Overview
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
Research Report
Comprehensive Monograph: Esomeprazole (DB00736)
Executive Summary
Esomeprazole (DrugBank ID: DB00736) is a highly utilized small molecule drug belonging to the proton pump inhibitor (PPI) class of medications. It functions as a potent and long-acting inhibitor of gastric acid secretion. Chemically, esomeprazole is the pure (S)-enantiomer of omeprazole, a distinction that forms the basis of its pharmacokinetic profile and marketing as a "chiral switch" product.[1] Its primary mechanism of action involves the irreversible inhibition of the hydrogen-potassium adenosine triphosphatase (
H+/K+-ATPase) enzyme system—the gastric proton pump—located in the secretory canaliculi of gastric parietal cells.[1] As a prodrug, esomeprazole requires activation in the acidic environment of the parietal cell, where it is converted to a reactive sulfenamide that covalently binds to and inactivates the pump, thereby blocking the final step in acid production.[5] This irreversible binding results in a pharmacodynamic effect that lasts over 24 hours, far exceeding its plasma half-life and allowing for convenient once-daily dosing.[1]
The medication is indicated for a wide range of acid-related disorders. Key approved uses include the treatment of gastroesophageal reflux disease (GERD), both for symptomatic relief and for the healing and maintenance of erosive esophagitis (EE).[1] It is also a critical component of triple-therapy regimens for the eradication of
Helicobacter pylori to reduce the risk of duodenal ulcer recurrence, and it is used for the prevention of gastric ulcers associated with chronic nonsteroidal anti-inflammatory drug (NSAID) therapy.[9] Furthermore, it is employed in the management of pathological hypersecretory conditions such as Zollinger-Ellison syndrome.[1]
Clinical Trials
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Title | Posted | Study ID | Phase | Status | Sponsor |
---|---|---|---|---|---|
2023/05/03 | Phase 3 | Completed | |||
2023/04/24 | Phase 1 | Completed | |||
2023/02/24 | Phase 4 | Completed | Xijing Hospital of Digestive Diseases | ||
2023/02/14 | Phase 4 | Not yet recruiting | Shanghai East Hospital | ||
2023/01/27 | Phase 4 | Recruiting | |||
2023/01/18 | Phase 1 | Completed | |||
2022/12/12 | Phase 4 | Active, not recruiting | Zhang Xiaofeng,MD | ||
2022/10/21 | Phase 4 | Recruiting | First People's Hospital of Hangzhou | ||
2022/10/17 | Phase 4 | Recruiting | |||
2022/07/20 | Phase 1 | Completed |
FDA Drug Approvals
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Approved Product | Manufacturer | NDC Code | Route | Strength | Effective Date |
---|---|---|---|---|---|
Somerset Therapeutics, LLC | 70069-814 | ORAL | 20 mg in 1 1 | 11/24/2023 | |
A-S Medication Solutions | 50090-3031 | ORAL | 40 mg in 1 1 | 1/7/2021 | |
Somerset Therapeutics, LLC | 70069-815 | ORAL | 40 mg in 1 1 | 11/24/2023 | |
CSPC Ouyi Pharmaceutical Co., Ltd. | 24075-0700 | ORAL | 20 mg in 1 1 | 3/7/2022 | |
Proficient Rx LP | 71205-143 | ORAL | 40 mg in 1 1 | 7/1/2022 | |
Aphena Pharma Solutions - Tennessee, LLC | 71610-665 | ORAL | 40 mg in 1 1 | 10/5/2022 | |
DirectRX | 61919-834 | ORAL | 40 mg in 1 1 | 10/20/2015 | |
Quality Care Products, LLC | 83008-016 | ORAL | 40 mg in 1 1 | 4/20/2023 | |
Proficient Rx LP | 63187-964 | ORAL | 20 mg in 1 1 | 2/1/2023 | |
Graviti Pharmaceuticals Private Limited | 69844-031 | ORAL | 20 mg in 1 1 | 8/17/2023 |
EMA Drug Approvals
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NMPA Drug Approvals
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PPB Drug Approvals
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