Entacapone
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Entacapone
- Entacapone: From Parkinson’s Disease Adjunct Therapy to PLA2G6-Associated Neurodegeneration
Entacapone: From Parkinson’s Disease Adjunct Therapy to PLA2G6-Associated Neurodegeneration
One-Sentence Summary
Entacapone is a COMT inhibitor, marketed in South Africa as part of the Stalevo levodopa/carbidopa/entacapone tablets. The registry data supplied did not record an original indication, so its use as a levodopa adjunct in Parkinson’s disease comes from general pharmacology. The TxGNN model predicts it may be useful for PLA2G6-associated neurodegeneration, but there are currently 0 clinical trials and 0 publications supporting this specific prediction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the SAHPRA data supplied (generally known as a levodopa adjunct in Parkinson’s disease) |
| Predicted New Indication | PLA2G6-associated neurodegeneration |
| TxGNN Prediction Score | 99.76% |
| Evidence Level | L5 (model prediction only) |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 2 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the Evidence Pack. Entacapone is generally known as a peripheral COMT inhibitor that prolongs the effect of levodopa. It is an established adjunct in Parkinson’s disease.
PLA2G6-associated neurodegeneration can include dystonia-parkinsonism, so a dopaminergic rationale is conceivable. However, the underlying defect lies in phospholipid metabolism and iron/synuclein pathology, which COMT inhibition does not address. The prediction most likely reflects proximity to Parkinson’s disease in the knowledge graph rather than a demonstrated mechanism. The link cannot be checked against known pharmacology until the original indication and mechanism data are completed.
Clinical Trial Evidence
Currently no related clinical trials registered for this predicted indication.
Literature Evidence
Currently no related literature available for this predicted indication.
Other Predicted Indications (Top 10)
Nine other candidates were predicted. Only two have any registered study or literature, and none has direct evidence of benefit.
| Rank | Predicted Indication | Score | Evidence Level | Notes |
|---|---|---|---|---|
| 4 | Paralysis agitans, juvenile, of Hunt | 99.60% | L5 | Early-onset parkinsonism. Mechanistic plausibility is higher than for most other candidates, but no juvenile-specific evidence exists. |
| 7 | Lewy body dementia | 99.25% | L4 | Indirect preclinical support only (PMID 23913715, in vitro antiparkinsonian agents and oligomer formation). The one registered trial (NCT04246437, Phase 1, recruiting, n=40) is an F-DOPA imaging study in autonomic failure, not a test of entacapone. Dopaminergic side effects such as psychosis and hallucinations are a particular concern in this population. |
| 10 | Progressive supranuclear palsy-corticobasal syndrome | 99.04% | L5 | Poor levodopa response makes the rationale weak. The one registered study (NCT02994719, N/A phase, recruiting, n=120) is a gait analysis with no entacapone intervention. |
| 2, 3, 5, 6, 8, 9 | Rasmussen encephalitis, myelitis, transaldolase deficiency, lethal infantile mitochondrial myopathy, fructose-1,6-bisphosphatase deficiency, perisylvian polymicrogyria syndrome | 99.06–99.73% | L5 | No plausible mechanistic path from COMT inhibition and no evidence found. |
South Africa Market Information
| Registration Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| Reg. No. 8/5.4.1/0138 | Stalevo 100/25 | Tablet | Not stated in the registry data supplied |
| Reg. No. 38/5.4.1/0137 | Stalevo 150/37.5 | Tablet | Not stated in the registry data supplied |
Both products are oral tablets.
Safety Considerations
Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.
No drug-interaction records were found in the query.
Conclusion and Next Steps
Decision: Hold
Rationale: The top prediction rests on a model score alone, with no trials or literature. The stated mechanism (COMT inhibition) does not address the disease pathology. The SAHPRA safety data is missing, which blocks safety screening.
To proceed, the following is needed:
- SAHPRA Professional Information (warnings and contraindications), which is a blocking gap
- Mechanism of action and original indication data (for example from DrugBank) to test the mechanistic link
- Clinical or preclinical evidence specific to PLA2G6-associated neurodegeneration
- If pursuing a better-supported candidate, a dedicated safety and evidence review for early-onset parkinsonism or Lewy body dementia, including psychiatric risk
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before any use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.