Ranitidine
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Using the v5 report template to produce the requested evaluation.
Ranitidine: From Peptic Ulcer Disease to Active Peptic Ulcer Disease
One-Sentence Summary
Ranitidine is a histamine H2-receptor antagonist historically used to treat peptic ulcer disease and related acid-related gastrointestinal conditions. The TxGNN model’s top prediction for this drug is Active Peptic Ulcer Disease — a condition that is essentially identical to ranitidine’s own classic, long-established use rather than a genuinely novel indication — supported by 1 clinical trial and 19 publications, most of which pre-date the drug’s global market withdrawal.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Peptic ulcer disease (classic H2-antagonist indication; not currently held on any UK licence) |
| Predicted New Indication | Active Peptic Ulcer Disease |
| TxGNN Prediction Score | 99.89% |
| Evidence Level | L2 |
| UK Market Status | Not marketed |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed DrugBank mechanism-of-action data is not available in this evidence pack (flagged as a High-severity data gap). However, the underlying literature is unambiguous: ranitidine is a selective, competitive histamine H2-receptor antagonist that inhibits basal and stimulated gastric acid secretion by blocking H2 receptors on gastric parietal cells. This is a well-characterised, decades-old pharmacological mechanism.
The TxGNN model’s top-ranked prediction, “active peptic ulcer disease,” is mechanistically and clinically almost indistinguishable from ranitidine’s own historical, approved indication (“peptic ulcer disease,” also captured separately at rank 7 with the highest evidence level, L1, in this pack). In other words, the model has largely re-identified the drug’s existing, well-established use rather than surfaced a genuinely new repurposing opportunity. This is a useful internal-consistency check on the model, but it should not be read as evidence of a novel therapeutic application.
It is important to note that ranitidine products were withdrawn from markets worldwide, including the UK, from 2019–2020 following detection of N-nitrosodimethylamine (NDMA), a probable human carcinogen, in various formulations. This is consistent with the “Not marketed” status and zero marketing authorisations recorded in this evidence pack, and it is the dominant factor governing any repurposing decision for this molecule — regardless of how strong the underlying acid-suppression pharmacology is.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT00930670 | Phase 4 | Completed | 320 | Evaluated the effect of various PPIs (and statins) on clopidogrel antiplatelet activity in PCI patients; ranitidine/H2-antagonist relevance is indirect (relevance grade C — not a direct efficacy trial for active peptic ulcer disease). |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 3909374 | 1985 | RCT | Scand J Gastroenterol | Ranitidine 300 mg/day healed 91% of duodenal ulcers, 68% of prepyloric ulcers, 81% of gastric corporeal ulcers at 4 weeks; maintenance therapy reduced relapse vs placebo. |
| 2877570 | 1986 | RCT | Am J Med | Multicentre, randomised, double-blind trial (1,031 patients, 19 countries) comparing famotidine with ranitidine for active duodenal ulcer healing. |
| 2491360 | 1989 | RCT | J Gastroenterol Hepatol | Randomised double-blind study (270 patients) comparing omeprazole doses with ranitidine 150 mg bid for duodenal ulcer healing and relapse, with weekly endoscopic assessment. |
| 2092029 | 1990 | RCT | J Assoc Physicians India | Double-blind randomised trial comparing famotidine 40 mg with ranitidine 300 mg nocte in endoscopically diagnosed peptic ulcer. |
| 1863945 | 1991 | RCT | Clin Ther | Multicentre study (160 patients) comparing famotidine and ranitidine for active duodenal ulcer healing and 6-month maintenance, including NSAID/aspirin-related ulcers. |
| 6317325 | 1983 | Review | Drug Intell Clin Pharm | Overview confirming ranitidine’s approval for active duodenal ulcer and gastric hypersecretory conditions; 4–10x more potent than cimetidine. |
| 1976583 | 1990 | Review | Hepatogastroenterology | Reviews acid suppression as the central mechanism underlying peptic ulcer healing across H2-antagonists. |
| 12749277 | 2003 | Controlled Study | Hepatogastroenterology | Prospective controlled study of ranitidine plus ecabet vs ranitidine alone for prevention of peptic ulcer relapse, independent of H. pylori eradication. |
| 34986535 | 2021 | Preclinical (animal model) | J Zhejiang Univ Med Sci | Investigated a herbal extract’s protective effect against ethanol-induced gastric ulcer; ranitidine-class mechanism referenced as comparator context. |
UK Market Information
Ranitidine currently holds no marketing authorisations in the UK (0 licences recorded). This reflects the global withdrawal of ranitidine-containing products following the 2019–2020 discovery of NDMA impurities, and is consistent with the “Not marketed” status in this evidence pack. No dosage forms or licensed products are available to reference.
Safety Considerations
No structured safety data (key warnings, contraindications, or drug–drug interactions) is available in this evidence pack — the TFDA/MHRA labelling review (DG001) is flagged as a Blocking data gap.
- Historical safety signal: Ranitidine products were withdrawn worldwide, including in the UK, in 2019–2020 due to detection of NDMA, a probable human carcinogen, in some formulations. Any repurposing evaluation must account for this before further pharmacological assessment.
Please refer to the SmPC and BNF for further safety information, and report suspected adverse reactions via the Yellow Card Scheme.
Conclusion and Next Steps
Decision: Hold
Rationale: The top-ranked prediction largely reproduces ranitidine’s own historical indication rather than identifying a genuinely new therapeutic use, and the drug currently holds zero UK marketing authorisations following its global withdrawal over NDMA contamination concerns. Without a resolved product/manufacturing safety issue and current labelling data, this candidate cannot proceed past initial safety screening (S1).
To proceed, the following is needed:
- MHRA/current UK product labelling, warnings and contraindications (Blocking data gap, DG001)
- Confirmed mechanism-of-action documentation from DrugBank (High-severity data gap, DG002)
- Resolution or reassessment of the NDMA impurity issue for any reformulated or purified product before repurposing can be meaningfully considered
- Reassessment of whether “active peptic ulcer disease” represents a distinct clinical opportunity from ranitidine’s known original indication, or should be deprioritised as a non-novel prediction
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.