Fluconazole
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Fluconazole: From Candidiasis to Punctate Epithelial Keratoconjunctivitis
One-Sentence Summary
Fluconazole is an azole antifungal originally used to treat candidiasis (oral, oesophageal, vaginal and invasive forms) and cryptococcal meningitis. The TxGNN model predicts it may be effective for punctate epithelial keratoconjunctivitis, but no clinical trials and no publications currently support this prediction, so it remains a model-only signal.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Oral candidiasis, candidiasis, vulvovaginal candidiasis, oesophageal candidiasis, cryptococcal meningitis, candidaemia, disseminated candidiasis (the Singapore licence records contain no indication text, so these come from the knowledge graph) |
| Predicted New Indication | Punctate epithelial keratoconjunctivitis |
| TxGNN Prediction Score | 99.24% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 9 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, fluconazole is an azole antifungal that is generally understood to inhibit fungal ergosterol synthesis. Its efficacy in superficial and invasive fungal infections is established, but this general knowledge is not supported by mechanism data compiled for this report.
The link to the predicted indication is weak. Punctate epithelial keratoconjunctivitis is often viral or inflammatory in origin, so an antifungal rationale is not apparent. The high score (99.24%, rank 8,703) most likely reflects patterns in the knowledge graph rather than a demonstrated biological connection. This should be treated as a model prediction only.
For context, the other top-ranked predictions are also weakly supported. Plasmodium falciparum malaria has only in vitro evidence. Pneumocystosis has no fluconazole-specific trial, and Pneumocystis is not reliably susceptible to azoles. The remaining predictions have no supporting evidence.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN06804P | DIFLUCAN CAPSULE 100 mg | Capsule | Not stated in licence record |
| SIN04460P | DIFLUCAN CAPSULE 150 mg | Capsule | Not stated in licence record |
| SIN05770P | DIFLUCAN FOR INFUSION 2 mg/ml | Injection | Not stated in licence record |
| SIN15044P | FLUCONAZOLE KABI SOLUTION FOR INFUSION 2MG/ML | Infusion solution | Not stated in licence record |
| SIN14781P | FLUCONAZOLE B.BRAUN SOLUTION FOR INFUSION 2MG/ML | Infusion solution | Not stated in licence record |
Nine valid single-ingredient licences exist in total. The remaining four are Apo-Fluconazole 150 mg (SIN13329P), Medoflucon 150 (SIN12599P), Medoflucon 50 (SIN12600P) and Omastin 50 mg (SIN13067P), all capsules. Available forms are oral (capsule) and injectable (infusion solution, injection). No topical or ophthalmic product is registered.
Safety Considerations
- Contraindication signals from the knowledge graph (not label text): long QT syndrome, familial long QT syndrome, kidney disease, pyoureter, liver disease, gallbladder disease.
- Drug Interactions: 100 interactions were identified. The main ones are:
- Major: chlorpropamide.
- Moderate: famotidine, rabeprazole, omeprazole, dexlansoprazole, hydrocortisone, dexamethasone, betamethasone, triamcinolone, budesonide, loperamide, aprepitant, saxagliptin, bisacodyl, picosulfuric acid, and polyethylene glycol with electrolytes.
- Minor: amphotericin B and clarithromycin.
- Published reports also describe fluconazole raising tacrolimus trough levels in kidney transplant recipients (a CYP3A4-related interaction), which warrants monitoring.
Please refer to the package insert for the full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests on the model score alone. There are no trials or publications, and no plausible antifungal mechanism for this largely viral or inflammatory eye condition. Evidence is at the lowest level (L5). No other predicted indication reaches a level that would justify advancing.
To proceed, the following is needed:
- Mechanism of action data, and a mechanistic rationale linking fluconazole to this ocular condition
- A literature and trial search specific to fluconazole in keratoconjunctivitis, including any ophthalmic use
- Package insert warnings and contraindications from the Singapore regulator (HSA)
- Assessment of route feasibility, since no ophthalmic or topical fluconazole product is registered in Singapore
- Review of the QT-prolongation and hepatic or renal safety signals, and of the interaction burden, for the target population
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.