Promethazine
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Promethazine: From Allergic Rhinitis and Urticaria to Rosacea Conjunctivitis
One-Sentence Summary
Promethazine is a first-generation H1 antihistamine, originally used for allergic conditions such as allergic and vasomotor rhinitis, allergic and other forms of conjunctivitis, urticaria and angioedema. The TxGNN model predicts it may be effective for rosacea conjunctivitis, but the data compiled for this report contain 0 clinical trials and 0 publications for this indication. This prediction rests on model output alone and its mechanistic link is weak.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Vasomotor rhinitis, allergic rhinitis, atopic/papillary/vernal conjunctivitis, urticaria, angioedema (the Singapore licence records contain no indication text, so these come from the knowledge graph) |
| Predicted New Indication | Rosacea conjunctivitis |
| TxGNN Prediction Score | 98.94% |
| Evidence Level | L5 |
| 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. Promethazine is known to be an H1 antihistamine with anticholinergic activity. It is already used for allergic conjunctival disease, and this is the most likely source of the high model score: the prediction probably reflects network proximity to atopic and allergic conjunctivitis in the knowledge graph.
The link to rosacea conjunctivitis is weak. Rosacea-related eye disease is driven mainly by meibomian gland dysfunction, ocular surface inflammation and Demodex, not by histamine. Antihistamine action would therefore be expected to offer little beyond possible symptomatic itch relief. No trials or literature were found to support the prediction.
Other predictions in the list (for context):
| Rank | Predicted Indication | Score | Evidence Level | Comment |
|---|---|---|---|---|
| 2 | Allergic urticaria | 98.13% | L4 | Largely restates an existing labelled use; retrieved literature is indirect |
| 3 | Cold urticaria | 96.87% | L5 | Plausible by H1-antagonist class reasoning; no promethazine-specific evidence |
| 4 | Rhinitis | 94.16% | L3 | Overlaps existing indications; sedation limits use versus newer agents |
| 5 | Recalcitrant atopic dermatitis | 93.24% | L5 | Benefit mainly sedative; guidelines do not support antihistamines for recalcitrant disease |
| 6–10 | Angelucci syndrome, acute hemorrhagic conjunctivitis, parasitic conjunctivitis, chronic follicular conjunctivitis, serous conjunctivitis except viral | 92.9–93.2% | L5 | Model proximity only; no clinical evidence |
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available for rosacea conjunctivitis.
Singapore Market Information
There are 20 valid single-ingredient registrations, all syrup, elixir or injection forms. The licence records contain no approved-indication text. The main authorisations are:
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN16065P | Promezine Syrup 5 mg/5 ml | Syrup | Not recorded |
| SIN10539P | Axcel Promethazine-5 Syrup 5 mg/5 ml | Syrup | Not recorded |
| SIN02481P | Prozine Syrup 5 mg/5 ml | Syrup | Not recorded |
| SIN02707P | DBL Promethazine Hydrochloride Injection BP 50 mg/2 ml | Injection | Not recorded |
| SIN03294P | Xepagan Elixir 10 mg/5 ml | Elixir | Not recorded |
Safety Considerations
Drug Interactions: A total of 100 interactions were identified. Among those listed, the major-level interactions are:
- Bupropion (Major)
- Potassium citrate (Major)
Moderate-level interactions include:
- Anticholinergics: atropine, hyoscyamine, glycopyrronium
- Opioids and antidiarrhoeals: morphine, loperamide
- Antidiabetic agents: metformin, acarbose, alogliptin, canagliflozin, dapagliflozin, chlorpropamide, albiglutide
- Others: epinephrine, famotidine, clarithromycin, lorcaserin, picosulfuric acid, polyethylene glycol with electrolytes
Literature retrieved for other indications also points to sedation and psychomotor impairment as a practical limitation compared with second-generation antihistamines.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction for rosacea conjunctivitis is supported only by the model score. There are no trials or publications, and the mechanism (histamine blockade) does not match the main drivers of the disease. Other top-ranked predictions mostly restate existing allergic indications or lack evidence.
To proceed, the following is needed:
- Singapore package insert warnings and contraindications (a blocking gap for safety screening)
- Mechanism-of-action data
- Evidence that histamine contributes to rosacea-related ocular disease, and any clinical or preclinical studies of antihistamines in this setting
- If a repurposing question is still pursued, reassess the allergic urticaria and rhinitis predictions first, since these have the most (though indirect) literature. They largely restate existing uses, so they would need to be framed as label-extension questions rather than new repurposing.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.