Sildenafil
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Sildenafil
- Sildenafil: From Erectile Dysfunction to Ambras Type Hypertrichosis Universalis Congenita
Sildenafil: From Erectile Dysfunction to Ambras Type Hypertrichosis Universalis Congenita
One-Sentence Summary
Sildenafil is a PDE5 inhibitor, widely known for treating erectile dysfunction (the SAHPRA data supplied do not state the registered indication). The TxGNN model predicts it may be effective for Ambras type hypertrichosis universalis congenita with a high score, but no clinical trials and no publications support this prediction, and the biology points the wrong way. Among the model’s other predictions, only genetic alopecia has early supporting evidence (2 trials, 1 publication).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the SAHPRA data supplied (generally erectile dysfunction) |
| Predicted New Indication | Ambras type hypertrichosis universalis congenita |
| TxGNN Prediction Score | 98.41% |
| Evidence Level | L5 (model prediction only) |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 4 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data are not available in the Evidence Pack. Sildenafil is a phosphodiesterase type 5 (PDE5) inhibitor. It raises intracellular cGMP, which causes vasodilation.
The top prediction is not convincing. Ambras syndrome is a rare genetic developmental condition, linked to rearrangements near the TRPS1 region, with no plausible PDE5 link. Sildenafil has also been reported to promote hair growth, so using it for a hair-excess disorder points in the opposite direction. The high score most likely reflects graph proximity (shared hair-phenotype nodes), not a therapeutic signal.
The same applies to the other high-scoring predictions: hypertrichosis, trichomegaly, congenital malformation syndromes, homozygous familial hypercholesterolaemia and hypoalphalipoproteinaemia. The pack found no clinical evidence and no mechanistic rationale for any of them.
Clinical Trial Evidence
Currently no related clinical trials registered for Ambras type hypertrichosis universalis congenita.
Literature Evidence
Currently no related literature available for Ambras type hypertrichosis universalis congenita.
Other Predicted Indication with Early Evidence: Genetic Alopecia (Rank 9)
This is the only prediction in the pack with supporting studies. Its TxGNN score is lower (75.03%), and its evidence level is L3 (Research Question, not a treatment recommendation). The mechanism is plausible: PDE5 inhibition raises cGMP, increases perifollicular blood flow, and may prolong the anagen (growth) phase. This is a minoxidil-like vascular effect.
| Source | Phase / Type | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT05369481 | NA | Unknown | 50 | Topical sildenafil 2% vs topical minoxidil 5% in male androgenetic alopecia. No results available. |
| NCT06527729 | Early Phase 1 | Completed | 28 | Sildenafil lipid nanocarrier in alopecia areata (an autoimmune, not genetic, alopecia). Supports feasibility of topical use only. |
| PMID 30292404 | 2018, laboratory study | n/a | n/a | Reports a novel hair-growth effect of sildenafil on human hair follicles (Biochem Biophys Res Commun). |
These studies are small and early, come mostly from a single site, and mostly use topical formulations. Efficacy versus minoxidil and long-term safety are not established.
South Africa Market Information
Sildenafil has 4 SAHPRA registrations. Approved indication text and manufacturer are not included in the supplied data.
| Registration Number | Product Name | Dosage Form |
|---|---|---|
| Reg. No. 42/7.1.5/1071 | Dynafil | Tablet |
| Reg. No. 50/7.1.5/0062 | Lifaned 50 | Film-coated tablet |
| Reg. No. 43/7.1.5/0887 | Avigra | Tablet |
| Reg. No. 45/7.1.5/0874 | Raviag | Tablet |
All registered products are oral. No topical sildenafil product is registered, so any hair-loss use would require a new formulation.
Safety Considerations
Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.
As general background not drawn from the Evidence Pack: PDE5 inhibitors are contraindicated with nitrates, so the PI must be checked before any use.
Conclusion and Next Steps
Decision: Hold
Rationale: The top prediction (Ambras type hypertrichosis universalis congenita) rests on a graph score alone (L5). It has no trials or publications, and sildenafil’s hair-promoting effect makes benefit unlikely. Genetic alopecia is the only prediction worth following up, as a research question.
To proceed, the following is needed:
- SAHPRA Professional Information (warnings, contraindications, approved indications) to complete safety screening
- Mechanism-of-action data from DrugBank
- For genetic alopecia: a larger randomised trial of topical sildenafil against minoxidil with reported results, plus topical safety data
- A topical formulation and route-compatibility assessment, since no topical product is registered in South Africa
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before any clinical use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.