Artemether
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Artemether: From Malaria Treatment to Acquired Angioedema
One-Sentence Summary
Artemether is an artemisinin-derivative antimalarial, registered in South Africa as part of the combination product Coartem (artemether-lumefantrine). The TxGNN model ranks acquired angioedema as its top predicted new indication, but no clinical trials and no publications support this prediction, so it is a graph-based signal only. The highest-evidence predictions for this drug are the malaria indications (ranks 2 and 3), which are its established use and not true repurposing.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the SAHPRA registration data; artemether is an antimalarial (Coartem) |
| Predicted New Indication | Acquired angioedema |
| TxGNN Prediction Score | 99.90% |
| Evidence Level | L5 |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the evidence pack. Artemether is an artemisinin derivative whose endoperoxide bridge is thought to generate free radicals that kill Plasmodium parasites. It is used with lumefantrine as artemether-lumefantrine (AL).
Acquired angioedema is driven by bradykinin and complement pathways. There is no documented link between these pathways and artemether’s antiparasitic mechanism. The very high score (0.999) most likely reflects the model’s knowledge-graph neighbourhood, not a biological rationale. The same applies to the other angioedema predictions (angioedema, hereditary angioedema, RAAS-blocker-induced angioedema), which share this pattern.
The evidence pack rates all of these non-malaria predictions L5 with a Hold recommendation, including nephrogenic syndrome of inappropriate antidiuresis, acute contagious conjunctivitis, conjunctivitis and scleroderma. None has trials or literature behind it.
Clinical Trial Evidence
Currently no related clinical trials registered for acquired angioedema.
Literature Evidence
Currently no related literature available for acquired angioedema.
Supporting Evidence for the Established Malaria Indications (Ranks 2–3)
These are not evidence for the primary prediction. They are shown because they are the only substantial evidence in this pack for artemether.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT05842954 | Phase 3 | Completed | 1720 | KLU156 (ganaplacide + lumefantrine-SDF) vs Coartem in uncomplicated P. falciparum malaria; AL is the comparator |
| NCT00344006 | Phase 3 | Completed | 1395 | Chlorproguanil-dapsone-artesunate vs artemether-lumefantrine in African children and adolescents |
| NCT00316329 | Phase 3 | Completed | 1032 | Artesunate-amodiaquine (1 or 2 intakes a day) vs Coartem, non-inferiority at day 28 |
| NCT01845701 | Phase 3 | Completed | 720 | Artesunate-amodiaquine and dihydroartemisinin-piperaquine vs AL over 42 days in Cameroon |
| NCT01916954 | Phase 3 | Completed | 96 | Two AL regimens in pregnant women with uncomplicated P. falciparum malaria, DRC |
| NCT00885287 | Phase 4 | Completed | 830 | AL efficacy, safety and PK interaction with nevirapine-based ART in HIV-infected patients, Tanzania |
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31210357 | 2019 | Cochrane systematic review | Cochrane Database Syst Rev | Intramuscular artemether compared with quinine and artesunate in severe malaria |
| 22548983 | 2012 | Systematic review | Malar J | Safety and efficacy of AL for uncomplicated P. falciparum malaria in pregnancy |
| 37979594 | 2023 | RCT | Lancet | PRIMA: primaquine radical cure in P. falciparum malaria in areas co-endemic with P. vivax |
| 38705163 | 2024 | Phase 2 RCT | Lancet Microbe | AL with or without single-dose primaquine, effect on gametocyte carriage and transmission, Mali |
| 40138574 | 2025 | Molecular study | J Infect Dis | AL treatment selects pfmdr1 increased copy number in African infections; reduced AL efficacy is emerging in Africa |
The evidence is for the fixed-dose combination with lumefantrine, not artemether alone.
South Africa Market Information
| Registration Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| Reg. No. 34/20.2.6 /0161 | Coartem | Tablet (oral) | Not provided in the registration data |
Safety Considerations
Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.
Two points from the supporting malaria trials are relevant to AL use:
- Antiretroviral co-treatment can change antimalarial exposure. One example is the efavirenz interaction studied in NCT04708496.
- Artemisinin-resistance surveillance is needed.
Conclusion and Next Steps
Decision: Hold
Rationale: Acquired angioedema is a model-only prediction at L5. It has no trials, no literature and no plausible mechanistic link to artemether. The malaria predictions are well supported (L1), but they are artemether’s established use and not repurposing.
To proceed, the following is needed:
- A targeted literature search on artemisinins and bradykinin or complement-mediated disease, to test whether any rationale exists
- Detailed mechanism of action data (MOA) from DrugBank
- SAHPRA Professional Information (warnings and contraindications), which is currently missing and blocks safety screening
- Confirmation of the approved indication text for the Coartem registration
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.