Ranitidine
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Ranitidine: From Gastric Ulcer and Reflux Disease to Active Peptic Ulcer Disease
One-Sentence Summary
Ranitidine is a histamine H2-receptor blocker, originally used to treat gastric and duodenal ulcers, gastroesophageal reflux disease and related acid-driven conditions. The TxGNN model predicts it may be effective for active peptic ulcer disease, but this is essentially one of its original indications rather than a true new use. No clinical trials are directly linked to this prediction, and 20 publications were compiled, mostly drug reviews and comparisons with other acid suppressants. The related prediction "peptic ulcer disease" has 5 linked trials (none of which tests ranitidine as the main drug) and 20 publications.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Gastric ulcer, gastroesophageal reflux disease, esophagitis, dyspepsia, duodenal ulcer, Zollinger-Ellison syndrome (from the TxGNN knowledge graph; Singapore licence indication text is blank) |
| Predicted New Indication | Active peptic ulcer disease |
| TxGNN Prediction Score | 99.89% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 5 |
| 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, ranitidine is a competitive H2-receptor antagonist. It reduces basal and stimulated gastric acid and pepsin secretion, and acid suppression is a recognised basis for ulcer healing.
Active peptic ulcer disease overlaps almost entirely with ranitidine's original indications (gastric ulcer, duodenal ulcer). The model's high score therefore mostly reflects that overlap, so this is not a genuine repurposing candidate. Reviewed literature shows ranitidine heals duodenal and gastric ulcers at rates comparable to cimetidine, though PPIs heal faster in head-to-head comparisons.
Other predictions in the list are weaker. Peptic ulcer perforation, gastrojejunal ulcer, duodenogastric reflux and duodenal obstruction have only indirect evidence. Gastroduodenitis has clinical-level evidence (L3), largely overlapping the original indications. Mastocytosis variants and abnormal glucagon secretion rest on model prediction alone (L5).
Clinical Trial Evidence
No clinical trials are linked to "active peptic ulcer disease". The table below shows trials linked to the closely related prediction "peptic ulcer disease".
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00401752 | Phase 3 | Completed | 397 | Esomeprazole 20 mg daily vs ranitidine 150 mg twice daily for NSAID-associated gastric ulcer; ranitidine appears to be the comparator (8-week, double-blind) |
| NCT00633672 | Phase 3 | Completed | 400 | Esomeprazole 40 mg or 20 mg vs ranitidine 150 mg twice daily for NSAID-associated gastric ulcer healing |
| NCT00633412 | Phase 3 | Completed | 400 | US-only version of the same esomeprazole vs ranitidine design |
| NCT01538797 | Phase 1 | Completed | 22 | YF476 vs placebo and ranitidine on 24-hour gastric pH in healthy volunteers |
| NCT00247130 | Phase 4 | Withdrawn | 0 | IV omeprazole vs IV ranitidine after endoscopic treatment of bleeding ulcer; no data |
These trials are mainly about other drugs (esomeprazole, omeprazole, YF476), with ranitidine as the comparator, so they give only indirect support.
Literature Evidence
Publications linked to "active peptic ulcer disease":
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 6317325 | 1983 | Review | Drug Intell Clin Pharm | Ranitidine is 4-10 times more potent than cimetidine in inhibiting acid secretion and similarly effective and tolerated in duodenal ulcer |
| 2905237 | 1988 | Review | Drugs | Prostaglandins and H2-receptor antagonists in peptic ulcer pathogenesis and treatment |
| 2905640 | 1988 | Review | Drugs | Nizatidine (another H2 blocker) in peptic ulcer disease |
| 9198292 | 1997 | Review | Zhonghua Yi Xue Za Zhi | Clarithromycin combination therapy for H. pylori eradication in peptic ulcer disease |
| 3909374 | 1985 | Clinical study | Scand J Gastroenterol | Ranitidine 300 mg/day: 4-week healing 91% in duodenal ulcer, 81% gastric corporeal ulcer, 68% prepyloric ulcer; maintenance therapy studied |
| 6317740 | 1983 | Comparative study | J Clin Gastroenterol | Ranitidine is 6-8 times more potent than cimetidine in inhibiting gastric secretion |
Literature for the related prediction "peptic ulcer disease" also includes a randomized trial of ranitidine for NSAID-related dyspepsia in arthritis patients (8894357, 1996, Clin Rheumatol) and reviews of ranitidine in peptic ulcer disease (6128216, 1982; 2667937, 1989, both Drugs).
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN11750P | ACILOC 150 TABLET 150 mg | Film-coated tablet | Not stated |
| SIN10248P | ZYNOL-150 TABLET 150 mg | Film-coated tablet | Not stated |
| SIN05429P | APO-RANITIDINE TABLET 150 mg | Film-coated tablet | Not stated |
| SIN10081P | GASTRIL INJECTION 50 mg/2 ml | Injection | Not stated |
| SIN11751P | ACILOC 300 TABLET 300 mg | Film-coated tablet | Not stated |
All five licences are valid single-ingredient products, covering oral and injectable routes.
Safety Considerations
- Disease associations from the knowledge graph (not label text): Contraindication links were found for porphyria (including inherited porphyria and porphyrin metabolism disease), kidney disease, liver disease, gallbladder disease, and gastric cancer or neoplasm (including diffuse gastric adenocarcinoma, linitis plastica and gastric carcinoma). Treatment may mask symptoms of gastric malignancy, so these should be checked against the package insert.
- Drug Interactions: 100 interactions were recorded. Among those listed, atazanavir is classed Major. Moderate interactions include acalabrutinib, bosutinib, brigatinib, ceritinib, aminophylline, several cephalosporins (cefditoren, cefpodoxime, cefuroxime), bacampicillin, and sulfonylureas (acetohexamide, chlorpropamide). Many of these likely involve reduced absorption from raised gastric pH. Minor interactions include antacids, acetaminophen and alendronic acid.
- Market issue: The compiled review notes that ranitidine was withdrawn from many markets over NDMA contamination, which limits any new development.
Package insert warnings and contraindications were not available in the compiled data; please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: Active peptic ulcer disease is effectively an original indication, so it is not a true repurposing opportunity. Evidence is limited to reviews and indirect trials where ranitidine is a comparator. PPIs are generally superior and are the standard of care, and NDMA-related withdrawals further limit new use.
To proceed, the following is needed:
- Package insert warnings and contraindications from HSA (a blocking gap for safety screening)
- Mechanism of action data from DrugBank
- Indication text for the Singapore licences
- Current NDMA/quality status of ranitidine products in Singapore
- Ranitidine-specific randomized trial evidence for any genuinely new indication, since the remaining predictions (gastroduodenitis, mastocytosis variants, abnormal glucagon secretion) have only indirect or model-only support
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.