Tafenoquine
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
Tafenoquine: From Malaria to Smouldering Systemic Mastocytosis
One-Sentence Summary
Tafenoquine is an antimalarial drug, originally used to treat and prevent malaria. The TxGNN model predicts it may be effective for Smouldering Systemic Mastocytosis, but no clinical trials and no publications currently support this direction, so the prediction rests on model output alone.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Malaria |
| Predicted New Indication | Smouldering systemic mastocytosis |
| TxGNN Prediction Score | 99.05% |
| Evidence Level | L5 |
| US Market Status | Cancelled only (no currently valid licenses) |
| Number of NDAs | 2 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, tafenoquine is an 8-aminoquinoline antimalarial, and its efficacy in malaria has been established. Any mechanistic link to smouldering systemic mastocytosis cannot be established from the data compiled for this report.
The TxGNN score is very high (99.05%), but it is a graph-based computational prediction only. Possible links to mast cell disease, such as effects on KIT-driven mast cell proliferation, oxidative stress, or lysosomal pathways, are speculative and not supported by any evidence gathered here. Malaria and smouldering systemic mastocytosis are also biologically very different diseases (a parasitic infection versus a clonal mast cell neoplasm), so the relationship between the original and new indication is not apparent.
Mechanistic validation, such as in vitro mast cell assays and KIT D816V models, would be required before any further consideration.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available.
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA210795 (Cancelled) | Krintafel (GlaxoSmithKline LLC) | Film-coated tablet | Not listed in the data compiled |
| NDA210607 (Cancelled) | Arakoda (60 Degrees Pharmaceuticals, Inc.) | Film-coated tablet | Not listed in the data compiled |
Both authorizations are oral tablets and both are marked as cancelled, so there is currently no valid US marketing license for single-ingredient tafenoquine in the data compiled.
Cytotoxicity
Not applicable. Tafenoquine is not an antineoplastic drug, and the predicted indication is a neoplasm for which no supporting evidence exists. This section is therefore omitted from the assessment.
Safety Considerations
- Drug Interactions: 21 interacting drugs were identified (all from the DDInter database).
- Major (5): Nitrous acid, Dofetilide, Prilocaine, Typhoid vaccine (live), and one further entry in the same category as listed in the interaction data.
- Moderate (16): including Metformin, Clofarabine, Dalfampridine, Guanfacine, Dapsone (systemic and topical), and several local anaesthetics (lidocaine, benzocaine, tetracaine, cocaine, proparacaine, oxybuprocaine, cinchocaine in topical, ophthalmic, or nasal forms).
Please refer to the package insert for warnings and contraindications, as these were not available in the data compiled for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction is supported only by a model score (Evidence Level L5), with no clinical trials, no literature, no mechanism of action data, and no clear biological connection between malaria and smouldering systemic mastocytosis. In addition, no US license for tafenoquine is currently valid, and label safety data are missing.
To proceed, the following is needed:
- Mechanism of action data for tafenoquine, and an analysis of any plausible link to mast cell biology
- Preclinical validation (in vitro mast cell assays, KIT D816V models)
- FDA package insert warnings and contraindications for a formal safety screening
- A literature and trial search specific to tafenoquine and mastocytosis
- Clarification of the regulatory and commercial status of the cancelled NDAs
- Review of the major drug interactions for relevance to the target patient population
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.