Ranitidine
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Ranitidine: From Gastric Ulcer to Active Peptic Ulcer Disease
One-Sentence Summary
Ranitidine is an H2-receptor antagonist originally used to treat gastric and duodenal ulcers, reflux disease and acid hypersecretory conditions. The TxGNN model predicts it may be effective for active peptic ulcer disease, but this is essentially the same as its original indication rather than a true new use. There are no registered clinical trials for this exact term and 20 publications (mostly reviews and comparator papers), so the evidence is only indirect.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Gastric ulcer, gastroesophageal reflux disease, esophagitis, duodenal ulcer, Zollinger-Ellison syndrome (label indication text is not available; taken from the knowledge graph) |
| Predicted New Indication | Active peptic ulcer disease |
| TxGNN Prediction Score | 99.89% |
| Evidence Level | L4 |
| US Market Status | Cancelled only (all licences cancelled) |
| Number of NDAs | 9 (all cancelled 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 pharmacology, ranitidine is a competitive histamine H2-receptor antagonist. It lowers basal and stimulated gastric acid secretion, which is the basis of ulcer healing.
Active peptic ulcer disease overlaps almost entirely with ranitidine’s original indications (gastric and duodenal ulcer). The high TxGNN score therefore mostly reflects this overlap, and the prediction is not a genuine repurposing opportunity.
Other predicted indications are weaker still. Perforation, duodenal obstruction and duodenogastric reflux are mainly surgical or non-acid problems, and ranitidine could help only with an underlying ulcer. Mastocytosis variants are plausible only for symptomatic control of histamine-driven gastric hypersecretion. For abnormality of glucagon secretion, no mechanistic link is established.
Clinical Trial Evidence
No registered trials for “active peptic ulcer disease” were found. The closest term, “peptic ulcer disease” (a separate prediction, score 99.58%), returned five trials. None of them tests ranitidine as the intervention under study.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00633672 | Phase 3 | Completed | 400 | Esomeprazole 40 mg/20 mg vs ranitidine 150 mg twice daily for healing NSAID-associated gastric ulcers |
| NCT00633412 | Phase 3 | Completed | 400 | Same design as above, US-only subjects |
| NCT00401752 | Phase 3 | Completed | 397 | Esomeprazole 20 mg vs ranitidine 150 mg twice daily over 8 weeks in NSAID-associated gastric ulcer |
| NCT00247130 | Phase 4 | Withdrawn | 0 | IV omeprazole vs IV ranitidine to maintain haemostasis after endoscopic treatment of bleeding ulcer; never enrolled |
| NCT01538797 | Phase 1 | Completed | 22 | YF476 vs placebo and ranitidine on 24-hour gastric pH in healthy volunteers |
Ranitidine appears as the comparator in the trial titles, but these studies were designed to test other drugs, and the relevance review graded all five as low.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 6317325 | 1983 | Review | Drug Intell Clin Pharm | Ranitidine is 4-10 times more potent than cimetidine, similarly effective and well tolerated in duodenal ulcer and hypersecretory states |
| 3909374 | 1985 | Clinical study | Scand J Gastroenterol | Ranitidine 300 mg/day: 4-week healing 91% (duodenal), 68% (prepyloric), 81% (gastric corporeal); maintenance therapy studied for relapse prevention |
| 6317740 | 1983 | Review | J Clin Gastroenterol | Comparison of ranitidine and cimetidine pharmacodynamics and pharmacokinetics |
| 2878343 | 1986 | Review | Med Toxicol | Adverse reactions and interactions of H2 antagonists; low toxicity overall |
| 2905237 | 1988 | Review | Drugs | Role of prostaglandins and H2 antagonists in peptic ulcer disease |
| 9506245 | 1998 | Review | Drugs | Rabeprazole (a PPI) review; comparative trials against H2 blockers |
| 2905640 | 1988 | Review | Drugs | Nizatidine review in peptic ulcer disease |
| 3104657 | 1986 | Clinical study | Klin Wochenschr | Nocturnal rioprostil vs ranitidine in duodenal ulcer healing |
| 11166000 | 2001 | Review | Am J Med | Omeprazole was superior to an ineffective dose of ranitidine for NSAID ulcer prevention (ASTRONAUT) |
| 1976583 | 1990 | Review | Hepato-gastroenterology | Acid suppression and ulcer healing |
These are older drug reviews and comparator papers. None is a modern ranitidine-focused randomised trial for this indication.
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ANDA077824 | Ranitidine (Amneal) | Tablet | Not available (cancelled) |
| ANDA211289 | Ranitidine (Rising Pharma) | Tablet | Not available (cancelled) |
| ANDA078192 | Ranitidine (Dr. Reddy’s) | Coated tablet | Not available (cancelled) |
| ANDA210243 | Ranitidine (Granules India) | Tablet | Not available (cancelled) |
| ANDA209859 | Ranitidine (Ajanta Pharma) | Capsule | Not available (cancelled) |
Nine licences in total are on record, and all are cancelled. The remaining four are Acid Reducer (WinCo Foods, film-coated tablet), Ranitidine syrup (Pharmaceutical Associates), and two further Dr. Reddy’s products (capsule and tablet). The market withdrawal is linked to NDMA contamination concerns.
Safety Considerations
- Contraindications (from the knowledge graph, not label text): inherited porphyria and other porphyrin metabolism disorders, kidney disease, liver disease, gallbladder disease, pyoureter, and gastric cancer or neoplasm (several gastric cancer subtypes are listed).
- Drug Interactions: 100 interactions were found; the first 20 retrieved include:
- Major: atazanavir.
- Moderate: acalabrutinib, acetohexamide, aminophylline, bacampicillin, bosutinib, brigatinib, cefditoren, cefpodoxime, cefuroxime, ceritinib, chlorpropamide. Many of these reflect reduced absorption when gastric acid is suppressed.
- Minor: acetaminophen, alendronic acid, aluminium hydroxide, atracurium, axitinib, calcium carbonate, cisapride, cisatracurium.
- Please refer to the package insert for full warnings and contraindications, as label text was not available. NDMA contamination, which led to the market withdrawal, is also a key concern.
Conclusion and Next Steps
Decision: Hold
Rationale:
- Active peptic ulcer disease is not a new indication for ranitidine, so the prediction offers no repurposing value. All US licences are cancelled, and no trial tests ranitidine for this use. Evidence is L4: only indirect, mostly historical literature.
To proceed, the following is needed:
- Mechanism of action data and the FDA label warnings and contraindications
- Resolution of the NDMA contamination issue and the market status
- A clear rationale for choosing ranitidine over PPIs or other H2 blockers still on the market (e.g., famotidine)
- Only if development is pursued: a genuinely distinct indication with direct supporting evidence (the mastocytosis variants are plausible but currently have no data)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.