Sildenafil
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Sildenafil
- Sildenafil: From Pulmonary Arterial Hypertension and Erectile Dysfunction to Ambras Type Hypertrichosis Universalis Congenita
Sildenafil: From Pulmonary Arterial Hypertension and Erectile Dysfunction to Ambras Type Hypertrichosis Universalis Congenita
One-Sentence Summary
Sildenafil is a PDE5 inhibitor originally used for pulmonary arterial hypertension, erectile dysfunction, psychologic dyspareunia and premature ejaculation. The TxGNN model predicts it may be effective for Ambras type hypertrichosis universalis congenita, but there are 0 clinical trials and 0 publications supporting this prediction, so it is a model prediction only. Among the other top-10 predictions, genetic alopecia has the most (still preliminary) support: a single 2018 publication on sildenafil and hair growth.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Pulmonary arterial hypertension; erectile dysfunction; psychologic dyspareunia; premature ejaculation (the Singapore licence records contain no approved-indication text) |
| Predicted New Indication | Ambras type hypertrichosis universalis congenita |
| TxGNN Prediction Score | 98.41% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 20 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on general knowledge, sildenafil inhibits phosphodiesterase type 5 (PDE5), which raises intracellular cGMP and causes vasodilation. This underlies its efficacy in pulmonary arterial hypertension and erectile dysfunction.
The link to Ambras syndrome is weak. One hypothesis is that raised cGMP could affect hair follicle blood supply and signalling. However, Ambras-type hypertrichosis is driven by genetic and developmental dysregulation of hair growth. There is no established rationale for benefit, and sildenafil could plausibly worsen hair overgrowth rather than treat it. The high score should be read as a knowledge-graph prediction, not as evidence of efficacy.
For context, none of the other top-10 predictions has clinical trial support either. Of these, genetic alopecia (rank 9, score 75.0%) is the only one with a directly relevant publication: a 2018 paper reporting a novel effect of sildenafil on hair growth in human hair follicles. It is rated L4 and labelled a research question. Its study type is not specified, so it should be treated as preliminary.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
For the top-ranked prediction (Ambras type hypertrichosis universalis congenita), currently no related literature is available.
For reference, the literature found for other predicted indications:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 30292404 | 2018 | Unspecified (likely preclinical or observational) | Biochem Biophys Res Commun | Investigates the effect of sildenafil on human hair follicles. Linked to genetic alopecia (rank 9). |
| 31175705 | 2019 | Case report | Am J Med Genet A | Glibenclamide treatment in a neonate with Cantú syndrome (ABCC9 gain-of-function variant). Does not involve sildenafil. Linked to hypertrichosis (rank 5). |
Singapore Market Information
There are 20 valid single-ingredient licences. Five main ones are shown. The licence records contain no approved-indication text.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN10805P | VIAGRA TABLET 50 mg | Film-coated tablet | Not stated in the records |
| SIN10804P | VIAGRA TABLET 25 mg | Film-coated tablet | Not stated in the records |
| SIN10806P | VIAGRA TABLET 100 mg | Film-coated tablet | Not stated in the records |
| SIN13244P | Revatio Film-Coated Tablets 20mg | Film-coated tablet | Not stated in the records |
| SIN16024P | SILCAP® 50 CAPSULE 50MG | Capsule | Not stated in the records |
Safety Considerations
Package insert warnings and contraindications were not available, so please refer to the package insert for them.
- Contraindication-related conditions (knowledge graph, not label text): The knowledge graph links sildenafil with caution or contraindication in conditions including liver failure, aortic stenosis, hypotensive disorder, acute coronary syndrome, myocardial infarction, stroke and cerebrovascular disorders, hypertrophic cardiomyopathy, sickle cell anaemia and other haemoglobinopathies, plasma cell myeloma, leukaemia, priapism, Peyronie disease, anterior ischaemic optic neuropathy, hearing loss disorders, oesophageal dyskinesia and pulmonary veno-occlusive disease.
- Drug Interactions: 100 interactions were identified. The only major one among those listed is clarithromycin. Moderate interactions include aprepitant, morphine, dexamethasone, cimetidine, miconazole, clotrimazole, papaverine, opium, lorcaserin and several SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin).
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction for Ambras-type hypertrichosis rests on model score alone, with no trials or literature, and there is no credible mechanism for benefit (possible worsening of hair overgrowth). The wider top-10 list is also entirely L5 apart from genetic alopecia (L4, a research question).
To proceed, the following is needed:
- Package insert warnings and contraindications (from the HSA website)
- Mechanism of action data (from DrugBank)
- For genetic alopecia: review of the full text of PMID 30292404 to establish study type, followed by controlled human studies
- Specialist clinical review before any further work on Ambras syndrome, including whether the safety profile is acceptable in this population
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.