Voriconazole
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Voriconazole: From Invasive Fungal Infections to Multidrug-Resistant Tuberculosis
One-Sentence Summary
Voriconazole is a triazole antifungal agent, established for the treatment of invasive fungal infections such as invasive aspergillosis. The TxGNN model predicts it may be effective for multidrug-resistant tuberculosis (MDR-TB), but this signal is currently supported only by 3 case-level publications describing coincidental fungal-TB co-infection rather than direct treatment evidence, and no registered clinical trials exist for this indication.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Invasive fungal infections (e.g. invasive aspergillosis) — established use of this triazole antifungal; no UK licence-level indication text is available in this evidence pack |
| Predicted New Indication | Multidrug-resistant tuberculosis |
| TxGNN Prediction Score | 98.67% |
| Evidence Level | L5 |
| UK Market Status | Not marketed |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the Evidence Pack. Based on known pharmacology, voriconazole inhibits fungal CYP51 (lanosterol 14α-demethylase), blocking ergosterol synthesis in the fungal cell membrane. This target is specific to fungi and has no known overlap with Mycobacterium tuberculosis, which lacks a sterol-based cell membrane and is not susceptible to azole antifungals.
The supporting literature for this prediction consists of case reports describing patients with tuberculosis who developed a separate, concurrent fungal infection (aspergilloma, invasive aspergillosis, or drug-resistant fungal disease) — not evidence that voriconazole treats tuberculosis itself. In these cases, voriconazole was used to manage the fungal co-infection, while TB was treated with standard anti-tubercular agents. This pattern likely reflects a co-occurrence signal picked up by the model (TB and fungal disease frequently appear together in the same patients and publications) rather than a genuine pharmacological repurposing opportunity.
Given the absence of a plausible mechanistic link and the confounded nature of the available literature, this prediction should be treated as a hypothesis-generating signal only, not as a basis for further clinical development at this time.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 18992166 | 2008 | Case Report | Cases Journal | Diabetic patient with MDR-TB who developed concurrent aspergilloma and invasive aspergillosis; illustrates co-infection rather than voriconazole efficacy against TB |
| 37145297 | 2023 | Case Report (in vitro) | Brazilian Journal of Microbiology | In vitro study of photodynamic inactivation against multidrug-resistant fungal pathogen causing chromoblastomycosis; unrelated to tuberculosis treatment |
| 39359062 | 2024 | Lab/Genetic Study | Virulence | Genetic diversity study of azole-resistant Candida krusei isolates; no tuberculosis-related content |
UK Market Information
No MHRA marketing authorisation is currently held for voriconazole in this evidence pack (market status: Not marketed; total licences: 0). No product, dosage form, or approved indication data is available.
Safety Considerations
Please refer to the SmPC and BNF for safety information. Report suspected adverse reactions via the Yellow Card Scheme.
Note: Key warnings, contraindications, and drug interaction data for voriconazole were not available in this Evidence Pack (flagged as a Blocking data gap — MHRA labelling has not yet been retrieved).
Conclusion and Next Steps
Decision: Hold
Rationale: The top-ranked prediction (MDR-TB) lacks a plausible mechanism of action — voriconazole’s antifungal CYP51 target has no known relevance to M. tuberculosis — and the supporting literature reflects fungal-TB co-infection management rather than anti-tubercular efficacy. With no clinical trials and only L5 (model-prediction-only) evidence, this candidate does not meet the threshold to proceed.
To proceed, the following is needed:
- Resolution of Blocking data gap DG001 (MHRA/SmPC warnings and contraindications) before any safety review can begin
- Resolution of High-priority data gap DG002 (confirmed mechanism of action) to properly assess mechanistic plausibility
- Independent pharmacological or in vitro evidence of any direct anti-mycobacterial activity for voriconazole, which is not currently expected given its known mechanism
- Separate evaluation of two lower-ranked but more mechanistically coherent signals surfaced in this pack, which were miscategorised under TB-related disease labels and may warrant reformulation as distinct research questions: (1) voriconazole for CNS fungal granulomas (e.g. Cladophialophora bantiana infection) that clinically mimic tuberculoma, and (2) voriconazole for chronic pulmonary aspergillosis arising in lung cavities left by prior (inactive) tuberculosis
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.