Omeprazole
| Evidence Level: L4 | Predicted Indications: 2 |
Table of Contents
Omeprazole: From Gastric Ulcer and Acid-Related Disease to Duodenogastric Reflux
One-Sentence Summary
Omeprazole is a proton pump inhibitor originally used for acid-related conditions such as gastric and duodenal ulcer, gastroesophageal reflux disease (GERD), esophagitis and Zollinger-Ellison syndrome. The TxGNN model predicts it may be effective for duodenogastric reflux, but only 1 registered clinical trial (not directly relevant) and a small body of mostly small-scale or animal literature exist, so the prediction is still at the research-question stage.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Gastric ulcer, peptic ulcer disease, GERD, esophagitis, duodenal ulcer, Zollinger-Ellison syndrome (US label indication text is not available in the data compiled for this report) |
| Predicted New Indication | Duodenogastric reflux |
| TxGNN Prediction Score | 99.64% |
| Evidence Level | L4 |
| US Market Status | Cancelled only (all 10 listed authorizations are cancelled) |
| Number of NDAs | 10 authorizations (2 NDAs, 8 ANDAs) |
| 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 information, omeprazole is a proton pump inhibitor (PPI) that suppresses gastric acid secretion. Its efficacy in acid-related disorders such as GERD, esophagitis and peptic ulcer is well established.
Duodenogastric reflux is closely related to these conditions because it affects the same part of the digestive tract and can damage the mucosa. However, it is driven mainly by bile and pancreatic secretions, not acid. Acid suppression may ease acid-related mucosal symptoms but does not address the bile reflux itself. Small studies in Barrett’s oesophagus and in children with oesophageal bile reflux have looked at omeprazole’s effect on reflux parameters.
There is also a safety signal. Animal studies suggest that acid blockade combined with duodenogastric reflux may promote mucosal growth and gastric carcinogenesis. The very high TxGNN score is a computational prediction, not clinical evidence.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02685150 | N/A (non-interventional) | Completed | 157 | Endoscopic tri-modal imaging to distinguish functional dyspepsia from reflux disease. It does not test omeprazole, so it is not direct evidence for this indication. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 10994616 | 2000 | Clinical study | Scand J Gastroenterol | Effect of omeprazole on antral duodenogastric reflux in Barrett’s oesophagus; earlier work suggested omeprazole may reduce reflux. |
| 9824338 | 1998 | Clinical study | Gut | Omeprazole 20 mg twice daily and its effect on duodenogastric and gastro-oesophageal bile reflux in Barrett’s oesophagus. |
| 16641575 | 2006 | Prospective study | J Pediatr Gastroenterol Nutr | Effect of omeprazole on oesophageal bile reflux in children. |
| 12836018 | 2003 | Clinical series | Eur J Pediatr | Six young patients with primary duodenogastric reflux unresponsive to classical antacid therapy. |
| 18679668 | 2008 | Review | Eur J Clin Pharmacol | Update on clinical use and pharmacokinetics of PPIs; first-choice drugs for ulcer, GERD and Zollinger-Ellison syndrome. |
| 10389684 | 1999 | Animal study | Dig Dis Sci | In rats, gastric acid blockade with omeprazole promoted gastric carcinogenesis induced by duodenogastric reflux. |
| 8943968 | 1996 | Animal study | Dig Dis Sci | Duodenogastric reflux stimulated foregut mucosal growth, potentiated by acid blockade. |
| 33027361 | 2020 | Animal study | Acta Cir Bras | Investigated whether omeprazole protects against gastric adenocarcinoma in rats with duodenogastric reflux. |
| 8076761 | 1994 | Clinical study | Gastroenterology | Relationship of pH to duodenogastroesophageal reflux and its importance in Barrett’s oesophagus. |
No randomized controlled trials were identified.
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA022032 | Omeprazole (Publix Super Markets) | Delayed-release tablet | Not available (cancelled) |
| NDA209400 | Omeprazole (H E B) | Orally disintegrating delayed-release tablet | Not available (cancelled) |
| ANDA212977 | Omeprazole (RemedyRepack) | Delayed-release capsule | Not available (cancelled) |
| ANDA203270 | Omeprazole (Rising Pharma) | Delayed-release capsule | Not available (cancelled) |
| ANDA091672 | Omeprazole (Preferred Pharmaceuticals) | Delayed-release capsule | Not available (cancelled) |
All 10 authorizations in the data are cancelled; the table shows the first 5.
Safety Considerations
- Disease associations from the knowledge graph (not label text): Liver failure, liver disease, gallbladder disease, congestive heart failure, osteoporosis, postmenopausal osteoporosis, bone fracture and chronic atrophic gastritis are linked to omeprazole as contraindication-type relationships. These need verification against the package insert.
- Preclinical signal: Rat studies suggest acid blockade combined with duodenogastric reflux may promote gastric carcinogenesis and mucosal growth. This is directly relevant to the proposed indication.
- Drug Interactions: The interaction query returned 100 records. Examples include:
- Major: Acalabrutinib, Atazanavir
- Moderate: Atorvastatin, Alprazolam, Hydrochlorothiazide, Fenofibrate, Apalutamide, Armodafinil, Amphetamine, Anagrelide, amphotericin B formulations, Amikacin
- Minor: Nifedipine, Lidocaine, Acetylsalicylic acid, Ambrisentan
Package-insert warnings and contraindications are not available in the data compiled for this report. Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests on a high model score and a plausible but indirect link to acid-related disease. There are no relevant interventional trials and no RCTs. The few clinical studies are small, and animal data point to a possible carcinogenesis risk when acid suppression is combined with bile reflux. All US authorizations in the data are cancelled, and label safety information is missing.
To proceed, the following is needed:
- FDA package insert warnings and contraindications (a blocking gap for safety screening)
- Detailed mechanism-of-action data
- Controlled clinical evidence of omeprazole in duodenogastric reflux, with attention to the long-term gastric carcinogenesis signal
- Confirmation of the current US marketing and authorization status
- Review of the knowledge-graph disease associations (hepatic, cardiac, bone) against label text
Note on the second predicted indication (duodenal obstruction)
Duodenal obstruction (TxGNN score 99.64%, evidence level L5, decision Hold) is not supported. It is a mechanical condition, omeprazole has no plausible direct effect on it, and the one linked trial (NCT00557921, a terminated Phase 3 study of clopidogrel plus omeprazole for upper GI bleeding) does not address obstruction. The literature consists of case reports on ulcer, stenosis and Crohn’s disease. The high score likely reflects network proximity to peptic ulcer disease and not a true treatment effect.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.