Ranitidine
| Evidence Level: L1 | Predicted Indications: 6 |
Table of Contents
Ranitidine: Peptic ulcer perforation
One-Sentence Summary
Ranitidine is a histamine H2-receptor antagonist, originally used for gastric and duodenal ulcers, gastro-oesophageal reflux disease and related acid-hypersecretion conditions. For this top-ranked prediction there are no registered clinical trials and 20 publications (mostly reviews).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Peptic ulcer perforation |
| TxGNN Prediction Score | 0.9988 |
| Evidence Level | L1 (as assigned in the data compiled for this report; see note under Clinical Trial Evidence) |
| 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 | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. From established pharmacology, ranitidine is a histamine H2-receptor antagonist. It reduces gastric acid secretion, and acid suppression supports ulcer healing. The literature describes it as four to ten times more potent than cimetidine in inhibiting stimulated acid secretion.
Other predictions are weaker. These include gastrojejunal ulcer, peptic ulcer perforation, duodenogastric reflux, duodenal obstruction, gastroduodenitis, mastocytosis variants and abnormal glucagon secretion. They rest on indirect evidence or none, and are not the focus of this report.
Clinical Trial Evidence
Currently no related clinical trials are registered for “active peptic ulcer disease”.
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT00633672 | Phase 3 | Completed | 400 | Esomeprazole 40 mg or 20 mg daily vs ranitidine 150 mg twice daily for healing NSAID-associated gastric ulcers |
| NCT00633412 | Phase 3 | Completed | 400 | US-only parallel study of the same esomeprazole vs ranitidine comparison |
| NCT00401752 | Phase 3 | Completed | 397 | 8-week double-blind comparison of esomeprazole 20 mg daily vs ranitidine 150 mg twice daily in NSAID-associated gastric ulcer |
| NCT00247130 | Phase 4 | Withdrawn | 0 | IV omeprazole vs IV ranitidine after endoscopic treatment of bleeding ulcer; no data |
| NCT01538797 | Phase 1 | Completed | 22 | YF476 vs placebo and ranitidine on 24-hour gastric pH in healthy volunteers; pharmacodynamic only |
Note: In the Phase 3 trials ranitidine appears to be the comparator, not the test drug. The L1 rating is based on the existence of these trials, so it should be read cautiously. No ANZCTR identifiers were found in the data.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 9753259 | 1998 | RCT | Dig Dis Sci | Double-blind study of 472 duodenal ulcer patients: omeprazole vs ranitidine 150 mg for maintenance of remission |
| 6128216 | 1982 | Review | Drugs | Ranitidine 150 mg twice daily was an effective alternative to cimetidine for healing duodenal and gastric ulcers (comparator also covered in the related ulcer predictions) |
| 2667937 | 1989 | Review | Drugs | Updated review: ranitidine 300 mg daily at least as effective as cimetidine in ulcer healing |
| 6317325 | 1983 | Review | Drug Intell Clin Pharm | Ranitidine is 4 to 10 times more potent than cimetidine, similarly effective and well tolerated |
| 6317740 | 1983 | Not classified | J Clin Gastroenterol | Comparative pharmacodynamics and pharmacokinetics of cimetidine and ranitidine |
| 3909374 | 1985 | Clinical study | Scand J Gastroenterol | Ranitidine 300 mg daily: 4-week healing 91% (duodenal), 68% (prepyloric), 81% (gastric corporeal); maintenance vs placebo studied |
| 2905237 | 1988 | Review | Drugs | Prostaglandins, H2 antagonists and peptic ulcer pathophysiology |
| 2878343 | 1986 | Not classified | Med Toxicol | Adverse reactions and interactions with H2-receptor antagonists; low toxicity |
| 9506245 | 1998 | Review | Drugs | Rabeprazole (a PPI) compared with H2 blockers in ulcer trials |
| 3104657 | 1986 | Not classified | Klin Wochenschr | Rioprostil vs ranitidine in duodenal ulcer healing |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 1977C | Zantac 300 | Tablet 300 mg (as hydrochloride) | Not available in the data compiled |
Safety Considerations
Contraindication-related disease associations (from the TxGNN knowledge graph, not from label text): inherited porphyria and other porphyrin metabolism disorders, kidney disease, pyoureter, liver disease, gallbladder disease, and gastric cancer (including gastric neoplasm, diffuse gastric adenocarcinoma, linitis plastica and gastric carcinoma). These should be checked against the Product Information.
Drug Interactions: 100 interactions were identified (DDInter). Examples from the first records:
- Major: atazanavir
- Moderate: acalabrutinib, acetohexamide, aminophylline, bacampicillin, bosutinib, brigatinib, cefditoren, cefpodoxime, cefuroxime, ceritinib, chlorpropamide
- Minor: acetaminophen, alendronic acid, aluminium hydroxide, atracurium, axitinib, calcium carbonate, cisapride, cisatracurium
Many of these reflect reduced absorption of drugs that need gastric acid. Please refer to the TGA-approved Product Information (PI) for warnings and full interaction guidance.
Supply and quality: The data note that ranitidine was withdrawn from many markets in 2019-2020 because of NDMA contamination. The “Marketed” status should therefore be verified locally.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: The prediction is mainly on-label use (acid-related ulcer disease), supported by decades of literature and Phase 3 trials where ranitidine served as comparator. It is not a novel repurposing finding. Newer acid suppressants (PPIs) are generally preferred, and market availability is uncertain.
To proceed, the following is needed:
- Verify the current ARTG status and supply of ranitidine in Australia (NDMA-related withdrawals)
- Obtain the approved indication text and PI warnings and contraindications for ARTG 1977C
- Confirm ranitidine’s role (comparator vs test drug) in the Phase 3 trials
- Compare against PPIs and other H2 blockers for place in therapy
- Obtain mechanism of action data from DrugBank to complete the mechanistic analysis
Other predictions: gastrojejunal ulcer and gastroduodenitis (L4, research questions) and peptic ulcer perforation, duodenogastric reflux, duodenal obstruction, mastocytosis variants and abnormal glucagon secretion (Hold) lack direct supporting evidence.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.