Phentolamine
| Evidence Level: L5 | Predicted Indications: 9 |
Table of Contents
Phentolamine: Visceral calciphylaxis
One-Sentence Summary
Phentolamine is an alpha-adrenergic blocker originally used for pheochromocytoma-related hypertensive crises and peripheral vascular disease. The TxGNN model predicts it may be effective for visceral calciphylaxis, but there are currently no clinical trials and no publications supporting this specific prediction. The evidence is model prediction only.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Visceral calciphylaxis |
| TxGNN Prediction Score | 1.0000 |
| Evidence Level | L5 |
| Canada Market Status | Marketed (marketed DINs: 2 of 2) |
| Number of DINs | 2 (marketed: 2) |
| 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 pharmacology, phentolamine is a non-selective alpha-adrenergic antagonist that causes vasodilation. Its efficacy in pheochromocytoma-related hypertensive crises and in peripheral vascular disease is well established.
Visceral calciphylaxis (calcific uremic arteriolopathy) involves microvascular occlusion and ischaemia. This gives a theoretical link to a vasodilator. However, the disease is driven mainly by mineral metabolism disturbance, vascular calcification and thrombosis, so alpha-blockade is not a recognised mechanism for treating it. The high model score is not matched by any trial or publication, and the prediction should be treated as a hypothesis only.
Clinical Trial Evidence
Currently no related clinical trials registered for visceral calciphylaxis.
The following trials were returned, none of which tests phentolamine as a treatment for the predicted calciphylaxis indication. They are shown only as background:
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT06286059 | Phase 2/3 | Unknown | 60 | Phentolamine to prevent contrast-associated acute kidney injury after complex PCI in high-risk patients |
| NCT05997732 | Phase 4 | Recruiting | 30 | Sex differences in sympathetic neurovascular transduction and adrenergic receptor role |
| NCT05219799 | Early Phase 1 | Recruiting | 72 | Sex differences in hypoxic vasodilation and the impact of obesity |
| NCT05525416 | NA | Completed | 17 | Sex differences in sympathetic vascular reactivity at high altitude |
The large stroke blood-pressure trials matched to this term (NCT01422616, NCT00716079, NCT00226096) do not appear to test phentolamine and are not counted as evidence.
Literature Evidence
Currently no related literature available for visceral calciphylaxis.
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02243737 | Phentolamine Mesylate Injection Sandoz Standard | Not specified | Not specified |
| 02421666 | Oraverse | Not specified | Not specified |
Safety Considerations
- Disease contraindications (from the knowledge graph, not label text): liver disease, gallbladder disease, hypotensive disorders, coronary artery disease, myocardial infarction, coronary thrombosis, haemoglobinopathy, sudden cardiac arrest, heart conduction disease, glaucoma, atrioventricular block.
- Drug Interactions: 100 interactions were identified. Moderate-level interactions include bupropion, morphine, dronabinol and the SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin). Minor-level interactions include many insulin products (human, aspart, degludec, detemir, glargine, glulisine, lispro and others).
Please refer to the package insert for the official warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale:
- The prediction score is very high, but there are no trials or publications for visceral calciphylaxis, and the proposed mechanism (alpha-blockade) does not address the main drivers of the disease. The evidence is L5, model prediction only.
To proceed, the following is needed:
- Health Canada package insert warnings and contraindications, which are required for safety screening
- Detailed mechanism of action data
- Preclinical or case-level evidence of phentolamine in calcific uremic arteriolopathy
- An assessment of hypotension risk in patients with renal failure
- Confirmation of the approved indications and dosage forms for the two Canadian DINs
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.