Colchicine
| Evidence Level: L4 | Predicted Indications: 3 |
Table of Contents
Colchicine: From Gout to Plasmodium falciparum Malaria
One-Sentence Summary
Colchicine is an established oral anti-inflammatory drug used mainly for gout and familial Mediterranean fever (FMF). The TxGNN model predicts it may be effective for Plasmodium falciparum malaria, but the supporting evidence is very thin: 0 clinical trials and only 5 unique publications, all indirect in vitro or serology work. None of them reports colchicine efficacy in malaria.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Gout and familial Mediterranean fever (per the literature in the pack; label indication text was not supplied) |
| Predicted New Indication | Plasmodium falciparum malaria |
| TxGNN Prediction Score | 99.60% |
| Evidence Level | L4 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
A structured mechanism-of-action record is not available for this drug. The mechanistic hypothesis is that colchicine binds tubulin and disrupts microtubules. Plasmodium parasites depend on microtubules and the cytoskeleton during intraerythrocytic development, so a biological rationale exists.
Older work supports the general idea that cytoskeleton-binding compounds can act against P. falciparum in vitro. One 1990 study found that colcemid, a compound related to colchicine, affected parasite protein synthesis in a way similar to the tubulozoles. That is the closest link in the supplied data, and it is not direct evidence for colchicine.
The link between the original and new indications is weak. Gout and FMF are inflammatory conditions, while malaria is a parasitic infection. The 0.996 score is a computational prediction only. Colchicine’s narrow therapeutic index and the availability of effective antimalarials also weigh against further development.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 23505424 | 2013 | In vitro study | PloS one | Curcumin, not colchicine, disrupts P. falciparum microtubules. It is relevant only as a tubulin-targeting analogy. |
| 7511206 | 1994 | In vitro study | Molecular and cellular biology | Expressing the parasite pfmdr1 gene in mammalian cells increased chloroquine susceptibility. Not about colchicine. |
| 2221861 | 1990 | In vitro study | Antimicrobial agents and chemotherapy | Tubulozoles reduced parasite protein synthesis. Colcemid had a similar effect. |
| 2655935 | 1989 | In vitro study | Cell biology international reports | Tubulin-binding compounds were active against P. falciparum in vitro. Tubulozole-T was proposed as a novel antimalarial candidate. The pack lists this record twice (PMID 2670249). |
| 6362934 | 1984 | Observational/serology study | Clinical and experimental immunology | 82% of acute malaria patients had antibodies to intermediate filaments. Not a treatment study. |
US Market Information
The supplied records do not include approved indication text. Five of the 20 licenses are shown below.
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| ANDA209470 | Colchicine | Tablet, film coated | Mylan Pharmaceuticals Inc. |
| NDA204820 | Colchicine | Capsule | Hikma Pharmaceuticals USA Inc. |
| NDA204820 | Colchicine | Capsule | Coupler LLC |
| ANDA217620 | Colchicine | Capsule | Camber Pharmaceuticals, Inc. |
| NDA204820 | Colchicine | Capsule | A-S Medication Solutions |
All listed forms are oral (tablet and capsule).
Safety Considerations
- Narrow therapeutic index: A 2010 toxicology review (PMID 20586571) reports no clear distinction between nontoxic, toxic, and lethal doses. Unintentional toxicity is common and often has a poor outcome.
Please refer to the package insert for warnings, contraindications, and drug interactions. No drug-interaction records were found in the supplied data.
Conclusion and Next Steps
Decision: Hold
Rationale: The only support for this indication is a high model score and an indirect microtubule rationale. There are no clinical trials and no literature showing colchicine efficacy in malaria. Its narrow therapeutic index and the availability of effective antimalarials weigh against prioritizing it.
To proceed, the following is needed:
- Direct in vitro testing of colchicine against P. falciparum, including potency and selectivity relative to host toxicity
- A targeted literature search for colchicine or colcemid antimalarial data
- Package insert warnings, contraindications, and DDI data to complete safety screening
- Structured MOA data from DrugBank
Note: In this Evidence Pack, familial Mediterranean fever (rank 2, score 99.38%) is a better-supported prediction. Colchicine is already a widely recognized first-line therapy for it, so it is closer to an existing use than to new repurposing.
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before any application.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.