Chlorpheniramine
| Evidence Level: L3 | Predicted Indications: 4 |
Table of Contents
Chlorpheniramine: From Established H1-Antihistamine Use to Allergic Urticaria
One-Sentence Summary
Chlorpheniramine is a first-generation H1 antihistamine, widely marketed in the US for allergic conditions. The TxGNN model predicts it may be effective for allergic urticaria. 3 clinical trials and 19 publications were retrieved, but none is a trial of chlorpheniramine in urticaria, so this is likely an established use rather than true repurposing.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the source data (approved indication text is empty for all listed products) |
| Predicted New Indication | Allergic urticaria |
| TxGNN Prediction Score | 99.76% |
| Evidence Level | L3 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the source record. Chlorpheniramine (chlorphenamine) is a potent alkylamine first-generation H1-receptor antagonist, in use since the 1950s. It is commonly used for allergic conditions and over-the-counter cough and cold products.
In allergic urticaria, histamine released from mast cells drives the wheal and flare response. Blocking the H1 receptor therefore acts directly on the disease mechanism. H1 antihistamines are the mainstay of urticaria treatment, and a 2024 review lists chronic urticaria among chlorpheniramine’s documented uses.
The missing original indication and MOA look like a source data gap rather than evidence of a novel use. The prediction is best read as confirming an existing, mechanistically direct use. Current practice favors second-generation antihistamines, so chlorpheniramine’s value here is largely as a low-cost, long-established option.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01293201 | Phase 3 | Completed | 290 | Placebo-controlled trial of STAHIST (pseudoephedrine + chlorpheniramine + atropine) in seasonal allergic rhinitis, not urticaria |
| NCT02082054 | Phase 2 | Unknown | 125 | Dose-ranging of atropine added to pseudoephedrine 120 mg + chlorpheniramine 8 mg in seasonal allergic rhinitis, not urticaria |
| NCT03296358 | NA | Completed | 75 | Randomized, double-blind trial of adding a short corticosteroid burst to conventional H1-antihistamine treatment. Chlorpheniramine is at most background therapy |
None of these trials tests chlorpheniramine for urticaria, so they do not raise the evidence level above L3.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39265704 | 2024 | Randomised phase I trial | Eur J Pharm Sci | Compared oral bilastine, parenteral dexchlorpheniramine and a new parenteral bilastine on histamine-induced wheal and flare. Dexchlorpheniramine is a related enantiomer |
| 35652393 | 2024 | Review | Curr Rev Clin Exp Pharmacol | Comprehensive review of chlorpheniramine, listing chronic urticaria among its clinical uses |
| 7528133 | 1994 | Review | Drugs | Loratadine was as effective as several antihistamines, including chlorpheniramine, in comparative studies |
| 1683523 | 1991 | Review | Ann Allergy | Compares second-generation H1 antihistamines with first-generation agents, which are more sedating and anticholinergic |
| 1981354 | 1990 | Review | Drugs | Cetirizine review covering chronic urticaria (indirect evidence) |
| 1715267 | 1991 | Review | Drugs | Acrivastine review: effective for chronic urticaria in double-blind trials (indirect evidence) |
| 8808167 | 1996 | Review | Drugs | Ebastine review covering chronic idiopathic urticaria (indirect evidence) |
| 14977391 | 2004 | Review | Drugs | Cetirizine review, including inhibition of histamine-induced wheal and flare (indirect evidence) |
| 31852144 | 2019 | Case report / pharmacovigilance | Medicine | Two cases of chlorpheniramine-induced anaphylaxis and a pharmacovigilance review (safety signal) |
| 26240795 | 2015 | Case report | Asia Pac Allergy | Chlorpheniramine-induced anaphylaxis diagnosed by basophil activation test (safety signal) |
Most of the literature concerns other antihistamines or is indirect. There is no chlorpheniramine-specific efficacy study in allergic urticaria.
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ANDA040829 | Chlorphen-12 (KVK-Tech) | Tablet, film coated, extended release | Not listed in source data |
| M012 | Pharbechlor (Ulai Health) | Tablet | Not listed in source data |
| M012 | ALLERGY (A-S Medication Solutions) | Tablet | Not listed in source data |
| M012 | Allergy Relief (WinCo Foods) | Tablet | Not listed in source data |
| M012 | Allergy (Marc Glassman) | Tablet, coated | Not listed in source data |
There are 20 authorizations in total; the five above are shown. Products are mainly oral tablets, with a liquid form also listed.
Safety Considerations
- Hypersensitivity: Rare cases of chlorpheniramine-induced anaphylaxis and immediate hypersensitivity are reported in the literature, one with aspirin intolerance. Screen for prior antihistamine hypersensitivity.
Package insert warnings, contraindications and interaction data were not obtained. Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: H1 blockade is mechanistically direct for allergic urticaria, and the drug is widely marketed in the US. However, the retrieved trials all address allergic rhinitis or use chlorpheniramine as background therapy, and no chlorpheniramine-specific urticaria efficacy study was found. Evidence is therefore capped at L3.
To proceed, the following is needed:
- Confirm the original approved indications from the package insert and label data
- Obtain package insert warnings and contraindications for safety screening (the blocking data gap)
- Verify whether any retrieved trial has a chlorpheniramine arm in urticaria, or search for such trials
- Compare against second-generation antihistamines, which current guidelines favor, to define chlorpheniramine’s role
Other predictions (lower priority):
- Cold urticaria (score 99.13%, L3): a small 1977 double-blind study compared chlorpheniramine, cyproheptadine and placebo. Its clinical value is largely historical.
- Nasal cavity disease (99.53%, L4): support comes from animal models only, and the disease term needs narrowing.
- Acute laryngopharyngitis (99.50%, L5): no supporting evidence, so Hold.
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.