Trimethoprim
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
Trimethoprim: Punctate epithelial keratoconjunctivitis
One-Sentence Summary
Trimethoprim is an antibacterial drug originally used for urinary tract infections and several other infections, including infectious otitis media, pneumocystosis, shigellosis and conjunctivitis. The TxGNN model predicts it may be effective for punctate epithelial keratoconjunctivitis, but no clinical trials and no publications currently support this specific prediction. A second prediction, conjunctivitis, has 19 publications but no registered trials. It largely restates an existing use.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Punctate epithelial keratoconjunctivitis |
| TxGNN Prediction Score | 0.9957 |
| Evidence Level | L5 |
| India Market Status | Listed in a compiled Indian medicine price dataset (5 of 5) – CDSCO approval status is not included in this data |
| Number of Listed Products | 5 (valid: 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 information, trimethoprim is a dihydrofolate reductase inhibitor. It blocks bacterial folate synthesis and is active against common bacterial pathogens. It is used in ophthalmic solutions, usually combined with polymyxin B, for bacterial conjunctivitis and blepharoconjunctivitis.
The score comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, such as punctate epithelial keratoconjunctivitis and conjunctivitis, not biological evidence. However, this condition is often viral (e.g., adenoviral) or immune-mediated. An antibacterial mechanism would therefore have limited relevance, and the link is speculative.
Conjunctivitis is already among trimethoprim’s original indications. It is therefore not a prediction and not true repurposing. It does show that the drug is supported for bacterial eye infections.
Clinical Trial Evidence
Currently no related clinical trials registered, for either predicted indication.
Literature Evidence
No literature was found for punctate epithelial keratoconjunctivitis. The table below covers the most relevant records for the related conjunctivitis prediction. Several other records were mostly veterinary studies, unrelated case reports or reviews, and are omitted.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 30007329 | 2018 | Systematic review/Meta-analysis | J Pediatric Infect Dis Soc | Antibiotic treatments, including oral trimethoprim, for neonatal chlamydial conjunctivitis |
| 19043945 | 2008 | Multicenter comparative study (design to be verified) | J Pediatr Ophthalmol Strabismus | Polymyxin B/trimethoprim vs 0.5% moxifloxacin ophthalmic solution: speed of clinical efficacy in bacterial conjunctivitis |
| 6204534 | 1984 | Clinical evaluation (design to be verified) | Am J Ophthalmol | Efficacy and safety of trimethoprim-containing ophthalmic solutions (with sulfacetamide and polymyxin B) in bacterial conjunctivitis or blepharitis |
| 8595639 | 1995 | Survey | Clin Ther | Children with acute bacterial conjunctivitis treated with trimethoprim-polymyxin B ophthalmic solution |
| 2418736 | 1985 | Clinical study | Ann Ophthalmol | Trimethoprim-polymyxin B in surface ocular bacterial infections, compared with a multi-component combination |
| 20084257 | 2001 | Review | Paediatr Child Health | Etiology, clinical features and management of acute infectious conjunctivitis in children |
| 16491721 | 2006 | Review | J Pediatr Ophthalmol Strabismus | Controlling contagious bacterial conjunctivitis and limiting transmission |
India Market Information
The India licences listed no approved indication text. All five are valid single-ingredient oral tablets.
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| 218088 | Tmp 300mg Tablet | Strip of 10 tablets | Jagsonpal Pharmaceuticals Ltd |
| 25913 | Bacstol 200 Tablet | Strip of 10 tablets | Ipca Laboratories Ltd |
| 116418 | Keno 200mg Tablet | Strip of 10 tablets | Mancare Labs Pvt Ltd |
| 25893 | Bacstol Tablet | Strip of 10 tablets | Ipca Laboratories Ltd |
| 138103 | Metstol 100mg Tablet | Strip of 10 tablets | Renauxe Pharma India Pvt Ltd |
No ophthalmic formulation is registered among these licences, so route compatibility with an eye indication is unconfirmed.
Safety Considerations
- Contraindications (from TxGNN model (deep learning) associations, not label text; these may reflect similarities the model learned between related diseases, not biological evidence): inherited porphyria and other porphyrias, kidney disease, liver disease, thrombocytopenia, neutropenia, agranulocytosis, G6PD deficiency, folic acid deficiency anaemia, Clostridium difficile colitis, perinatal necrotizing enterocolitis, gallbladder disease, glycogen storage disease, cystinuria, galactosemia and pyoureter.
- Drug Interactions: 106 interactions were identified.
- Major: potassium citrate, potassium bicarbonate, potassium chloride and potassium gluconate. These raise a risk of hyperkalaemia.
- Moderate: metformin, pioglitazone, rosiglitazone, repaglinide, balsalazide, picosulfuric acid and sapropterin.
- Several others have an unclassified severity.
Please refer to the package insert for label warnings, as these were not available.
Conclusion and Next Steps
Decision: Hold
Rationale: The TxGNN score for punctate epithelial keratoconjunctivitis is very high, but there are no trials or publications for it. The likely cause of the condition (viral or immune-mediated) also makes an antibacterial effect doubtful. The conjunctivitis prediction has supporting literature (L3), but it is an existing indication rather than a new one.
To proceed, the following is needed:
- Package insert warnings and contraindications from India sources (currently a blocking gap for safety screening)
- Confirmed mechanism-of-action data from DrugBank
- Targeted literature and trial searches for punctate epithelial keratoconjunctivitis, including its causes (bacterial vs viral)
- Verification of the design and results of the two ophthalmic solution studies (PMIDs 19043945 and 6204534)
- Assessment of ophthalmic formulation availability, since the registered products are oral tablets only
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.