Rupatadine
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Rupatadine: From Allergic Rhinitis and Urticaria to Cold Urticaria
One-Sentence Summary
Rupatadine is a second-generation antihistamine that also blocks platelet-activating factor (PAF). It was originally used for allergic rhinitis, vasomotor rhinitis, urticaria and angioedema. The TxGNN model predicts it may be effective for cold urticaria, with 1 completed Phase 2 clinical trial and 7 publications currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Allergic rhinitis, vasomotor rhinitis, urticaria, angioedema (the Singapore licence records contain no approved indication text) |
| Predicted New Indication | Cold urticaria |
| TxGNN Prediction Score | 96.97% |
| Evidence Level | L2 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Rupatadine acts on two targets: the histamine H1 receptor and the PAF receptor. It competitively inhibits PAF-induced platelet aggregation, with an IC50 of 680 nM in human platelet-rich plasma. Detailed mechanism-of-action text is not available in the data compiled for this report, but the pharmacology data confirm these two targets.
Cold urticaria is an inducible form of urticaria. Cold exposure triggers mast cell degranulation, releasing histamine and possibly PAF, which produce wheals and itch. Blocking H1 and PAF receptors can plausibly reduce these responses. Rupatadine is already used for urticaria, so this prediction extends an existing use to a specific subtype rather than opening a completely new therapeutic area.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01605487 | Phase 2 | Completed | 24 | Double-blind, three-way cross-over, placebo-controlled study of rupatadine 20 mg and 40 mg in cold contact urticaria. Symptom development was assessed with a standardised temperature provocation device (TempTest). |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 26038847 | 2016 | RCT | Acta Derm Venereol | Randomised, double-blind, placebo-controlled crossover study. Rupatadine 20 mg and 40 mg were effective in reducing chronic cold urticaria symptoms. |
| 20143651 | 2010 | RCT | Ann Allergy Asthma Immunol | Rupatadine's effects on symptom control, stimulation time and temperature thresholds in acquired cold urticaria. |
| 19392988 | 2009 | Clinical study | Allergy | Treatment of acquired cold urticaria with rupatadine. |
| 24977664 | 2015 | Prospective study | Acta Derm Venereol | One-year observational study of temperature thresholds for assessing the clinical course of acquired cold contact urticaria (19 patients). |
| 23806068 | 2013 | Review | Expert Opin Pharmacother | Rupatadine is a dual PAF and histamine antagonist with rapid onset, once-daily dosing and good tolerability. |
| 25491409 | 2015 | Review | Allergy | Update on rupatadine's broader anti-inflammatory role, including PAF antagonism, in allergic disorders. |
| 41424665 | 2025 | Case series | Drugs Context | Real-world off-label use of rupatadine in allergic and skin disorders. |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN14868P | RUPAFIN ORAL SOLUTION 1mg/ml | Solution | Not stated in the licence record |
| SIN14087P | Rupafin Tablet 10mg | Tablet | Not stated in the licence record |
Safety Considerations
- Pharmacological targets: Rupatadine acts on the H1 receptor (HRH1) and the PAF receptor (PTAFR). No drug-drug interactions with specific named drugs were found in the data compiled for this report.
- The cold urticaria trials tested 20 mg and 40 mg, which exceed the 10 mg tablet strength registered in Singapore. Safety at these higher doses should be checked against the package insert.
Please refer to the package insert for other safety information, including warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: A completed placebo-controlled Phase 2 crossover trial and two randomised studies support rupatadine in cold urticaria, and the mechanism is plausible and consistent with its approved urticaria use. The evidence comes from small studies, and up-dosing goes beyond the registered 10 mg strength.
To proceed, the following is needed:
- Review of the HSA package insert for warnings, contraindications and approved indication wording
- Confirmation of the dose, including up-dosing, and the target population against local labelling
- Confirmation of the full detailed mechanism of action
- Larger confirmatory trials, ideally in a Singapore or Asian population
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.