Prilosec Vs. Nexium: What Is The Difference?

Prilosec Vs. Nexium: What Is The Difference?
GERD Title

Proton pump inhibitors (i.e. "PPIs") are a commonly used class of medications for the treatment of heartburn and related disorders such as gastric ulcers and GERD (gastroesophageal reflex disease). Once available by prescription only, there are now many different PPI products available over the counter.

Prilosec (omeprazole) and Nexium (esomeprazole) are two of the most popular medications available. Below, we discuss both in detail and highlight their similarities and differences.

How Do PPI Medications Work?

Proton pump inhibitors (PPIs) cause an overall decrease in gastric acid secretion. They work by inhibiting acid pumps in the stomach, known as the H+/K+ ATPase enzyme system, or informally as "proton pumps". The inhibition of these pumps causes a net decrease in acid secretion which in turn causes a net increase in gastric pH (higher pH signifies less acidity).

An interesting point regarding PPI medications is that only inhibit active proton pumps. It is for this reason that PPI medication should be taken on an empty stomach, about 30 to 60 minutes before food. The medication needs time to be absorbed into our system and ready to act when the proton pumps are active and secreting acid (which occurs when food is consumed).

Prilosec Vs. Nexium: Differences

Prilosec (omeprazole) was the first approved PPI medication in the United States (in 1989) and was also the first to be available over the counter. Nexium (esomeprazole) was approved more recently, in 2001, and the over the counter version was approved in 2014.

You may have noticed the similarity in the generic names of both drugs: omeprazole and esomeprazole. Esomeprazole is simply one isomer that is already contained in Prilosec (omeprazole).


We won't go too in-depth regarding the chemistry of this but it is important to know the following: Isomers are the molecules that are identical in terms of their molecular formula but their atoms are arranged in different ways. Most drug compounds contain two enantiomers (two isomers that are mirror images of one another). Below, you can watch Walter White explain isomerism and their "chiral" nature:



The main difference between Prilosec and Nexium is the following:


  • Prilosec (omeprazole) contains a mixture of two isomers: S-omeprazole and R-omeprazole.
  • Nexium (esomeprazole) contains only the s-omeprazole isomer (thus the name esomeprazole).

While the difference in molecular structure of two isomers may not seem significant, isomerism often plays a significant role in medication effect. We very often see different isomers of one drug compound have significantly different effects in terms of safety, effectiveness and their pharmacokinetic (e.g. absorption rate etc...) profile.

Comparison Studies

While Nexium and Prilosec are very similar in terms of effectiveness, studies do show that Nexium is likely slightly more efficacious.


Studies have shown that Nexium (esomeprazole) is metabolized slower than Prilosec (omeprazole), which leads to higher drug concentrations and prolonged suppression of stomach acid. This may make Nexium more effective in treating symptoms of GERD.  In addition, Nexium appears to be faster acting than Prilosec and may relieve symptoms of heartburn faster.

One study evaluated the acid suppression ability of over the counter PPI medications and Nexium (esomeprazole) came out on top as shown in the below diagram:

Nexium Vs. Prilosec

Source: PubMedPfizer

In addition to the data showing Nexium is better at suppressing acid, studies have also shown that it is slightly more effective in treating related gastrointestinal disorders such as GERD as evidenced in the below chart:

Healing Rates For GERD (Prilosec Vs. Nexium)
Dose Week 4 Week 8
Nexium 20 mg 70% 90%
Nexium 40 mg 56% to 82% 78% to 94%
Prilosec 20 mg 39–81% 74–92%
Prilosec 40 mg 45–81% 75–93%

Source: PubMed

It is important to note that while data suggests that Nexium may be slightly more effective than Prilosec, they are still remarkably similar and most individuals should get similar relief from either product. The correct product choice may simply come down to preference and cost.

Additional Information

  • Over the counter Prilosec is only available in tablet form (20 mg tablets)
  • Nexium is available in capsule form (20 mg capsules)
  • For those who have trouble swallowing, Nexium capsules may be opened and sprinkled on applesauce to ease administration
  • Prilosec is available OTC as the brand name and generic
  • Nexium is available OTC only as the brand name and therefore may be more expensive

Ready for a more personal experience with your meds?