Vonoprazan
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Vonoprazan
- Vonoprazan: From Gastric/Duodenal Ulcer and Reflux Esophagitis to Active Peptic Ulcer Disease
Vonoprazan: From Gastric/Duodenal Ulcer and Reflux Esophagitis to Active Peptic Ulcer Disease
One-Sentence Summary
Vonoprazan is a potassium-competitive acid blocker (P-CAB), originally used for gastric ulcer, duodenal ulcer, esophagitis and gastroesophageal reflux disease. The TxGNN model predicts it may be effective for active peptic ulcer disease, which is essentially an on-label or near-label use. Currently there are 0 registered clinical trials but 18 publications supporting this direction, including systematic reviews, meta-analyses and randomised trials.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Gastric ulcer, duodenal ulcer, esophagitis, peptic esophagitis, gastroesophageal reflux disease (from the knowledge graph; no approved indication text is available in the Singapore licences) |
| Predicted New Indication | Active peptic ulcer disease |
| TxGNN Prediction Score | 99.97% |
| Evidence Level | L1 (see note below) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Proceed with Guardrails |
Note on evidence level: No clinical trials are registered for this indication in the data compiled for this report. The L1 grade rests on published phase 3 RCTs and meta-analyses of vonoprazan in gastric and duodenal ulcers, which are closely related conditions.
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the compiled data. From general pharmacological knowledge, vonoprazan reversibly inhibits gastric H+/K+-ATPase (the proton pump). Unlike proton pump inhibitors, it does not need acid activation. This gives rapid onset, durable 24-hour acid control, and less dependence on meal timing or CYP2C19 variability.
Active peptic ulcer disease covers the same gastric and duodenal ulcers that vonoprazan already treats. This is therefore closer to an on-label use than true repurposing. Acid suppression also supports its role in H. pylori eradication regimens, and the drug is used this way in the US as part of dual and triple packs.
Evidence in ulcer settings is mixed in places. A 2024 meta-analysis notes that efficacy for gastric and duodenal ulcers versus PPIs "remains controversial", although phase 3 trials showed non-inferiority to lansoprazole.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 38345252 | 2024 | Systematic review / network meta-analysis | Am J Gastroenterol | Compares P-CABs with PPIs for healing Los Angeles grade C/D esophagitis (efficacy and safety) |
| 28988197 | 2018 | RCT | Gut | Vonoprazan vs lansoprazole for preventing NSAID-associated ulcer recurrence; non-inferiority design with extension study on long-term safety |
| 28267236 | 2017 | RCT | Dig Endosc | Healing effect of vonoprazan on artificial gastric ulcers after endoscopic submucosal dissection |
| 39156336 | 2024 | Review | Cureus | Efficacy and safety of vonoprazan in GERD, peptic ulcer disease and H. pylori infection |
| 36660052 | 2023 | Review / guideline | JGH Open | Management of H. pylori infection, a leading cause of peptic ulcer disease |
| 32998241 | 2020 | Review | Pharmaceuticals | Potential benefits of vonoprazan in H. pylori therapy |
| 37066678 | 2023 | PK/PD study | Aliment Pharmacol Ther | Translational PK/PD approach supporting vonoprazan dosing for erosive oesophagitis and H. pylori |
| 42084149 | 2026 | Narrative review | Pol Arch Intern Med | P-CABs for erosive reflux disease and stress ulcer prophylaxis |
| 26369775 | 2016 | Review (PK/PD) | Clin Pharmacokinet | First-in-class P-CAB; approved in Japan for gastroduodenal ulcer and for secondary prevention of NSAID/aspirin ulcers |
Other retrieved papers are narrative reviews of H. pylori resistance and eradication, or preclinical plant-extract studies, and are not directly relevant.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15444P | VOCINTI Film-Coated Tablet 20mg | Tablet, film coated | Not specified in the available data |
| SIN15445P | VOCINTI Film-Coated Tablet 10mg | Tablet, film coated | Not specified in the available data |
Both licences are valid single-ingredient products from Takeda Pharmaceutical Company Limited (Hikari Plant), for oral use.
Safety Considerations
- Drug Interactions: The interaction query completed, but the only record is pharmacological target information (vonoprazan acting on ATP4A, the gastric proton pump), not a drug-drug interaction.
- Long-term use: Published case reports describe gastric mucosal changes, mucosal redness, white globe appearance lesions, and severe rebound acid hypersecretion after long-term use (e.g., PMID 39712905). These are single cases but are relevant to monitoring.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Active peptic ulcer disease overlaps with vonoprazan's established gastric and duodenal ulcer use, and phase 3 RCTs and meta-analyses support it. However, no trials are registered for this indication, and mechanism and safety data are incomplete.
To proceed, the following is needed:
- Singapore package insert warnings and contraindications from HSA (currently a blocking gap for safety screening)
- Approved indication wording for the two Singapore licences
- Detailed mechanism of action data from DrugBank
- A plan for monitoring long-term use (gastric mucosal changes, rebound acid hypersecretion)
Other Predictions Reviewed
Lower-ranked predictions do not currently support further action:
| Predicted Indication | Score | Evidence | Assessment | |------|------|------|------| | Peptic ulcer perforation | 99.97% | Guidelines and a general ulcer meta-analysis only (indirect) | Hold | | Gastrojejunal ulcer | 99.97% | Extrapolated from peptic ulcer, GERD and H. pylori literature | Research question | | Hiatus hernia | 99.88% | Observational GERD studies; vonoprazan treats reflux symptoms, not the hernia | Research question | | Hemorrhagic duodenitis | 99.74% | Indirect, from duodenal ulcer RCTs | Research question | | Achlorhydria | 99.86% | No evidence; mechanistically contradictory, since the drug further suppresses acid | Hold | | Gastric dilatation, cascade stomach, pylorospasm, Dieulafoy lesion | 99.85% | No supporting evidence; likely knowledge-graph artifacts | Hold |
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.