Differences between Nexium and Prilosec

The most frequently asked question about Nexium is whether this drug is actually different from Prilosec. Nexium (Esomeprazole) is a proton pump inhibitor (PPI) used to reduce gastric acid production and treat various conditions such as gastroesophageal reflux disease (GERD), dyspepsia and peptic ulcers 1. Back in 1989, its older mirror drug Prilosec (Omeprazole) was approved by the Food and Drug Administration (FDA), and it was widely considered as a true pharmacological marvel. Proton pump inhibitors rapidly became a staple drug in clinical practice thanks to their effectiveness and safety. Not only they were able to treat all those conditions related to the excessive production of stomach acid, but they were also available in various dosage forms such as the injectable and oral ones. Shortly after they were discovered, they were also found to be effective to protect patients from the side effects of another widely prescribed drug group: the nonsteroidal anti-inflammatory drugs (NSAID). PPIs can, in fact, prevent gastrointestinal bleedings caused by the action of other medications 2. All medicinal products in this group may inhibit acid secretion by up to 99% by irreversibly blocking the H+ proton pump of the gastric parietal cells. PPIs are widely sold as over the counter medications (OTC) to treat simple conditions such as heartburn and are far more effective than the other antacid drugs such as the H2 antagonist cimetidine 3.


How much is Nexium overpriced when compared to Prilosec?

Esomeprazole is almost the same molecule as omeprazole, an anti-ulcer drug that AstraZeneca actually marketed worldwide for more than ten years. It was so popular that in 2000 Prilosec was the top-selling prescription medicine in the U.S., with retail sales of $4.1 billion 4. So, how can AstraZeneca convince the entire nation that that paying seven times more for something consumers already had was a good idea?
As soon as Prilosec’s patent expired in February 2001, the British company received FDA’s approval to market their brand new drug Nexium (esomeprazole) since it was purported as “more effective” than its predecessor 5. Other pharmaceutical companies rapidly flooded the market with dozens of generic alternatives to omeprazole, causing its market price to fall. However, thanks to the newly patented medication, AstraZeneca’s yearly profits did not suffer at all. According to the American Society of Health-System Pharmacists, today the price for a single unit of generic omeprazole is about $1 per 20 mg capsule. Surprisingly enough, the price of a single dose of generic esomeprazole is seven times higher with an outstanding $7 per 20 mg capsule 6, 7.  The price of branded Nexium may reach up to $15 per 20 mg capsule, instead 8.


The (lack of) differences between Nexium and Prilosec

Did American consumers really need a new drug? How is the newer esomeprazole different from its older brother omeprazole? Simply put, it isn’t. Omeprazole is a mixture of the two chemical species called R- and S- enantiomers, while esomeprazole is just the purified active (S)-enantiomer. In simpler terms, the two R- and S- molecules are entirely identical except for the fact that they’re mirror images of each other, just like the left and right hand. The two enantiomers share the same chemical and physical properties. However, their physiologic activity may change since the biological receptors they are supposed to bind to are usually very selective for just one of them (in this case the S- one). Keeping with our previous metaphor, it’s just like if human cells just want to “shake their hands” with a specific hand, the left one in this specific case.

So, in theory, because omeprazole is composed by 50% (S)-enantiomer (biologically active, i.e. the left hand) and 50% R-enantiomer (biologically inactive, i.e. the right hand), an equivalent dose of 100% S-enantiomer esomeprazole should be twice as effective, right? Wrong. Once the drug reaches the blood after ingestion or injection, a series of in vivo reactions convert all the inactive (R)-enantiomer to the active (S)-enantiomer, so both omeprazole and esomeprazole share the same activity 1. Except for a small number of individuals (about 2% of the population) who can’t do convert one molecule into the other for genetic reasons, all right hands are transformed into left hands shortly after the drug is administered 9.

How is it possible then that the FDA granted AstraZeneca the approval to market Nexium as a new drug? Following patent laws, esomeprazole could not be patented twice since it has the same active ingredient found in Prilosec. Even in the studies that allegedly demonstrated the alleged superiority of Nexium over Prilosec in treating gastroesophageal reflux, omeprazole was able to heal up to 87% of total patients while esomeprazole showed a 90% healing rate after a two months period. Therefore, the difference between healing rates was quite tiny (less than 3%) 10, 11. Although a mere 3% is technically an improvement, but can how such a small difference justify the fact that the pharmaceutical company charged consumers with a sevenfold higher price?

AstraZeneca effectively patented the same drug twice, thus doubling the time their drug can avoid competition from generic medications. Nexium was used in higher dosages than its “competitor” during trials, as the American physiologist and former editor-in-chief of the New England Journal of Medicine Marcia Angell explained in 2007. Researchers from AstraZeneca did, in fact, compare 20 mg Prilosec with both 20 mg and 40 mg Nexium at the same time, effectively distorting the results in favor of esomeprazole’s purportedly superior efficacy 12. In an interview with the New York Times, the chief of the Centers for Medicare and Medicaid Services Thomas A. Scully explained how the pharmaceutical company used the new patent to artificially inflate the drug’s price and overcharge American citizens 13.
Article written by: Dr. Claudio Butticè, Pharm.D.

Published: 2016/07/28
Last Updated: 2016/07/28