Trimethoprim

Evidence Level: L5

Predicted Indications: 1

Trimethoprim

Pharmacist Assessment Report

Trimethoprim: From Urinary Tract Infection to Punctate Epithelial Keratoconjunctivitis

One-Sentence Summary

Trimethoprim is an antibacterial originally used for urinary tract infections, as well as ear, eye and other infections. The TxGNN model predicts it may be effective for punctate epithelial keratoconjunctivitis, but no clinical trials or publications currently support this specific prediction, so it rests on the model score alone.

Quick Overview

Item	Content
Original Indication	Urinary tract infection, infectious otitis media, pneumocystosis, shigellosis, conjunctivitis (indication text is not recorded in the Australian licence data)
Predicted New Indication	Punctate epithelial keratoconjunctivitis
TxGNN Prediction Score	0.9957
Evidence Level	L5
Australia Market Status	Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data
Number of PBS Items	1 (valid: 1)
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available. Based on known information, trimethoprim is a dihydrofolate reductase (DHFR) inhibitor antibacterial. Its efficacy in bacterial infections, including conjunctivitis (usually as a topical combination with polymyxin B), is established.

Punctate epithelial keratoconjunctivitis is often viral (for example adenoviral) or inflammatory in origin. An antibacterial would not be expected to act on those causes. The high TxGNN score likely reflects network proximity to the approved conjunctivitis indications rather than a distinct mechanism. Only a possible role against secondary bacterial infection is plausible.

Clinical Trial Evidence

Currently no related clinical trials registered for punctate epithelial keratoconjunctivitis.

Literature Evidence

Currently no related literature available for this predicted indication.

For context, the data compiled for this report include literature on the already-established indication of conjunctivitis, which is not new evidence for the predicted indication:

PMID	Year	Type	Journal	Key Findings
19043945	2008	RCT	J Pediatr Ophthalmol Strabismus	Polymyxin B/trimethoprim ophthalmic solution compared with moxifloxacin for speed of clinical efficacy in bacterial conjunctivitis
30007329	2018	Systematic review/Meta-analysis	J Pediatric Infect Dis Soc	Antibiotic treatments, including trimethoprim, for neonatal chlamydial conjunctivitis
6204534	1984	Clinical study	Am J Ophthalmol	Trimethoprim-containing ophthalmic solutions in bacterial conjunctivitis or blepharitis
8595639	1995	Survey	Clin Ther	Children with acute bacterial conjunctivitis treated with trimethoprim-polymyxin B ophthalmic solution

Australia Market Information

ARTG Number	Product Name	Dosage Form	Approved Indication
ARTG 10785P	Alprim	Tablet 300 mg (oral)	Not recorded in the data compiled for this report

The only listed Australian product is an oral tablet. The predicted ocular indication would likely need a topical ophthalmic formulation, and no route compatibility assessment is available.

Cytotoxicity

Not applicable. Trimethoprim is not an antineoplastic drug, so this section is omitted.

Safety Considerations

Product Information warnings and contraindications were not available. The following come from the drug’s knowledge-graph relationships and from interaction screening, and should be confirmed against the TGA-approved Product Information (PI).

Disease-level contraindications (knowledge graph, not label text): porphyria (including inherited porphyria and other porphyrin metabolism disorders), kidney disease, liver disease, gallbladder disease, thrombocytopenia, neutropenia, agranulocytosis, G6PD deficiency, folic acid deficiency anaemia, Clostridium difficile colitis, perinatal necrotising enterocolitis, glycogen storage disease, cystinuria, galactosaemia and pyoureter.
Drug Interactions (100 interactions identified; selected examples):
- Major: potassium citrate, potassium bicarbonate, potassium chloride, potassium gluconate (hyperkalaemia risk).
- Moderate: metformin, pioglitazone, rosiglitazone, repaglinide, balsalazide, picosulfuric acid, sapropterin.
Other considerations from the prediction analysis: trimethoprim-sulfamethoxazole is a recognised cause of drug-induced vasculitis and hypersensitivity, and carries a risk of hyperkalaemia and renal effects.

Conclusion and Next Steps

Decision: Hold

Rationale: The prediction has no trials or literature behind it (L5). The proposed indication is often viral or inflammatory, so a DHFR-inhibiting antibacterial has no clear mechanistic role. The only Australian product is an oral tablet.

To proceed, the following is needed:

Mechanism of action data and a clear causal link (bacterial versus viral or inflammatory aetiology) for punctate epithelial keratoconjunctivitis
Evidence from clinical studies in this condition, including any registered trials (ClinicalTrials.gov or ANZCTR)
Route and formulation assessment (a topical ophthalmic product versus the registered oral tablet)
TGA Product Information warnings and contraindications to complete the safety review

Other Predicted Indications (Brief Notes)

| Rank | Predicted Indication | Score | Evidence Level | Decision | Note | |—|—|—|—|—|—|

Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.