Propranolol
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Propranolol: From Hypertension and Cardiac Disorders to Distal Myopathy, Tateyama Type
One-Sentence Summary
Propranolol is a non-selective beta-blocker, originally used for hypertension, arrhythmias, hypertrophic cardiomyopathy and infantile hemangioma. The TxGNN model's top-ranked prediction is distal myopathy, Tateyama type, but this is a model prediction only, with 0 clinical trials and 0 publications supporting it. Better-supported candidates lower in the ranking are intramuscular hemangioma (about 20 publications, indirect evidence from infantile hemangioma) and cardiomyopathy (about 20 publications, mostly older studies in hypertrophic cardiomyopathy).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Hypertension, atrial fibrillation, hypertrophic cardiomyopathy, hemangioma (indications from the knowledge graph; Singapore licence indication text is not available) |
| Predicted New Indication | Distal myopathy, Tateyama type |
| TxGNN Prediction Score | 99.40% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 8 |
| 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 known information, propranolol is a non-selective beta-adrenergic blocker. It lowers heart rate and myocardial oxygen demand, and has anti-angiogenic and vasoconstrictive effects in hemangioma. Its efficacy in cardiovascular conditions and infantile hemangioma is well established.
For distal myopathy, Tateyama type (a rare caveolin-3-related muscle disease), no plausible beta-adrenergic mechanism is evident. The high score of 0.994 appears to reflect graph-based proximity only. The same applies to the second-ranked prediction, congenital myopathy with excess of thin filaments.
Other candidates in the top 10 are more biologically plausible:
- Intramuscular hemangioma, breast epithelioid hemangioma and breast capillary hemangioma share the hemangioma mechanism. Propranolol is first-line therapy for infantile hemangioma, but intramuscular hemangioma is a typically non-involuting lesion, and the breast entities are distinct from infantile hemangioma. Evidence therefore does not transfer directly.
- Cardiomyopathy is largely an extension of the existing hypertrophic cardiomyopathy indication rather than true repurposing.
- Cirrhotic cardiomyopathy has mixed signals. One 2024 report suggests propranolol may correct prolonged QT, while 2020–2022 reports show blunted cardiovascular effects and possible circulatory and renal harm in advanced disease.
Clinical Trial Evidence
Currently no related clinical trials registered for the top-ranked prediction, or for any of the top 10 predictions.
Literature Evidence
Currently no related literature available for distal myopathy, Tateyama type. The table below shows the most relevant publications for the best-supported candidate, intramuscular hemangioma (rank 7). All concern infantile hemangioma rather than the intramuscular subtype.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 35466712 | 2023 | Systematic review / meta-analysis | Ann Otol Rhinol Laryngol | Propranolol versus atenolol for infantile hemangioma; asks whether propranolol should remain the gold standard |
| 23266923 | 2013 | Consensus report | Pediatrics | Consensus on initiating and using propranolol for infantile hemangioma, including safety monitoring and dose escalation |
| 34719577 | 2022 | Randomized, double-blind study | Biol Pharm Bull | Propranolol gel (1% or 5%) versus placebo for infantile hemangioma over 24 weeks |
| 36243426 | 2022 | Review | Dermatol Clin | Systemic propranolol is a crucial element in infantile hemangioma management |
| 32662682 | 2020 | Review | Expert Rev Clin Pharmacol | Propranolol is the mainstay for problematic proliferating infantile hemangioma; alternatives explored |
| 28833230 | 2017 | Literature review | Laryngoscope | Efficacy and rebound rates of propranolol in subglottic hemangioma |
| 25962208 | 2015 | Safety review | Pediatr Endocrinol Rev | Propranolol-induced hypoglycemia in infantile hemangioma treatment, with prevention guidance |
| 38739176 | 2024 | Clinical study (design unverified) | Front Pharmacol | Propranolol may correct prolonged QT intervals in cirrhosis (relevant to cirrhotic cardiomyopathy, rank 5) |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN00076P | INPANOL TABLETS 10 mg | Tablet | Not available |
| SIN07707P | NALOL TABLET 10 mg (Revised formula) | Tablet | Not available |
| SIN01621P | PROPANOL TABLETS 40 mg | Film-coated tablet | Not available |
| SIN01978P | NALOL TABLET 40 mg | Tablet | Not available |
| SIN07708P | NALOL TABLET 80 mg | Tablet | Not available |
Three further registrations (APO-PROPRANOLOL 10 mg and 40 mg, PROPANOL 10 mg) are also valid, giving 8 valid single-ingredient licences in total. All are oral tablets.
Safety Considerations
Contraindications flagged in the knowledge graph (disease-level associations, not package insert text), including:
- Respiratory and metabolic: bronchitis, diabetes mellitus, diabetic ketoacidosis, gout, potassium deficiency
- Organ disease: kidney disease, liver disease, hepatic encephalopathy and coma, pancreatitis, gallbladder disease, anuria
- Neuromuscular: myasthenia gravis, myopathy, muscular disease, familial periodic paralysis
- Other: systemic lupus erythematosus, anxiety disorder, hyperparathyroidism, hypercalcemia
Of particular note, the knowledge graph lists myopathy and muscular disease as contraindications. This runs against the model's top predictions (distal myopathy and congenital myopathy).
Drug interactions (100 recorded; examples shown):
- Major: Epinephrine
- Moderate: corticosteroids (hydrocortisone, dexamethasone, betamethasone, budesonide, triamcinolone), anticholinergics (atropine, hyoscyamine, methscopolamine), bupropion, morphine, cimetidine, canagliflozin, chlorpropamide, lorcaserin
- Minor: aspirin, ascorbic acid, magnesium oxide
Literature also notes hypoglycemia as an adverse effect in infants treated for hemangioma, and possible harm to circulatory and renal function in cirrhosis with refractory ascites.
Please refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The top-ranked prediction, distal myopathy, Tateyama type, is supported only by a graph-based score, with no trials, no literature and no plausible mechanism. The knowledge graph also lists myopathy as a contraindication. Propranolol is widely marketed in Singapore (8 valid licences), but the better-supported candidates (intramuscular hemangioma, cardiomyopathy) rely on indirect evidence or extend existing indications, so they are better treated as research questions than as new-indication opportunities.
To proceed, the following is needed:
- Package insert warnings and contraindications from the Health Sciences Authority (HSA) website, and approved indication text for the Singapore licences
- Mechanism-of-action data from DrugBank
- For intramuscular hemangioma: direct evidence in that subtype, such as case series or a registered trial
- For cirrhotic cardiomyopathy: controlled studies resolving the conflicting benefit-risk signals
- Review of the knowledge-graph contraindication against any myopathy indication before further work
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.