis healing and maintenance
  • Nonerosive reflux disease
  • Zollinger-Ellis Syndrome
  • Treatment of Helicobacter pylori (H pylori) as part of a triple therapy protocol

Common Proton Pump Inhibitor Side Effects

Despite their frequent usage and wide variety of treated conditions, each of these drugs has been associated with serious side effects including an increased risk of acute interstitial nephritis and chronic kidney disease. In acute interstitial nephritis, the spaces between kidney tubules swell and compromise kidney function. If caught early enough and treated properly, most patients can recover from this condition. However, if acute interstitial nephritis goes without treatment for a period of days or weeks, it can cause permanent kidney damage. Patients can find warnings about acute interstitial nephritis on the drug labels for each of these proton pump inhibitors.

Though researchers cannot agree on the biological rationale for it, PPIs seem to increase the risk of a very serious kind of diarrhea associated with Clostridium difficile (C. dif) bacteria. It may sound unbelievable, but this condition can be life-threatening. In fact, according to the Centers for Disease Control, 1 of every 11 people over the age of 65 who acquire a healthcare-associated C. diff infection die within a month of diagnosis. Medical researchers have suggested that patients diagnosed with C. diff associated diarrhea stop taking proton pump inhibitors immediately upon diagnosis.

All three of these drugs seem to interfere with absorption and metabolism of certain nutrients. Daily long-term use of PPIs for longer than three years may lead to poor absorption or deficiency of Vitamin B-12. In rare cases of long-term PPI use, patients may also experience diminished magnesium levels, which can cause a host of symptoms including insomnia.

According to their drug labels, the most common and least serious side effects of PPI usage include headache, nausea, vomiting, flatulence, diarrhea, and abdominal pain. All three of these drugs have been associated with new-onset lupus and fundic gland polyps.

Published studies indicate that the incidence of most proton pump inhibitor side effects increases with length of usage. Physicians involved in these studies encourage patients to use PPIs exactly as prescribed and for the shortest possible amount of time to achieve relief of their gastric acid related symptoms.

Common Proton Pump Inhibitor Contraindications and Warnings

Anyone taking a proton pump inhibitor should know that they can interfere with the diagnosis and treatment of a number of conditions. Many individuals may mistakenly believe that symptom improvement after PPI therapy eliminates gastric cancer as a diagnostic possibility. For this reason, drug labels for Prilosec, Nexium and Prevacid warn patients to seek additional testing for gastric cancer if it was a possible diagnosis.

PPI therapy can also interfere with diagnosis of neuroendocrine tumors. Patients and physicians are instructed to withdraw PPIs for at least 14 days before performing certain laboratory tests for this diagnosis.

As with any drug, patients run the risk of an allergic reaction to the drug itself. Any patient with a known PPI allergy should not take that drug.

Differences Between Prilosec, Nexium and Prevacid

While these three drugs function in the same manner and share many indications and side effects, their chemical structures vary slightly. These slight variations are the most likely cause for the few differences we see in their side effects and approved indications.

Both Prilosec and Nexium interfere with the function of St. John's Wort and rifampin, while Prevacid does not. On the other hand, Prevacid contains phenylalanine, meaning patients with phenylketonuria may want to choose one of the other two.

Neither Prevacid nor Prilosec should be taken by patients receiving rilpivirine products, and Prilosec may interfere with the action of certain antibiotics.

Summary: Prilosec vs Nexium vs Prevacid

Brand Name(s) Unique Properties

Prilosec OTC

Contraindicated With: St. John's Wort, Rifampin, Some Antibiotics

Nexium OTC

Contraindicated With: St. John's Wort, Rifampin

Prevacid 24 HR

Contains: Phenylalanine

Proton Pump Inhibitor Lawsuits

One of the more unfortunate similarities we find for these three drugs is their status as the subject of lawsuits. Patients have filed thousands of lawsuits against pharmaceutical companies after experiencing unexpected and serious side effects from proton pump inhibitor therapy. Federal lawsuits involving PPIs were consolidated in the United States District Court of New Jersey using multidistrict litigation (MDL). As of January 2019, there are more than 2,700 active proton pump inhibitor lawsuits pending in MDL 2789.

Authored by Katy Moncivais, Ph.D.Medical Editor
Photo of Katy Moncivais, Ph.D.
Katy Moncivais holds a Ph.D. in Biomedical Engineering from The University of Texas at Austin. She’s an experienced Regenerative Medicine Consultant with a demonstrated history of working in the hospital & healthcare industry. Skilled in adult stem cells, medical devices, biomechanics, bacterial and mammalian cell culture, and regenerative medicine, she provides guidance on an array of topics affecting consumers. In her role at, Dr. Moncivais works alongside the writing and research staff to help deliver fact-based news stories to consumers. Her unique professional history alongside her rigorous educational background allows her to contribute to a variety of consumer-focused topics with a fresh perspective. In addition, Dr. Moncivais reviews portions of medically driven content to ensure scientific accuracy.
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