Hydroxyzine
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
Hydroxyzine: Rosacea conjunctivitis
One-Sentence Summary
Hydroxyzine is a first-generation H1 antihistamine, originally used for allergic and itch-related conditions such as atopic dermatitis, allergic rhinitis, urticaria, angioedema and allergic conjunctivitis.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Rosacea conjunctivitis |
| TxGNN Prediction Score | 0.9970 |
| Evidence Level | L5 |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| Recommended Decision | Hold (research question only; see Conclusion) |
Why is This Prediction Reasonable?
Hydroxyzine is a first-generation H1-receptor inverse agonist. In urticaria, histamine released from mast cells drives the wheal-and-flare response, so blocking H1 receptors is mechanistically coherent. Detailed mechanism-of-action data were not available in the data compiled for this report, so this explanation rests on the drug’s known class pharmacology.
The relationship between the original and predicted indications is very close. Urticaria and angioedema are already among hydroxyzine’s established uses, so “allergic urticaria” is better seen as a subtype or synonym of an approved use than as a true repurposing target. The high TxGNN score is consistent with this.
The literature retrieved is mostly reviews of antihistamines in general and of cetirizine (hydroxyzine’s active metabolite). It does not provide hydroxyzine-specific randomized trial data for this condition.
Other predictions reviewed
| Predicted Indication | TxGNN Score | Evidence Level | Assessment |
|---|---|---|---|
| Rosacea conjunctivitis | 0.9970 | L5 | No trials or literature. Ocular rosacea is driven mainly by meibomian gland dysfunction, inflammation and microbial factors, not histamine, so the rationale is weak. |
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 28913986 | 2017 | Review | Allergy Asthma Immunol Res | Chronic spontaneous urticaria starts with antihistamines at higher-than-usual doses; hydroxyzine was used similarly in the past; omalizumab if inadequate control |
| 31582993 | 2019 | Review (position statement) | Allergy Asthma Clin Immunol | Newer-generation H1 antihistamines are safer than first-generation ones such as hydroxyzine and should be first-line for allergic rhinitis and urticaria |
| 16278258 | 2005 | Review | Ann Pharmacother | Efficacy and safety of first- and newer-generation oral antihistamines for allergic rhinitis and chronic idiopathic urticaria |
| 12113226 | 2002 | Review | Clin Allergy Immunol | H1 antihistamines in children; good evidence for allergic rhinoconjunctivitis |
| 7528133 | 1994 | Review | Drugs | Loratadine was as effective as several antihistamines, including hydroxyzine, in allergic disorders |
| 14680442 | 2004 | Review | Expert Opin Pharmacother | Cetirizine, a hydroxyzine metabolite, in allergic disorders |
| 32127782 | 2020 | Review | Clin Mol Allergy | Cetirizine use in children for allergic rhinitis and chronic spontaneous urticaria |
| 11034010 | 2000 | Case report | J Clin Gastroenterol | Cetirizine-induced cholestasis in a patient without prior liver disease (safety signal for the metabolite) |
| 19348661 | 2009 | Case report | J Dermatol | Urticaria exacerbated by H1 antihistamines in a single patient |
| 6480953 | 1984 | Comparative double-blind study (cold urticaria) | J Am Acad Dermatol | Cinnarizine, cyproheptadine, doxepin and hydroxyzine compared in idiopathic cold urticaria; doxepin preferred by most patients |
India Market Information
Twenty single-ingredient licences are valid and none are cancelled. The records contain no approved-indication text. The first five are listed below.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 104657 | Hdz 25 Tablet | Strip of 10 tablets | Not stated |
| 245911 | Yzin 10 Tablet | Strip of 10 tablets | Not stated |
| 104653 | Hyzox 25 Tablet | Strip of 10 tablets | Not stated |
| 105234 | Hizone 25mg Tablet | Strip of 10 tablets | Not stated |
| 104187 | Hilerin 10mg Tablet | Strip of 10 tablets | Not stated |
Other presentations include 15-tablet strips and a 15 ml oral drop (Azon 6mg Drop).
Safety Considerations
- Drug Interactions: 297 interactions were identified. Major ones include morphine, potassium citrate and dolasetron. Moderate ones include other anticholinergics (atropine, hyoscyamine, dicyclomine, trospium), clarithromycin, levofloxacin, famotidine, loperamide, dronabinol and nabilone.
- Class concerns from the literature: first-generation antihistamines such as hydroxyzine are associated with sedation, cognitive impairment, dry mouth, dizziness and orthostatic hypotension, and have been linked to accidents, overdoses and sudden cardiac death (PMID 31582993).
For full warnings, please refer to the package insert.
Conclusion and Next Steps
Decision: Hold
Rationale: Allergic urticaria is essentially an already-accepted use of hydroxyzine, so it is not a genuine repurposing opportunity. The evidence is limited to reviews, mostly about cetirizine, with no registered trials. Guidelines now prefer second-generation antihistamines because of hydroxyzine’s sedation and anticholinergic burden.
To proceed, the following is needed:
- Package insert warnings and contraindications from the Indian regulatory sources
- Detailed mechanism of action data
- Hydroxyzine-specific controlled trials in urticaria subtypes (particularly cold urticaria), compared with second-generation antihistamines
- A risk–benefit assessment for patients with cardiovascular disease, glaucoma, prostatic hyperplasia or on interacting drugs
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.