Codeine
| Evidence Level: L5 | Predicted Indications: 3 |
Table of Contents
- Codeine
- Pharmacist Assessment Report
- Codeine: From Allergic Rhinitis and Common Cold Symptoms to Nasal Cavity Disease
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- India Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Codeine: From Allergic Rhinitis and Common Cold Symptoms to Nasal Cavity Disease
One-Sentence Summary
Codeine is an opioid medicine originally used for symptom relief in upper respiratory conditions (allergic rhinitis, pharyngitis, common cold) and headache disorders. The TxGNN model predicts it may be effective for nasal cavity disease, but this rests on a very high model score alone: 0 clinical trials and 1 publication (a case report describing an adverse event, not a benefit) are available. The evidence does not currently support a therapeutic repurposing.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Allergic rhinitis, vasomotor rhinitis, pharyngitis, common cold, rhinitis, nasopharyngitis, headache disorder |
| Predicted New Indication | Nasal cavity disease |
| TxGNN Prediction Score | 0.9993 |
| 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 |
Note: The original indications come from the TxGNN model (deep learning), because the approved indication text in the India licence records is blank. These scores may reflect similarities the model learned between related diseases, not biological evidence.
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, codeine is an opioid used mainly for cough suppression and mild pain relief. Its use in upper respiratory symptoms is well established, and mechanistically it acts through mu-opioid receptors in the central nervous system.
The high prediction score comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases such as nasal cavity disease and the approved indications (rhinitis, nasopharyngitis), not biological evidence. This is anatomical and symptomatic adjacency, not proof of benefit. Codeine’s central antitussive and analgesic actions do not address nasal pathology, and no plausible mechanism for treating nasal cavity disease is supported.
The only publication is a case report of a rhinolith (nasal stone) that formed around a hardened codeine and opium foreign body. This is an incidental or adverse event, not a therapeutic effect.
Other predictions in the ranked list show the same pattern:
- Acute laryngopharyngitis: no trials or literature; adjacent to the approved pharyngitis and cold indications. Codeine use in children with upper respiratory conditions is restricted because of ultra-rapid CYP2D6 metabolism risk.
- Trigeminal autonomic cephalalgia (score 0.9943): opioids are not recommended for cluster headache, and the retrieved papers show no codeine benefit. Opioids also carry a risk of medication-overuse headache and dependence.
- Allergic urticaria (score 0.9937): the literature points in the opposite direction. Codeine directly triggers mast-cell histamine release and is used as a positive control in skin tests, so it can provoke urticaria rather than treat it.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 17315836 | 2007 | Case report | Ear, Nose & Throat Journal | A 21-year-old man had a rhinolith formed around a hardened codeine and opium foreign body (“opioma”). It was an unusual cause of nasal obstruction, not a treatment benefit. |
India Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 52843 | Codybex Syrup | Syrup, 100 ml bottle | Not stated in the licence record |
| 43548 | Codifem Syrup | Syrup, 100 ml bottle | Not stated in the licence record |
| 129888 | Lecof-C Syrup | Syrup, 100 ml bottle | Not stated in the licence record |
| 36031 | Codine Sulphate 15mg Tablet | Tablet, strip of 10 | Not stated in the licence record |
| 34726 | Codeine Phosphate Linctus | Linctus, 60 ml bottle | Not stated in the licence record |
Twenty single-ingredient licences are currently valid (none cancelled). Most are syrups, with a few tablet and linctus products.
Safety Considerations
- Contraindication signals from the knowledge graph (not label text): hypertension, liver failure and liver disease, kidney disease, epilepsy, insomnia, chronic obstructive pulmonary disease, anxiety and other mental disorders (including psychotic disorders), porphyria, pancreatitis, gallbladder disease, thrombocytopenia, hypothyroidism, peptic ulcer disease, inflammatory bowel disease, gastritis, and dermatitis herpetiformis.
- Drug interactions: 449 interactions are recorded. The major ones listed are alvimopan and bupropion. Moderate ones include atropine, cimetidine, dexamethasone, dicyclomine, glycopyrronium, hyoscyamine, loperamide, granisetron, dolasetron and fenfluramine.
- Paediatric use: Ultra-rapid CYP2D6 metabolism makes codeine risky in children with upper respiratory conditions.
- Urticaria: Codeine can directly provoke mast-cell degranulation and urticaria, which is relevant for patients with urticaria or asthma.
- Headache: Opioid use carries a risk of medication-overuse headache and dependence.
Package insert warnings and contraindications were not available, so please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The TxGNN score is very high, but the evidence is model prediction only (L5), with no clinical trials and a single case report that describes an adverse event. There is no plausible mechanism for benefit in nasal cavity disease, and codeine has meaningful safety concerns.
To proceed, the following is needed:
- Package insert warnings and contraindications from the India regulator, which are required before any safety screening
- Mechanism of action data (for example, from DrugBank)
- Any controlled clinical evidence showing therapeutic benefit in nasal cavity disease, which does not currently exist
- A review of the paediatric and respiratory risks, and the mast-cell and urticaria signal, if the project continues
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.