Hydroxyzine
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Hydroxyzine: From Allergic and Atopic Skin and Airway Conditions to Allergic Urticaria
One-Sentence Summary
Hydroxyzine is a first-generation H1 antihistamine, originally used for conditions such as atopic eczema, allergic rhinitis, urticaria and angioedema. The TxGNN model predicts it may be effective for allergic urticaria, with no registered clinical trials and 20 publications retrieved, most of which concern other antihistamines or are class reviews.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Atopic eczema, allergic rhinitis, urticaria, angioedema and related allergic conditions (the Singapore licence records contain no indication text, so this comes from the knowledge-graph indication list) |
| Predicted New Indication | Allergic urticaria |
| TxGNN Prediction Score | 99.77% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 5 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, hydroxyzine is a first-generation H1-receptor inverse agonist. In allergic urticaria, histamine released from mast cells causes the wheal-and-flare response, so H1 blockade is mechanistically direct.
Urticaria and angioedema are already among hydroxyzine's original indications. Allergic urticaria is therefore largely a sub-type of an existing use, not a true repurposing. This limits the novelty of the prediction, although it also makes the prediction biologically sensible.
The 20 retrieved publications are mostly about other antihistamines (bilastine, cetirizine, acrivastine, loratadine, desloratadine) or are class reviews. None is a hydroxyzine-specific trial in allergic urticaria. Cetirizine, a hydroxyzine metabolite, has a large body of urticaria literature, which supports the class effect only indirectly.
Other predicted indications are weaker. Cold urticaria (score 99.66%) has one small 1984 hydroxyzine-specific comparative study (PMID 6480953). Rosacea conjunctivitis, recalcitrant atopic dermatitis, atopic IgE responsiveness, nasal cavity disease, laryngopharyngitis and several non-specific conjunctivitis categories have no retrieved evidence, and their mechanistic links are weak.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Selected from the 20 publications retrieved for allergic urticaria (reviews prioritised, then other types):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 27503042 | 2016 | RCT | Aerosp Med Hum Perform | Cognitive effects of bilastine 20 mg at simulated cabin altitude. It concerns another antihistamine, not hydroxyzine |
| 31582993 | 2019 | Review | Allergy Asthma Clin Immunol | Position statement: newer H1-antihistamines are safer than first-generation ones (including hydroxyzine) and should be first-line for rhinitis and urticaria |
| 28913986 | 2017 | Review | Allergy Asthma Immunol Res | Chronic spontaneous urticaria treatment starts with antihistamines. Hydroxyzine was used in the past, and non-sedating agents are now preferred |
| 16278258 | 2005 | Review | Ann Pharmacother | Efficacy and safety of first- and newer-generation antihistamines in allergic rhinitis and chronic idiopathic urticaria |
| 12113226 | 2002 | Review | Clin Allergy Immunol | H1-antihistamines in children are effective in allergic rhinoconjunctivitis |
| 1981354 | 1990 | Review | Drugs | Cetirizine, a hydroxyzine metabolite, in allergic rhinitis, pollen-induced asthma and chronic urticaria |
| 1715267 | 1991 | Review | Drugs | Acrivastine is effective in chronic urticaria and allergic rhinitis in double-blind trials |
| 7528133 | 1994 | Review | Drugs | Loratadine was as effective as several comparators, including hydroxyzine, in allergic disorders |
| 11034010 | 2000 | Case report | J Clin Gastroenterol | Cetirizine-induced cholestasis, a safety report on the hydroxyzine metabolite |
| 19348661 | 2009 | Case report | J Dermatol | Urticaria exacerbated by H1-antihistamines in one patient |
For cold urticaria, the most relevant hydroxyzine-specific item is PMID 6480953 (1984, J Am Acad Dermatol). It is a small randomised double-blind comparison of cinnarizine, cyproheptadine, doxepin and hydroxyzine in idiopathic cold urticaria, in which doxepin was preferred. The study design is not fully confirmed.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN04142P | AA Pharma Hydroxyzine Capsule 25 mg | Capsule, liquid filled | Not stated in the licence record |
| SIN09981P | Phymorax Tablet 10 mg | Tablet | Not stated in the licence record |
| SIN16328P | Hydroxyzine Mevon Film-Coated Tablets 25 mg | Film-coated tablet | Not stated in the licence record |
| SIN16329P | Hydroxyzine Mevon Film-Coated Tablets 10 mg | Film-coated tablet | Not stated in the licence record |
| SIN04096P | AA Pharma Hydroxyzine Capsule 10 mg | Capsule | Not stated in the licence record |
All five are valid, single-ingredient oral products. None has been cancelled.
Safety Considerations
- Contraindications suggested by the knowledge graph (not taken from label text): hypertension and other cardiovascular disease, coronary artery disease and myocardial infarction, heart conduction disease, sudden cardiac arrest, epilepsy, liver disease, gallbladder disease, hypothyroidism and hyperthyroidism, peptic ulcer disease, open-angle and angle-closure glaucoma, benign prostatic hyperplasia, diabetes and diabetic ketoacidosis, psychotic and other mental disorders, substance abuse or dependence, and hemoglobinopathy.
- Drug interactions: 100 interactions were recorded, and 20 are listed in the data compiled for this report. Major-level interactions include morphine, potassium citrate and dolasetron. Moderate-level interactions include anticholinergic and antispasmodic agents (hyoscyamine, atropine, dicyclomine, trospium), clarithromycin, levofloxacin, loperamide, famotidine, dronabinol and nabilone. Cimetidine is minor. Additive sedation and anticholinergic effects, and QT-related concerns, are the likely themes.
- Class safety concern: the 2019 position statement (PMID 31582993) notes that first-generation antihistamines such as hydroxyzine commonly cause sedation, cognitive impairment, dry mouth, dizziness and orthostatic hypotension. It also links them to accidents, overdoses and sudden cardiac death. It recommends newer-generation agents as first-line.
Please refer to the package insert for official warnings and contraindications, as these were not available in the data compiled for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: Allergic urticaria is mechanistically plausible but largely falls within hydroxyzine's existing use, and there are no registered trials. The retrieved literature is mostly about other antihistamines, and current guidance favours second-generation agents because of hydroxyzine's sedation and anticholinergic burden. The other nine predicted indications are supported by little or no evidence.
To proceed, the following is needed:
- The Singapore package insert, to confirm approved indications and obtain official warnings and contraindications
- Mechanism of action data from DrugBank
- Hydroxyzine-specific trials or comparative data in allergic or cold urticaria, ideally against second-generation antihistamines
- A benefit-risk assessment for older patients and those with cardiovascular, QT-related or anticholinergic-sensitive conditions
- Confirmation of the design of the 1984 cold urticaria study (PMID 6480953)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.