Chloramphenicol
| Evidence Level: L5 | Predicted Indications: 8 |
Table of Contents
Chloramphenicol: Diffuse scleroderma
One-Sentence Summary
Chloramphenicol is a broad-spectrum antibiotic. The TxGNN model predicts it may be associated with diffuse scleroderma, with a score of 0.9965. There are no clinical trials and 4 publications in the data compiled for this report. All 4 are preclinical laboratory studies of scleroderma fibroblasts, and none tests chloramphenicol as a treatment, so the evidence is very weak.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Diffuse scleroderma |
| TxGNN Prediction Score | 0.9965 |
| 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. Chloramphenicol is generally known as an antibiotic that blocks protein synthesis in bacteria. This is an antibacterial action, and it has no recognised link to the fibrotic and autoimmune processes in diffuse scleroderma.
The four retrieved papers describe collagen gene regulation (the alpha1(I) procollagen gene), Smad3/Sp1/p300 signalling and TGF-beta blockade in scleroderma fibroblasts. None of the titles shows chloramphenicol being tested as a treatment. The link is likely incidental, for example the use of the chloramphenicol acetyltransferase (CAT) reporter gene assay in these experiments, rather than a pharmacological effect. The high prediction score is therefore probably an artefact of the model, and no pharmacological rationale supports it.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 8702443 | 1996 | In vitro mechanistic study | Arthritis and Rheumatism | Transcriptional activation of the alpha1(I) procollagen gene in dermal fibroblasts from patients with recent-onset diffuse systemic sclerosis; role of intronic sequences |
| 16319104 | 2006 | In vitro mechanistic study | Rheumatology (Oxford) | Role of TGF-beta/Smad signalling in increased collagen gene expression in scleroderma fibroblasts; Smad3 interacts with Sp1 and p300 |
| 9811061 | 1998 | In vitro mechanistic study | Arthritis and Rheumatism | Promoter elements of the alpha1(I) procollagen gene involved in its up-regulated expression in systemic sclerosis |
| 11229480 | 2001 | In vitro mechanistic study | Arthritis and Rheumatism | Blocking TGF-beta signalling prevented up-regulated collagen synthesis in scleroderma fibroblasts |
None of these studies evaluates chloramphenicol as a treatment for diffuse scleroderma.
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 11112W | Chlorsig | Eye drops 5 mg per mL, 10 mL | Not recorded in the local data |
The only licence in the local data is a single-ingredient ophthalmic (eye drop) product, and it is currently valid. No systemic or oral formulation is recorded.
Safety Considerations
Detailed label warnings and contraindications are not available in the data compiled for this report. Please refer to the TGA-approved Product Information (PI) for full safety information.
- Blood and bone marrow conditions: Related records list thrombocytopenia, anaemia, aplastic anaemia, agranulocytosis and neutropenia as conditions of concern. Chloramphenicol is known for haematological toxicity, which would matter for any systemic use.
- Other conditions of concern in related records: kidney disease, liver disease, gallbladder disease, peripheral neuropathy, optic neuritis, acute intermittent porphyria and paroxysmal nocturnal haemoglobinuria.
- Drug interactions: Interaction records were found for 100 drugs. Two are rated Major: cisapride and naloxegol. Examples rated Moderate include sulfonylureas (glimepiride, glipizide, glyburide, chlorpropamide, acetohexamide), repaglinide, saxagliptin, simvastatin, rosuvastatin, metronidazole, aprepitant, budesonide and iron.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests on a model score alone. The four publications are laboratory studies of scleroderma fibroblasts that do not test chloramphenicol, and no clinical trials exist. There is no plausible pharmacological link, and the drug’s known haematological toxicity adds concern for any systemic use. The only Australian product is an eye drop.
To proceed, the following is needed:
- Evidence that chloramphenicol itself has an effect on collagen synthesis or fibrosis (for example, direct preclinical testing)
- Confirmation that the literature link is not simply use of the CAT reporter assay
- Mechanism of action data
- Label warnings and contraindications from the TGA-approved Product Information
- A route and formulation assessment, since the only local product is an ophthalmic preparation and diffuse scleroderma would need systemic treatment
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.