Colchicine
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Colchicine: From Gout and Familial Mediterranean Fever to Plasmodium falciparum Malaria
One-Sentence Summary
Colchicine is an established oral drug, described in the literature mainly for gout and familial Mediterranean fever (FMF). The TxGNN model predicts it may be effective for Plasmodium falciparum malaria, but there are 0 clinical trials and only 6 publications, all laboratory or observational work, and none of them tests colchicine itself.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the SAHPRA registration data; literature describes gout and FMF |
| Predicted New Indication | Plasmodium falciparum malaria |
| TxGNN Prediction Score | 99.60% |
| Evidence Level | L4 |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 3 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the Evidence Pack. Colchicine is a well-known tubulin binder that disrupts microtubule polymerisation. Several laboratory studies show that compounds binding to the parasite’s cytoskeleton, including tubulin, can inhibit P. falciparum growth in vitro. This is the likely basis for the model’s prediction.
The link is weak for three reasons:
- The retrieved papers mostly study other compounds (curcumin, tubulozoles) or cytoskeletal binders in general. One 1990 study notes that colcemid, a colchicine-related compound, affected parasite protein synthesis in a similar way to tubulozoles, but it is not a direct colchicine result.
- Colchicine has a narrow therapeutic index, so concentrations high enough to act on the parasite may be toxic to the host.
- Many effective antimalarials already exist, so the need for a new candidate is low.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 23505424 | 2013 | In vitro | PLoS One | Curcumin disrupts P. falciparum microtubules, giving indirect support to tubulin as a parasite target |
| 7511206 | 1994 | In vitro | Mol Cell Biol | Expressing the parasite pfmdr1 gene in mammalian cells increased chloroquine susceptibility; relates to drug resistance, not colchicine |
| 2221861 | 1990 | In vitro | Antimicrob Agents Chemother | Tubulozoles reduced parasite protein synthesis; colcemid had a similar effect |
| 2670249 | 1989 | In vitro | Cell Biol Int Rep | Tubulin-binding compounds were active against P. falciparum; parasite tubulin appears different from mammalian tubulin (also indexed as PMID 2655935) |
| 6362934 | 1984 | Observational | Clin Exp Immunol | Antibodies to intermediate filaments were found in 82% of 78 acute malaria patients; not a treatment study |
South Africa Market Information
| Registration Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| C665 (ACT 101/1965) | Colchicine houde | Tablet | Not stated in supplied data |
| 41/3.3/0260 | Aspen colchicine ds | Tablet | Not stated in supplied data |
| C0822 (ACT 101) | Aspen colchicine | Tablet | Not stated in supplied data |
All three products are oral tablets. Essential Medicines List (EML) status is not included in the supplied data.
Safety Considerations
Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.
The literature in the Evidence Pack adds that colchicine has a narrow therapeutic index with no clear line between non-toxic, toxic and lethal doses. Accidental toxicity is common and often has a poor outcome (PMID 20586571). This is a major concern for any use at higher antiparasitic doses.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests on model score and indirect laboratory findings on other compounds. There are no clinical trials and no colchicine-specific antimalarial data, and its narrow safety margin and the availability of effective antimalarials weigh against further work.
To proceed, the following is needed:
- Colchicine-specific in vitro data against P. falciparum, including resistant strains, with a comparison of effective concentrations against human-tolerable exposure
- The SAHPRA package insert warnings and contraindications (currently a blocking data gap)
- Mechanism of action data from DrugBank
Note: The second-ranked prediction, familial Mediterranean fever (score 99.38%, evidence level L3, Proceed with Guardrails), is already the standard use of colchicine rather than true repurposing. The supplied evidence for it is reviews and a single-centre series, with no colchicine RCT.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.