Esomeprazole

Generic Name
Esomeprazole
Brand Names
Nexium, Vimovo, Nexium Control
Drug Type
Small Molecule
Chemical Formula
C17H19N3O3S
CAS Number
119141-88-7
Unique Ingredient Identifier
N3PA6559FT
Background

Esomeprazole, sold under the brand name Nexium, is a proton pump inhibitor (PPI) medication used for the management of gastroesophageal reflux disease (GERD), for gastric protection to prevent recurrence of stomach ulcers or gastric damage from chronic use of NSAIDs, and for the treatment of pathological hypersecretory conditions including Zollinger-Ellison (ZE) Syndrome. It can also be found in quadruple regimens for the treatment of H. pylori infections along with other antibiotics including Amoxicillin, Clarithromycin, and Metronidazole, for example. Its efficacy is considered similar to other medications within the PPI class including Omeprazole, Pantoprazole, Lansoprazole, Dexlansoprazole, and Rabeprazole. Esomeprazole is the s-isomer of Omeprazole, which is a racemate of the S- and R-enantiomer. Esomeprazole has been shown to inhibit acid secretion to a similar extent as Omeprazole, without any significant differences between the two compounds in vitro.

Esomeprazole exerts its stomach acid-suppressing effects by preventing the final step in gastric acid production by covalently binding to sulfhydryl groups of cysteines found on the (H+, K+)-ATPase enzyme at the secretory surface of gastric parietal cells. This effect leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus. As the binding of esomeprazole to the (H+, K+)-ATPase enzyme is irreversible and new enzyme needs to be expressed in order to resume acid secretion, esomeprazole's duration of antisecretory effect persists longer than 24 hours.

PPIs such as esomeprazole have also been shown to inhibit the activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme necessary for cardiovascular health. DDAH inhibition causes a consequent accumulation of the nitric oxide synthase inhibitor asymmetric dimethylarginie (ADMA), which is thought to cause the association of PPIs with increased risk of cardiovascular events in patients with unstable coronary syndromes.

Due to their good safety profile and as several PPIs are available over the counter without a prescription, their current use in North America is widespread. Long term use of PPIs such as esomeprazole has been associated with possible adverse effects, however, including increased susceptibility to bacterial infections (including gastrointestinal C. difficile), reduced absorption of micronutrients such as iron and B12, and an increased risk of developing hypomagnesemia and hypocalcemia which may contribute to osteoporosis and bone fractures later in life.

Rapid discontinuation of PPIs such as esomeprazole may cause a rebound effect and a short term increase in hypersecretion. Esomeprazole doses should be slowly lowered, or tapered, before discontinuing to prevent this rebound effect.

Indication

Esomeprazole is indicated for the treatment of acid-reflux disorders including healing and maintenance of erosive esophagitis, and symptomatic gastroesophageal reflux disease (GERD), peptic ulcer disease, H. pylori eradication, prevention of gastrointestinal bleeds with NSAID use, and for the long-term treatment of pathological hypersecretory conditions including Zollinger-Ellison Syndrome.

Associated Conditions
Duodenal Ulcer, Erosive Esophagitis, Gastro-esophageal Reflux Disease (GERD), Heartburn, Helicobacter Pylori Infection, Stress Ulcers, Upper Gastrointestinal Hemorrhage, Zollinger-Ellison Syndrome, Acute benign gastric ulcers, Develop NSAID-induced gastric ulcers, Maintenance of healing Erosive esophagitis, Postendoscopy Bleeding
Associated Therapies
-

Reflux Esophagitis Phase III Study (Initial Treatment)

Phase 3
Completed
Conditions
Interventions
First Posted Date
2008-03-12
Last Posted Date
2010-12-20
Lead Sponsor
AstraZeneca
Target Recruit Count
602
Registration Number
NCT00633932
Locations
🇯🇵

Research Site, Tottori, Japan

Reflux Esophagitis Phase III Study (Maintenance Treatment)

Phase 3
Completed
Conditions
Interventions
First Posted Date
2008-03-12
Last Posted Date
2010-06-17
Lead Sponsor
AstraZeneca
Target Recruit Count
540
Registration Number
NCT00634114
Locations
🇯🇵

Research Site, Tottori, Japan

Prevention of Gastric Ulcers

First Posted Date
2008-03-06
Last Posted Date
2009-03-13
Lead Sponsor
AstraZeneca
Target Recruit Count
504
Registration Number
NCT00629512

Ulcer Prevention II

First Posted Date
2008-03-06
Last Posted Date
2011-01-25
Lead Sponsor
AstraZeneca
Target Recruit Count
800
Registration Number
NCT00629928

Adult Asthmatics and Acid Reflux

Phase 2
Completed
Conditions
Interventions
First Posted Date
2008-03-05
Last Posted Date
2009-03-13
Lead Sponsor
AstraZeneca
Target Recruit Count
1400
Registration Number
NCT00628953

Chronic Posterior Laryngitis With Suspected Laryngopharyngeal Reflux

First Posted Date
2008-03-05
Last Posted Date
2011-01-25
Lead Sponsor
AstraZeneca
Target Recruit Count
120
Registration Number
NCT00628667
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