Spironolactone
| Evidence Level: L5 | Predicted Indications: 2 |
Table of Contents
- Spironolactone
- Spironolactone: From Hypertension and Heart Failure to Hypotrichosis Simplex of the Scalp
Spironolactone: From Hypertension and Heart Failure to Hypotrichosis Simplex of the Scalp
One-Sentence Summary
Spironolactone is an aldosterone receptor antagonist originally used for hypertension, congestive heart failure, and primary aldosteronism. The TxGNN model predicts it may be effective for hypotrichosis simplex of the scalp, but there are currently 0 clinical trials and 0 publications supporting this prediction, so it is a computational hypothesis only.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Hypertension, congestive heart failure, hyperaldosteronism / primary aldosteronism, Bartter disease, Waterhouse-Friderichsen syndrome |
| Predicted New Indication | Hypotrichosis simplex of the scalp |
| TxGNN Prediction Score | 99.26% |
| Evidence Level | L5 |
| US Market Status | Cancelled only (all licenses cancelled) |
| Number of NDAs | 8 (7 ANDAs and 1 NDA) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, spironolactone is an aldosterone receptor antagonist that also has anti-androgen activity (androgen receptor blockade and reduced androgen synthesis). This anti-androgen effect is the rationale for its off-label use in androgenetic alopecia and female pattern hair loss.
The link to the predicted indication is weak. Hypotrichosis simplex of the scalp is a rare hereditary hair loss disorder caused by variants in genes such as CDSN, APCDD1, and RPL21. These genes act through Wnt signaling and structural or ribosomal pathways, not through androgen-driven follicle miniaturization. The connection to spironolactone is therefore indirect and speculative.
The high TxGNN score (0.993) is a computational prediction only. A second prediction, congenital hypotrichosis milia (score 99.04%), likewise has no supporting trials or literature. It appears to be driven by the shared hair-loss phenotype, and no androgen-mediated mechanism has been established for it.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available.
US Market Information
All eight US authorizations are listed as cancelled, and no approved indication text was available for them.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ANDA202187 (NorthStar Rx) | Spironolactone | Tablet | Not available (cancelled) |
| ANDA040750 (Proficient Rx) | Spironolactone | Tablet, coated | Not available (cancelled) |
| ANDA205936 (RemedyRepack) | Spironolactone | Tablet, film coated | Not available (cancelled) |
| ANDA091426 (Amneal) | Spironolactone | Tablet | Not available (cancelled) |
| NDA209478 (Padagis) | Spironolactone | Suspension | Not available (cancelled) |
Safety Considerations
- Contraindication-related conditions (from the knowledge graph, not label text): kidney disease, anuria, pancreatitis, systemic lupus erythematosus (including pediatric), potassium deficiency disease, diabetes mellitus, diabetic ketoacidosis, hyperuricemia, gout, hyperparathyroidism, osteitis fibrosa, hypercalcemia, nephrocalcinosis, phosphorus metabolism disease, hepatic coma, hepatic encephalopathy, neonatal jaundice, pyoureter.
- Drug Interactions: 100 interactions were identified; the first 20 retrieved are summarized here.
- Major: loperamide.
- Moderate: hydrocortisone, triamcinolone, dexamethasone, betamethasone, budesonide, metformin, bupropion, morphine, bisacodyl, castor oil, dronabinol, exenatide, and the SGLT2 inhibitors canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin.
- Minor: doxycycline, acetylsalicylic acid, fidaxomicin.
Please refer to the package insert for full warnings and label contraindications, as these were not available for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests only on a model score. There are no clinical trials or publications, and the proposed mechanism (anti-androgen effect) does not fit the genetic, non-androgen-driven biology of this disorder. All US licenses are also cancelled.
To proceed, the following is needed:
- Mechanism of action data for spironolactone
- FDA package insert warnings and contraindications
- Evidence that links the genetic causes of hypotrichosis simplex (CDSN, APCDD1, RPL21) to a spironolactone-responsive pathway, such as preclinical or follicle model studies
- Any case reports, trials, or literature in this indication
- Route compatibility and similarity-to-original-indication assessments, which are still pending
- Clarification of current US marketing status, since all listed licenses are cancelled
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.