Sulfamethoxazole
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
- Sulfamethoxazole
- Sulfamethoxazole: From Bacterial and Parasitic Infections to Acute Contagious Conjunctivitis
Sulfamethoxazole: From Bacterial and Parasitic Infections to Acute Contagious Conjunctivitis
One-Sentence Summary
Sulfamethoxazole is a sulfonamide antibacterial, originally used for infections such as otitis media, nocardiosis, toxoplasmosis, pneumocystosis, shigellosis and conjunctivitis. The TxGNN model predicts it may be effective for acute contagious conjunctivitis, but no clinical trials and only 1 publication (a bacterial susceptibility study) currently support this direction. Conjunctivitis is already among the drug's listed original indications, so this is not a true repurposing candidate.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Infectious otitis media, nocardiosis, toxoplasmosis, pneumocystosis, shigellosis, conjunctivitis and others (the Singapore licence records contain no indication text) |
| Predicted New Indication | Acute contagious conjunctivitis |
| TxGNN Prediction Score | 99.63% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 12 |
| 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 pharmacology, sulfamethoxazole is a sulfonamide that blocks bacterial folate synthesis by inhibiting dihydropteroate synthase. It is commonly used together with trimethoprim, and its efficacy in several bacterial and protozoal infections is established.
Acute contagious conjunctivitis is usually bacterial, so an antibacterial folate-pathway mechanism is biologically plausible. Conjunctivitis is already listed as an original indication, so the prediction mostly restates existing use rather than proposing a new one.
The remaining nine predictions are weaker. Several (punctate epithelial keratoconjunctivitis, endocardial fibroelastosis, postinfectious vasculitis, post-infectious syndrome) involve viral, immune-mediated or fibrotic processes with little antibacterial rationale. Ulcerative blepharitis and blepharoconjunctivitis are plausible because they overlap with bacterial eye infections, but they have no supporting data. Parasitic eyelid infestation links loosely to the listed myiasis and hirudiniasis indications, but it is a prediction only.
Clinical Trial Evidence
Currently no clinical trials are registered for acute contagious conjunctivitis.
For other predicted indications, the trials found were consistent with existing antibacterial uses rather than new ones. The most relevant are listed below, all under "post-bacterial disorder" (rank 6) and "post-infectious syndrome" (rank 8):
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02096159 | NA | Active, not recruiting | 93 | TMP-SMX vs placebo prophylaxis after hypospadias repair (double-blind RCT) |
| NCT02024867 | NA | Completed | 249 | 3 vs 10 days of TMP-SMX after drainage of skin abscesses (non-inferiority) |
| NCT05925309 | NA | Recruiting | 356 | Prophylactic oral antibiotics against cholangitis after Kasai portoenterostomy |
| NCT07619027 | Phase 4 | Not yet recruiting | 1084 | Low-dose vs standard-dose TMP-SMX to prevent Pneumocystis pneumonia after kidney transplantation |
| NCT05106803 | N/A | Completed | 24 | Observational antibiotic susceptibility profile of surgical site infection pathogens |
| NCT01101412 | Phase 1/2 | Withdrawn | 0 | TMP-SMX-based catheter lock solution; withdrawn, no data |
Literature Evidence
Publications retrieved for the top prediction and for exposure keratitis (rank 3):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31788487 | 2019 | Cohort | Med Hypothesis Discov Innov Ophthalmol J | Bacteriology and antibiotic susceptibility of childhood acute bacterial conjunctivitis in Western Greece (indirect evidence, not an efficacy trial) |
| 24244625 | 2013 | Review | PLoS One | Hospital cases of Staphylococcus aureus keratitis, MRSA vs MSSA |
| 22880135 | 2012 | Cohort | PLoS One | Ocular S. aureus infection: methicillin resistance, clinical features and antibiotic susceptibility |
| 28704121 | 2017 | In vitro | J Ocul Pharmacol Ther | In vitro antiamoebic activity of antimicrobials against Acanthamoeba keratitis isolates |
| 3157322 | 1985 | Case report | Am J Ophthalmol | Erythema multiforme after topical sulfacetamide for conjunctivitis, in a child who had earlier tolerated TMP-SMX (a safety signal) |
None of these tests sulfamethoxazole as treatment for the predicted conditions.
Singapore Market Information
All 12 licences are valid single-ingredient registrations. The licence records contain no approved indication text. Five main authorisations:
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN00508P | APO-SULFATRIM PEDIATRIC TABLET | Tablet | Not stated in the licence record |
| SIN00435P | APO-SULFATRIM TABLET | Tablet | Not stated in the licence record |
| SIN00526P | B.S. SUSPENSION | Suspension | Not stated in the licence record |
| SIN02183P | DBL SULFAMETHOXAZOLE 400MG AND TRIMETHOPRIM 80MG CONCENTRATE INJECTION BP | Injection | Not stated in the licence record |
| SIN00583P | CO-TRIMEXAZOLE SUSPENSION | Suspension | Not stated in the licence record |
Available forms cover oral tablets, suspensions and an injection. No ophthalmic formulation is registered.
Safety Considerations
- Contraindications (from the knowledge graph, not label text): porphyria (including inherited porphyria and porphyrin metabolism disease), kidney disease, kidney failure, uremia, glomerulonephritis, liver disease, gallbladder disease, thrombocytopenia, neutropenia, agranulocytosis, G6PD deficiency, folic acid deficiency anaemia, Clostridium difficile colitis, perinatal necrotizing enterocolitis, glycogen storage disease, cystinuria, galactosemia and pyoureter.
- Drug Interactions: The interaction screen returned 100 interactions. Those displayed include:
- Moderate: sulfonylureas (chlorpropamide, glimepiride, glipizide, glyburide, acetohexamide) and insulins (human, aspart, degludec, detemir, glargine, glulisine), with a risk of altered blood glucose control; also balsalazide and picosulfuric acid.
- Minor: famotidine, clarithromycin, cisapride, and the 5-HT3 antagonists dolasetron, palonosetron and granisetron.
- Topical sulfonamide report: One case report describes severe erythema multiforme after topical sulfacetamide for conjunctivitis, which is relevant if any ocular formulation were considered.
Please refer to the package insert for the full warnings, as the label text was not available for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: The top prediction, acute contagious conjunctivitis, overlaps with an existing indication and is supported only by an indirect susceptibility study, with no efficacy trials. The other nine predictions have no direct supporting trials, and several lack a plausible antibacterial mechanism. Label safety information was also unavailable, which blocks safety screening.
To proceed, the following is needed:
- Package insert warnings and contraindications from HSA (a blocking gap)
- Mechanism of action data from DrugBank
- Confirmation of the approved indications for the Singapore licences
- Clinical efficacy data for sulfamethoxazole in bacterial conjunctivitis, and a decision on whether an ocular formulation is relevant, since none is registered
- Further review of the ulcerative blepharitis and blepharoconjunctivitis predictions, which are mechanistically plausible but have no data
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.