Esomeprazole
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Esomeprazole: From Peptic Ulcer Disease to Duodenogastric Reflux
One-Sentence Summary
Esomeprazole is a proton pump inhibitor originally used for acid-related conditions such as peptic ulcer disease, gastroesophageal reflux disease, and Zollinger-Ellison syndrome. The TxGNN model predicts it may be effective for duodenogastric reflux, but this top-ranked prediction is supported by 0 clinical trials and only 1 general review. The strongest evidence in this candidate set is for the closely related, already-established indication of duodenal ulcer, which has more than 30 registered trials and 19 publications.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Peptic ulcer disease, gastroesophageal reflux disease, esophagitis, Zollinger-Ellison syndrome (the Singapore licence records contain no approved-indication text) |
| Predicted New Indication | Duodenogastric reflux |
| TxGNN Prediction Score | 99.53% |
| Evidence Level | L4 (preclinical or mechanism-level only; no trials) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 16 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, esomeprazole is a proton pump inhibitor. It blocks the gastric H+/K+ ATPase and strongly suppresses gastric acid. Its efficacy in acid-related disease is well established.
Duodenogastric reflux is the backflow of duodenal contents (bile and pancreatic juice) into the stomach. Acid suppression may reduce the mucosal injury and symptoms that refluxed material causes. However, bile and pancreatic reflux is largely acid-independent, so any benefit is probably symptomatic and partial. The only supporting source is a general PPI review (PMID 18679668), which has no disease-specific data. This prediction is therefore plausible but unproven.
By contrast, the prediction for duodenal ulcer is effectively an established use, close to the original label. It is supported directly by completed Phase 3 trials and is covered in the evidence sections below.
Clinical Trial Evidence
Top prediction (duodenogastric reflux): Currently no related clinical trials registered.
Best-supported related prediction (duodenal ulcer, 99.40%): the table lists the most relevant of the 31 registered trials.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00633932 | Phase 3 | Completed | 602 | Esomeprazole 20 mg and 40 mg vs omeprazole 20 mg for 8-week healing of reflux esophagitis (double-blind) |
| NCT00633672 | Phase 3 | Completed | 400 | Nexium 40 mg and 20 mg vs ranitidine for healing NSAID-associated gastric ulcers |
| NCT00401752 | Phase 3 | Completed | 397 | Esomeprazole 20 mg vs ranitidine for NSAID-associated gastric ulcer healing |
| NCT00542789 | Phase 3 | Completed | 343 | Esomeprazole 20 mg vs placebo for preventing gastric and/or duodenal ulcers with daily NSAID use |
| NCT00629928 | Phase 3 | Completed | 800 | Nexium 40 mg and 20 mg vs placebo for preventing gastric and duodenal ulcers with NSAID use |
| NCT01069939 | Phase 3 | Completed | 427 | Esomeprazole 20 mg vs placebo for preventing ulcers with continuous low-dose aspirin |
| NCT01142245 | Phase 3 | Completed | 263 | IV and oral esomeprazole for preventing recurrent bleeding from peptic ulcers after endoscopic therapy |
| NCT02296021 | Phase 4 | Completed | 612 | Berberine-containing vs bismuth-containing esomeprazole quadruple therapy for H. pylori eradication |
| NCT06850480 | Phase 3 | Recruiting | 356 | Zastaprazan vs Nexium in reflux esophagitis (esomeprazole is the comparator; no results yet) |
| NCT07312370 | Phase 4 | Not yet recruiting | 120 | IV esomeprazole plus sucralfate for ulcer healing after gastric endoscopic submucosal dissection |
Several of these trials address reflux esophagitis or NSAID-associated ulcers rather than duodenal ulcer itself, so they support the acid-related ulcer setting indirectly.
Literature Evidence
Top prediction (duodenogastric reflux):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 18679668 | 2008 | Review | Eur J Clin Pharmacol | General update on PPI clinical use and pharmacokinetics; no duodenogastric reflux data |
Related prediction (duodenal ulcer):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 11742194 | 2001 | RCT | Eur J Gastroenterol Hepatol | One week of esomeprazole-based triple therapy eradicated H. pylori and healed duodenal ulcer |
| 11121908 | 2000 | RCT | Aliment Pharmacol Ther | One-week esomeprazole triple therapy effectively eradicated H. pylori in duodenal ulcer disease |
| 12093317 | 2002 | Review | Drugs | Esomeprazole gave better acid control than other PPIs and higher healing rates of erosive oesophagitis |
| 18627213 | 2008 | Review | Drugs | Review of esomeprazole in gastric acid-related diseases, including NSAID-associated ulcer and H. pylori-associated duodenal ulcer |
| 22372726 | 2012 | Review | Drugs & Aging | Fixed-dose aspirin/esomeprazole capsule for patients at risk of gastric or duodenal ulcers |
| 16335855 | 2005 | Review | Drugs | PPIs are more effective than H2 blockers for H. pylori eradication, ulcer healing, and NSAID-induced lesions |
| 11060758 | 2000 | Review | Expert Opin Investig Drugs | Update on therapeutic approaches to gastric and duodenal ulcers |
| 10983736 | 2000 | Review | Drugs | Esomeprazole gave better intragastric pH control than comparator PPIs |
Singapore Market Information
Sixteen valid single-ingredient licences are registered, and none has been cancelled. Five main authorizations are listed below. No approved-indication text is recorded for any of them.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN11498P | NEXIUM MUPS TABLET 20 mg (AstraZeneca AB) | Tablet, film coated | Not recorded |
| SIN11499P | NEXIUM MUPS TABLET 40 mg (AstraZeneca AB) | Tablet, film coated | Not recorded |
| SIN12616P | NEXIUM POWDER FOR SOLUTION FOR INJECTION AND INFUSION 40 mg (AstraZeneca) | Injection, powder, for solution | Not recorded |
| SIN15233P | EMANERA GASTRO-RESISTANT CAPSULES 40 MG (Krka) | Capsule | Not recorded |
| SIN14632P | ESOZ TABLETS 20MG (Sun Pharmaceutical) | Tablet, enteric coated | Not recorded |
Available forms include oral capsules and tablets and injectable powders, so both oral and intravenous routes are marketed in Singapore.
Safety Considerations
- Contraindications flagged in the knowledge graph (these come from the model's graph, not label text): liver failure, osteoporosis, postmenopausal osteoporosis, bone fracture, and chronic atrophic gastritis.
- Drug Interactions: 100 interactions were identified. Examples include:
- Major: acalabrutinib, atazanavir
- Moderate: hydrochlorothiazide, amphotericin B, amikacin, amphetamine, fenofibrate, apalutamide, armodafinil, atorvastatin, bendamustine, bosutinib, bumetanide
- Minor: acetylsalicylic acid, axitinib, bortezomib, brivaracetam, cyanocobalamin
- The prediction rationale also flags CYP2C19-related interactions, including with clopidogrel.
Please refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold (for the top-ranked prediction, duodenogastric reflux)
Rationale:
- Duodenogastric reflux has no trials and only one general PPI review, and the mechanism is only partly plausible because bile reflux is largely acid-independent.
- The closely related duodenal ulcer and active peptic ulcer disease predictions each have a "Proceed with Guardrails" rating. Their evidence is strong (several completed Phase 3 trials), but they are established uses, not new repurposing.
To proceed, the following is needed:
- Disease-specific studies of esomeprazole in duodenogastric reflux, such as symptom and endoscopic or histological outcomes in a controlled trial
- Mechanism of action data
- Package insert warnings and contraindications from the Singapore regulator
- For the ulcer indications, guardrails: confirm H. pylori status, review CYP2C19 and clopidogrel interactions, and limit therapy duration
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.