Chlorpheniramine
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Chlorpheniramine: From Allergic Rhinitis to Allergic Urticaria
One-Sentence Summary
Chlorpheniramine is a first-generation H1 antihistamine, originally used for allergic rhinitis, the common cold, allergic conjunctivitis and urticaria. The TxGNN model predicts it may be effective for allergic urticaria, but this is essentially an on-label or near on-label use. No clinical trials are registered for this indication, and the literature consists mostly of general antihistamine reviews and case reports (about 20 publications).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Allergic rhinitis, vasomotor rhinitis, pharyngitis, common cold, atopic/vernal/papillary conjunctivitis, urticaria, angioedema, familial dermatographia (the licence records list no indication text) |
| Predicted New Indication | Allergic urticaria |
| TxGNN Prediction Score | 99.76% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 20 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data are not available in the data compiled for this report. Based on known pharmacology, chlorpheniramine is an H1-receptor antagonist. It blocks the effects of histamine on peripheral tissues, which reduces itching, swelling and wheal formation.
Allergic urticaria is a histamine-mediated skin condition, and H1 antihistamines are the standard first-line treatment. Urticaria and angioedema are already among the drug's recognised uses, so the mechanistic fit is strong. However, this is not a true repurposing case. The prediction mostly restates an existing use rather than revealing a new one.
The supporting literature is mostly reviews of H1 antihistamines in general, not chlorpheniramine-specific trials. For this reason the evidence is rated L4 (mechanism and class-level support), not higher.
Clinical Trial Evidence
Currently no related clinical trials registered for allergic urticaria.
For context, the related prediction "rhinitis" (rank 10) has four registered trials, none of which produced usable chlorpheniramine data:
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT04790487 | Phase 2/3 | Withdrawn | 0 | Placebo-controlled trial of chlorpheniramine nasal spray in acute or chronic rhinitis; no participants enrolled |
| NCT02722083 | Phase 2 | Terminated | 1 | Pilot on onset of action of an antihistamine in an allergen chamber; no usable results |
| NCT02082054 | Phase 2 | Unknown | 125 | Atropine doses combined with pseudoephedrine and chlorpheniramine in seasonal allergic rhinitis |
| NCT03879772 | Phase 3 | Completed | 679 | Mometasone nasal spray dose-ranging in children; a different drug, so no direct chlorpheniramine evidence |
Literature Evidence
Publications most relevant to urticaria (the cold urticaria study, PMID 334082, comes from the related rank 4 prediction):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 334082 | 1977 | RCT (double-blind, small) | Arch Dermatol | Chlorpheniramine, cyproheptadine and placebo compared in 8 patients with primary acquired cold urticaria |
| 35652393 | 2024 | Review | Curr Rev Clin Exp Pharmacol | Comprehensive review of chlorpheniramine uses, including chronic urticaria |
| 11702618 | 2001 | Review | Am J Clin Dermatol | Evidence-based evaluation of antihistamines, the mainstay of urticaria treatment |
| 1683523 | 1991 | Review | Ann Allergy | Comparative efficacy of H1 antihistamines |
| 7528133 | 1994 | Review | Drugs | Loratadine was as effective as chlorpheniramine and other antihistamines in allergic disorders |
| 2873823 | 1986 | Cohort | Asian Pac J Allergy Immunol | Urticaria in 142 Thai children, describing causes and clinical features |
| 31852144 | 2019 | Case report and database review | Medicine | Two cases of chlorpheniramine-induced anaphylaxis plus pharmacovigilance review |
| 26240795 | 2015 | Case report | Asia Pac Allergy | Chlorpheniramine-induced anaphylaxis diagnosed by basophil activation test |
| 21217928 | 2011 | Case report | Allergy Asthma Immunol Res | Chlorpheniramine hypersensitivity in a patient with aspirin intolerance |
Singapore Market Information
Twenty single-ingredient licences are valid. Five main examples:
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN10511P | AXCEL Chlorpheniramine Tablets 4 mg | Tablet | Not stated |
| SIN03348P | Allersin Syrup 4 mg/5 ml | Syrup | Not stated |
| SIN10028P | Pirimat Injection 10 mg/ml | Injection | Not stated |
| SIN07343P | Flucur Nebuliser | Spray | Not stated |
| SIN05255P | Fenfedrin Capsule | Capsule | Not stated |
Available forms include tablets, capsules, syrups, a suspension, sprays and an injection.
Safety Considerations
- Contraindications flagged in the knowledge graph (not label text): hypertension, liver disease and failure, kidney disease, epilepsy, chronic obstructive pulmonary disease, peptic ulcer and gastric ulcer, benign prostatic hyperplasia, diabetes mellitus, hypothyroidism, psychotic and other mental disorders, inflammatory bowel disease, pancreatitis, thrombocytopenia, and others. These should be verified against the package insert.
- Drug Interactions: 100 interactions were found. The two Major ones are potassium chloride and potassium citrate. Moderate interactions include anticholinergics (atropine, dicyclomine, glycopyrronium, methscopolamine, mepenzolate), opioids (morphine, opium), bupropion, metoclopramide, loperamide, dronabinol and nabilone.
- Hypersensitivity: several case reports describe anaphylaxis or urticaria caused by chlorpheniramine itself (PMIDs 26240795, 31852144, 21217928).
Please refer to the package insert for the complete warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction is mechanistically sound, but allergic urticaria is already close to an existing use, so it adds little repurposing value. There are no registered trials, and the literature is mostly general antihistamine reviews, with only one small 1977 chlorpheniramine study in a related condition (cold urticaria).
To proceed, the following is needed:
- Package insert warnings and contraindications from the HSA website
- Detailed mechanism of action data from DrugBank
- Chlorpheniramine-specific clinical evidence in urticaria, or confirmation that the current labelled urticaria indication already covers it
- Review of the knowledge-graph contraindications and the Major potassium interactions for the target population
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.