Doxylamine
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Doxylamine: From Allergic Rhinitis and Urticaria to Allergic Urticaria
One-Sentence Summary
Doxylamine is a first-generation H1 antihistamine, originally used for allergic and vasomotor rhinitis, the common cold, allergic conjunctivitis and urticaria/angioedema. The TxGNN model predicts it may be effective for allergic urticaria, but this is mostly an overlap with an existing indication. There are currently 0 clinical trials and 0 publications supporting this specific prediction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Allergic rhinitis, vasomotor rhinitis, pharyngitis, common cold, allergic conjunctivitis, urticaria, angioedema (from the knowledge graph; no approved-indication text is available on the Singapore licences) |
| Predicted New Indication | Allergic urticaria |
| TxGNN Prediction Score | 99.85% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, doxylamine is a first-generation H1 antihistamine with anticholinergic and sedative properties. H1 receptor blockade is a standard approach for histamine-mediated skin reactions.
Urticaria and angioedema are already among doxylamine's original indications, so allergic urticaria is mechanistically consistent with its known use. The very high TxGNN score mostly reflects this overlap with an existing indication rather than a genuinely new repurposing opportunity.
Other top-ranked predictions follow the same pattern:
- Nasal cavity disease, acute laryngopharyngitis and cold urticaria (ranks 2–4, scores 99.3–99.4%) overlap with existing rhinitis, pharyngitis, cold and urticaria indications. Any benefit would be symptomatic.
- Recalcitrant atopic dermatitis (97.5%): sedation may relieve itch and sleep disturbance, but the underlying disease is not treated.
- Rosacea conjunctivitis, trigeminal autonomic cephalalgia and faucial diphtheria have weak or no mechanistic rationale. Oral anticholinergic effects could worsen dry eye in rosacea-related ocular disease.
- Headache disorder (83.2%) is the only prediction with any literature, and that literature is indirect (see below).
Clinical Trial Evidence
Currently no related clinical trials registered for allergic urticaria.
Literature Evidence
No literature is available for allergic urticaria. For the ninth-ranked prediction (headache disorder), the following indirect publications were found:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 25822385 | 2015 | Review | American Family Physician | Practical selection of antiemetics; antihistamines and anticholinergics work best for vestibular-mediated nausea |
| 29671128 | 2018 | Phase 1 PK/PD study | Drugs in R&D | Intranasal doxylamine in subjects with chronic intermittent sleep impairment, aiming for faster onset and fewer side effects than oral tablets |
| 17474541 | 2007 | Clinical study (combination product) | Int J Clin Pharmacol Ther | Single evening dose of a paracetamol, dextromethorphan, doxylamine and ephedrine syrup for multiple cold symptoms |
| 787738 | 1976 | Clinical study (double-blind crossover) | Med J Aust | Mersyndol (paracetamol, codeine, doxylamine, caffeine) was significantly better than placebo for migraine pain relief |
| 24098516 | 2013 | Cohort/Survey | PLoS One | Misuse and dependence on non-prescription codeine analgesics or sedative H1 antihistamines in France |
These studies involve combination products, a PK/PD study, a review and a misuse survey. None shows an independent effect of doxylamine on headache.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN16865P | BONJESTA Extended-Release Tablets 20 mg/20 mg | Tablet, film coated, extended release | Not stated in the available data |
| SIN15301P | DICLECTIN Delayed Release Tablets 10 mg/10 mg | Tablet, delayed release | Not stated in the available data |
Both products are oral, single-ingredient registrations (listed as valid) from Duchesnay Inc.
Safety Considerations
- Contraindications suggested by the knowledge graph (not label text; to be verified against the package insert):
- Eye and urinary: angle-closure glaucoma, ocular hypertension, benign prostatic hyperplasia, bladder neck obstruction
- Cardiovascular: hypertension, coronary artery disease, myocardial infarction, atherosclerosis, ventricular tachycardia
- Hepatic and gastrointestinal: liver disease or failure, pancreatitis, gallbladder disease, peptic ulcer disease
- Metabolic and endocrine: diabetes mellitus, diabetic ketoacidosis, hyperthyroidism (Graves disease, thyrotoxicosis)
- Other: substance abuse or dependence, paracetamol poisoning, hemoglobinopathy
- Drug interactions: 100 interactions were recorded; the first 20 returned include:
- Major: potassium chloride and potassium citrate.
- Moderate: other anticholinergics (atropine, hyoscyamine, scopolamine, glycopyrronium, dicyclomine, propantheline, clidinium, mepenzolate, methscopolamine), opioids (morphine, opium, loperamide, eluxadoline), cannabinoids (dronabinol, nabilone) and metoclopramide. The concern is mainly additive anticholinergic or sedative effects.
- Misuse potential: a French survey found misuse and dependence with sedative H1 antihistamines.
Package insert warnings and contraindications were not available. Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction is supported only by the model score (L5). It largely duplicates indications doxylamine already has, and no trials or literature exist for allergic urticaria. It is not a new repurposing opportunity. Second-generation antihistamines are generally preferred for urticaria.
To proceed, the following is needed:
- Singapore package insert warnings, contraindications and approved indications (the current licence records have no indication text)
- Mechanism of action data
- Doxylamine-specific clinical evidence in urticaria, and a comparison with second-generation antihistamines
- If the headache direction is pursued, independent evidence of a doxylamine effect, since the current studies involve combination products. This is a research question rather than a decision candidate.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.