Roxithromycin
| Evidence Level: L5 | Predicted Indications: 8 |
Table of Contents
Roxithromycin: From Bacterial Infections to Leprosy
One-Sentence Summary
Roxithromycin is a macrolide antibiotic, used internationally for respiratory tract, urinary and soft tissue infections. The TxGNN model predicts it may be effective for leprosy, with 0 registered clinical trials and 5 publications (mostly preclinical studies and reviews) currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not specified in the Australian registration data compiled for this report (general use: respiratory tract, urinary and soft tissue infections) |
| Predicted New Indication | Leprosy |
| TxGNN Prediction Score | 0.9970 |
| 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?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known information, roxithromycin is a macrolide antibiotic that inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit. Its in vitro activity is similar to erythromycin, mainly against Gram-positive bacteria and some Gram-negative organisms such as Legionella pneumophila.
Leprosy is caused by Mycobacterium leprae, a bacterial infection, so an antibacterial agent is a mechanistically plausible candidate. Preclinical work supports this. In a mouse footpad model, roxithromycin and clarithromycin were consistently active and bactericidal against M. leprae, whereas erythromycin and azithromycin were inactive. Clarithromycin was superior to roxithromycin in that study. A Japanese review also notes that roxithromycin has anti-inflammatory and immunomodulatory activity alongside anti-M. leprae activity, which may be relevant to leprous neuropathy.
Caveats: the supporting evidence is dominated by preclinical data and by clarithromycin rather than roxithromycin, and no clinical trials of roxithromycin in leprosy were identified.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 1648889 | 1991 | Animal study (mouse) | Antimicrob Agents Chemother | Roxithromycin and clarithromycin were consistently active and bactericidal against M. leprae in mouse footpads; erythromycin and azithromycin were inactive; clarithromycin was superior |
| 3072920 | 1988 | In vitro/animal study | Antimicrob Agents Chemother | Compared newer macrolides with superior pharmacokinetics for activity against M. leprae; builds on earlier erythromycin findings |
| 2665640 | 1989 | In vitro study | Antimicrob Agents Chemother | Rapid macrophage-based screening of over 25 antimicrobial agents for potential antileprosy activity |
| 10481449 | 1999 | Review | Nihon Hansenbyo Gakkai Zasshi | Clarithromycin, roxithromycin, minocycline and fosfomycin have anti-inflammatory and immunomodulatory activity alongside anti-M. leprae activity, relevant to leprous neuropathy |
| 12762831 | 2003 | Review | Am J Clin Dermatol | Guide to macrolide selection in skin infections, including adverse effects and drug interactions |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 11993F | Roxar 300 | Tablet 300 mg | Not available in the data compiled for this report |
Safety Considerations
- Drug Interactions: Pharmacology data identify the motilin receptor (MLNR) as a target of roxithromycin, consistent with the prokinetic (motilin-agonist) activity of macrolides. This is a target interaction and not a drug-drug interaction with a graded severity.
- Potential antagonism with antibody-drug conjugates: A 2023 in vitro study found that macrolide and ketolide antibiotics inhibited the cytotoxic effect of trastuzumab emtansine in HER2-positive breast cancer cells. This is a preclinical signal and not a confirmed clinical interaction.
For full warnings, contraindications and interaction information, please refer to the TGA-approved Product Information (PI).
Conclusion and Next Steps
Decision: Hold
Rationale: The TxGNN score for leprosy is very high, and preclinical studies show roxithromycin has anti-M. leprae activity. However, there are no clinical trials, and the animal data show clarithromycin outperforming roxithromycin. Other predicted indications (for example, congenital malformation syndromes, hypertrichosis and migraine) have no supporting evidence and no plausible mechanism, so they are not recommended for further work. Leprosy is best treated as a research question rather than a candidate ready for clinical adoption.
To proceed, the following is needed:
- Clinical data (at least observational studies or small trials) on roxithromycin in leprosy, and a comparison against clarithromycin and standard multidrug therapy
- Mechanism of action data to support the mechanistic-link analysis
- Approved indication text and safety information (warnings and contraindications) from the Australian Product Information for Roxar 300
- Clarification of the potential interaction with trastuzumab emtansine before any oncology-related consideration
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.