Omeprazole
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
Omeprazole: Duodenal obstruction
One-Sentence Summary
Omeprazole is a proton pump inhibitor originally used for gastric and duodenal ulcers, reflux disease, oesophagitis and Zollinger-Ellison syndrome.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Duodenal obstruction |
| TxGNN Prediction Score | 0.9964 |
| Evidence Level | L5 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, 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 that suppresses gastric acid secretion. Its efficacy in acid-related upper gastrointestinal disease is established, and mechanistically it may reduce mucosal injury from refluxed duodenal contents.
Small clinical studies in Barrett oesophagus (1998, 2000) and a prospective paediatric study of oesophageal bile reflux (2006) report effects on duodenogastric or bile reflux. However, bile reflux is not acid-driven, so any benefit is likely to be symptomatic rather than disease-modifying.
There is also a safety concern. Three animal studies (1996, 1999, 2020) suggest that acid blockade combined with duodenogastric reflux promotes mucosal growth stimulation and gastric carcinogenesis in rats. These findings have not been shown in humans, but they argue for caution.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT02685150 | N/A | Completed | 157 | Endoscopic tri-modal imaging to distinguish functional dyspepsia from reflux disease. It is a diagnostic imaging study and does not test omeprazole for duodenogastric reflux. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 10994616 | 2000 | Clinical study | Scand J Gastroenterol | Effect of omeprazole on antral duodenogastric reflux in Barrett oesophagus |
| 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 | Omeprazole for oesophageal bile reflux in children |
| 18679668 | 2008 | Review | Eur J Clin Pharmacol | Update on clinical use and pharmacokinetics of PPIs |
| 12836018 | 2003 | Clinical series | Eur J Pediatr | Primary duodenogastric reflux in six children and adolescents, unresponsive to antacid therapy |
| 10389684 | 1999 | Animal study | Dig Dis Sci | Acid blockade with omeprazole promoted gastric carcinogenesis induced by duodenogastric reflux in rats |
| 8943968 | 1996 | Animal study | Dig Dis Sci | Duodenogastric reflux stimulated foregut mucosal growth, potentiated by acid blockade |
| 33027361 | 2020 | Animal study | Acta Cir Bras | Whether omeprazole protects against gastric adenocarcinoma in rats with duodenogastric reflux |
| 8076761 | 1994 | Clinical study | Gastroenterology | Relationship of pH to duodenogastroesophageal reflux in Barrett’s oesophagus |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 11677N | Losec Tablets | Tablet 20 mg (as magnesium) | Not stated in the data compiled |
Safety Considerations
- Contraindications flagged in the knowledge graph (these are graph associations, not label text): liver failure, liver disease, gallbladder disease, congestive heart failure, osteoporosis, postmenopausal osteoporosis, bone fracture, chronic atrophic gastritis.
- Drug Interactions: 100 interactions were recorded. Major interactions in the data reviewed include acalabrutinib and atazanavir. Moderate interactions include hydrochlorothiazide, alprazolam, atorvastatin, fenofibrate, apalutamide, armodafinil, amphetamine, anagrelide, and several amphotericin B and aminoglycoside agents (e.g. amikacin). Minor interactions include lidocaine, nifedipine, ambrisentan and aspirin.
- Animal data: acid blockade combined with duodenogastric reflux promoted mucosal growth and carcinogenesis in rats (see above).
Please also refer to the TGA-approved Product Information (PI) for full warnings and precautions.
Conclusion and Next Steps
Decision: Hold
Rationale: The only registered trial does not test omeprazole, human evidence is limited to small studies in Barrett oesophagus and paediatric bile reflux, and bile reflux is not acid-driven. Animal data also raise a carcinogenesis concern with acid suppression in the presence of duodenogastric reflux.
To proceed, the following is needed:
- Randomised controlled trials of omeprazole in duodenogastric reflux with clear symptomatic or histological endpoints
- Assessment of long-term safety with acid suppression in duodenogastric reflux, given the animal carcinogenesis signals
- Mechanism of action data and TGA Product Information warnings and contraindications, which were not available for this report
- The approved indication text for the Australian licence (ARTG 11677N), which is currently blank
- Review of the major drug interactions (e.g. acalabrutinib, atazanavir) for any proposed use
Other predicted indications (for context): Of the other nine predictions, only two are potentially actionable. Gastrojejunal ulcer (marginal ulcer after bariatric surgery) has the strongest support (L2, with a recruiting Phase 4 trial, NCT05799105). Peptic ulcer perforation (L2) supports acid suppression as adjunct care only. Active peptic ulcer disease is already an approved indication and so is not true repurposing. The mastocytosis subtypes and glucagon secretion predictions have no meaningful evidence.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.