Itraconazole
| Evidence Level: L4 | Predicted Indications: 1 |
Table of Contents
Itraconazole: From Fungal Infections to Pneumocystosis
One-Sentence Summary
Itraconazole is an azole antifungal. The Evidence Pack does not record its approved indications, so “fungal infections” reflects its known drug class. The TxGNN model predicts it may be effective for Pneumocystosis, but there are 0 clinical trials and 20 publications, and none of the publications tests itraconazole as anti-Pneumocystis therapy. The prediction is graph-based only, and this evaluation recommends Hold.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not listed in the record (itraconazole is a known azole antifungal) |
| Predicted New Indication | Pneumocystosis |
| TxGNN Prediction Score | 99.34% |
| Evidence Level | L4 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 14 licenses (NDA and ANDA) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
The prediction is only weakly supported. Mechanism of action data is not available in the Evidence Pack. Itraconazole is known to inhibit fungal CYP51 (lanosterol 14-alpha-demethylase), which blocks ergosterol synthesis in the fungal cell membrane.
That mechanism does not fit Pneumocystosis well. Pneumocystis jirovecii has little or no ergosterol in its membrane, since cholesterol predominates, and azoles are not established as effective against it. The standard agents are TMP-SMX, pentamidine, atovaquone and primaquine-clindamycin.
The literature links most likely reflect co-occurrence. Itraconazole is often given as mould-active prophylaxis alongside TMP-SMX in transplant, HIV and chronic granulomatous disease (CGD) patients. Both organisms therefore appear in the same papers, but itraconazole is not being tested against Pneumocystis. The high TxGNN score (0.993) appears to reflect this graph-level association rather than a demonstrated therapeutic effect.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 11737382 | 2001 | RCT | HIV Medicine | Double-blind, placebo-controlled phase III trial of itraconazole prophylaxis against deep fungal infections in HIV-infected patients. It addresses fungal prophylaxis, not Pneumocystosis. |
| 2121456 | 1990 | Review | Drugs | Summary of therapy and prophylaxis for systemic protozoan infections, including Pneumocystis carinii. |
| 21418688 | 2010 | Review | BMJ Clinical Evidence | Primary and secondary prophylaxis of opportunistic infections in HIV. |
| 8397916 | 1993 | Review | Current Clinical Topics in Infectious Diseases | Prophylaxis and treatment of infection in bone marrow transplant recipients. |
| 21973267 | 2011 | Review | Clinical Pharmacokinetics | Penetration of antifungal and other anti-infective agents into pulmonary epithelial lining fluid. This is pharmacokinetic background only. |
| 26036497 | 2015 | Cohort | Transplantation Proceedings | Single-center experience of invasive fungal infections after kidney transplantation. |
| 17594870 | 2007 | Cohort | Allergologia et Immunopathologia | 25 years of experience with chronic granulomatous disease in pediatric patients, a population with fungal infections. |
| 30429396 | 2018 | Cohort | Indian Journal of Medical Microbiology | Respiratory fungal pathogens in immunocompetent and immunocompromised hosts, in relation to CD4 counts. |
| 22273250 | 2012 | Retrospective study | Leukemia & Lymphoma | Non-bacterial infections in 182 Asian patients treated with alemtuzumab. |
| 36891307 | 2023 | Case report | Frontiers in Immunology | Talaromyces marneffei and Pneumocystis jirovecii coinfection in a child with a STAT1 mutation. |
US Market Information
| Authorization Number | Product Name | Dosage Form |
|---|---|---|
| NDA208901 | Tolsura | Capsule, gelatin coated |
| NDA020083 | itraconazole | Capsule |
| ANDA208591 | Itraconazole | Capsule, coated pellets |
| ANDA212239 | Itraconazole | Solution |
| ANDA206741 | ITRACONAZOLE | Capsule |
There are 14 licenses in total; the five above are shown. Approved indication text is not available in the record.
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests only on a graph-based score, with no registered clinical trials and no publication testing itraconazole against Pneumocystis. The known mechanism (ergosterol synthesis inhibition) does not fit an organism with little or no membrane ergosterol, and established agents already exist.
To proceed, the following is needed:
- Preclinical or in vitro evidence of itraconazole activity against Pneumocystis jirovecii
- Package insert warnings and contraindications for safety screening
- Mechanism of action data, for example from DrugBank
- Approved indication text from the US labels, to confirm the original indication
- Evidence that any clinical benefit is not just a co-administration effect with TMP-SMX
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.