Isosorbide Dinitrate
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Isosorbide Dinitrate
- Pharmacist Assessment Report
- Isosorbide Dinitrate: From an Unspecified Licensed Indication to Alopecia (Top TxGNN Prediction)
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Canada Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Isosorbide Dinitrate: From an Unspecified Licensed Indication to Alopecia (Top TxGNN Prediction)
One-Sentence Summary
Isosorbide dinitrate (ISDN) is a nitric oxide (NO)-donating vasodilator. The licence records compiled for this report do not state an approved indication. The TxGNN model’s top-ranked prediction is alopecia, but it has 0 clinical trials and 0 publications, so it rests on model prediction alone. The best-supported direction among the model’s predictions is pulmonary hypertension (20 publications, no registered trials), which this report notes as a secondary finding.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the licence records |
| Predicted New Indication | Alopecia |
| TxGNN Prediction Score | 0.9999 |
| 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?
Currently, detailed mechanism of action data is not available in the compiled data. Based on general pharmacology, ISDN is an organic nitrate that releases nitric oxide, raising cGMP in smooth muscle and causing vasodilation.
For alopecia, one speculative hypothesis is that vasodilation could improve scalp perfusion around hair follicles, a mechanism shared with other vasodilators. No clinical trial or publication was found to support this, so it should be treated as a hypothesis only. The other hair-related predictions (congenital hypotrichosis milia, hypotrichosis simplex of the scalp, diffuse alopecia areata, hypertrichosis) are likewise prediction-only. For several of them, such as genetic hair disorders and autoimmune alopecia areata, the vasodilatory mechanism does not address the underlying cause.
Secondary finding: pulmonary hypertension
Among the other predictions, pulmonary hypertension (score 0.9998) has the most literature. Vasodilation by ISDN lowers pulmonary artery pressure and preload, which is mechanistically coherent. The retrieved studies are mostly small haemodynamic studies in COPD-associated pulmonary hypertension, end-stage cardiac disease and other settings, plus animal work. No registered trials were found. Reported concerns include possible ventilation/perfusion mismatch and a lack of long-term benefit data. For this disease the evidence level would be L3, but it is not the headline prediction of this report.
Clinical Trial Evidence
Currently no related clinical trials registered for alopecia.
For reference, trials retrieved under the broader prediction “vascular disease” (score 0.9997) are listed below. They do not study alopecia, and ISDN’s role in several is unclear.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02789033 | Phase 3 | Completed | 68 | ISDN spray plus chitosan in diabetic foot ulcers; results not provided |
| NCT00000478 | Phase 3 | Completed | Not reported | Pilot of treatment strategies for asymptomatic cardiac ischaemia |
| NCT00803634 | Phase 3 | Completed | 117 | Blood pressure control in acute heart failure (IV clevidipine vs standard care); ISDN role unverified |
| NCT01513070 | Phase 4 | Completed | 120 | Traditional-medicine formula vs ISDN in moderate coronary stenosis |
| NCT02135315 | NA | Completed | 1500 | Intensive vs standard blood pressure treatment in NSTE-ACS; ISDN not isolated |
Literature Evidence
Currently no related literature available for alopecia.
For reference, key publications retrieved for the pulmonary hypertension prediction (none concern alopecia):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39164577 | 2025 | Clinical study | Heart and Vessels | Bolus ISDN and its effects on pulmonary pressure and blood pressure in PH with cardiopulmonary comorbidities |
| 373940 | 1979 | Randomised, double-blind haemodynamic study | Clin Pharmacol Ther | Oral ISDN vs placebo in 18 COPD patients with pulmonary hypertension |
| 6423015 | 1984 | Haemodynamic study | Bull Eur Physiopathol Respir | Sublingual ISDN or nitroglycerin lowered pulmonary arterial pressure in COPD; only nitroglycerin reduced pulmonary vascular resistance |
| 3409916 | 1988 | Clinical study | Eur Heart J | Sustained haemodynamic improvement over two years in pulmonary hypertension from interstitial lung fibrosis (18 patients) |
| 2868878 | 1986 | Review | Drugs | Drug treatment of primary pulmonary hypertension, including ISDN among vasodilators |
| 7125407 | 1982 | Clinical study | Ann Intern Med | Vasodilators in primary pulmonary hypertension; ISDN was the only drug eliciting any reduction in pulmonary artery pressure |
| 28810603 | 2017 | Animal study | Exp Ther Med | Intratracheal ISDN improved pulmonary artery pressure in a rat heart-failure model |
| 2498122 | 1989 | Animal study | Exp Mol Pathol | ISDN compared with other agents in monocrotaline-induced pulmonary hypertension in rats |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 00441694 | ISDN | Not stated | Not stated |
| 00441686 | ISDN | Not stated | Not stated |
Safety Considerations
- Relations recorded in the knowledge graph (not label text): The TxGNN knowledge graph records contraindication relations with conditions including hypotensive disorder, hypertrophic cardiomyopathy, coronary artery disease, myocardial infarction, stroke and cerebrovascular disorders, intracerebral hemorrhage, intracranial hypertension, anaemias and hemoglobinopathy, and hyperthyroidism/Graves disease. These come from the graph, not from product labelling, and should be checked against the package insert.
- Drug Interactions: 100 interactions were found in the DDI database. Examples rated Moderate include bupropion, morphine, opium, dronabinol, nabilone, sapropterin, rosiglitazone, and the SGLT2 inhibitors canagliflozin, dapagliflozin, empagliflozin and ertugliflozin. Omeprazole is rated Minor.
- Other cautions from the literature: Nitrate tolerance develops quickly with continued use, and hypotension is a recognised risk of vasodilation, particularly in dialysis patients and those with low blood pressure.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The alopecia prediction has a very high model score but no clinical trials or publications, so it stays at L5. The mechanism is speculative, and the safety data compiled so far is incomplete (no label warnings or contraindications).
To proceed, the following is needed:
- Preclinical or early clinical evidence that ISDN affects hair growth or scalp perfusion, with consideration of topical delivery
- The Health Canada package insert warnings and contraindications
- Mechanism of action data from DrugBank
- The approved indication text for the two Canadian DINs
- A separate evaluation of pulmonary hypertension as a research question, since it has the most existing literature, though it is limited to small haemodynamic studies
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.