Isosorbide Mononitrate

Evidence Level: L5

Predicted Indications: 10

Isosorbide Mononitrate

Pharmacist Assessment Report

Isosorbide Mononitrate: From an Unspecified Original Indication to hypertrichosis (disease)

One-Sentence Summary

Isosorbide mononitrate is a nitric oxide (NO) donor and vasodilator. The data compiled for this report do not state its approved indication in Australia. The TxGNN model predicts it may be effective for hypertrichosis (disease), with a very high score, but no clinical trials and no publications currently support this prediction. The only candidate with any related literature is pulmonary arterial hypertension (rank 10), and that evidence is indirect.

Quick Overview

Item	Content
Original Indication	Not available in the data compiled for this report (the approved indication text on the ARTG entry is blank)
Predicted New Indication	Hypertrichosis (disease)
TxGNN Prediction Score	1.0000
Evidence Level	L5
Australia Market Status	Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data
Number of PBS Items	1 (valid: 1)
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, isosorbide mononitrate is an NO donor. It raises cyclic GMP (cGMP) in vascular smooth muscle and causes vasodilation.

For hypertrichosis, no plausible mechanistic link has been identified. NO-mediated vasodilation has been loosely discussed in hair follicle biology, as with minoxidil, but this is speculative. The high score comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence. It is not backed by clinical or literature data.

The other top-ranked predictions (Ambras-type hypertrichosis, hair shaft abnormalities, hypotrichosis, alopecia and alopecia areata, and several malformation syndromes) show the same pattern. Their scores come from the TxGNN model (deep learning) and may reflect similarities the model learned between related hair and ectodermal diseases, not biological evidence. Most are genetic or structural conditions that a vasodilator would not be expected to correct. The only biologically plausible candidate is pulmonary arterial hypertension (PAH), ranked 10th (score 0.9994). The NO-sGC-cGMP pathway is a validated PAH target (PDE5 inhibitors, riociguat). However, organic nitrates are not established in PAH, and concerns include tolerance, systemic hypotension and possible ventilation-perfusion mismatch.

Clinical Trial Evidence

Currently no related clinical trials registered (for hypertrichosis or for the other predicted indications).

Literature Evidence

Currently no related literature available for hypertrichosis.

For reference, the two indirect publications found for the PAH prediction (rank 10) are:

PMID	Year	Type	Journal	Key Findings
16422873	2005	Clinical hemodynamic study	J Sex Med	Haemodynamic effects of sildenafil combined with isosorbide mononitrate in men with coronary artery disease and erectile dysfunction (not a PAH population)
29705351	2018	Preclinical (rat)	Life Sci	Stimulation of NO-sensitive soluble guanylate cyclase in monocrotaline-induced pulmonary hypertensive rats (did not test isosorbide mononitrate)

Australia Market Information

ARTG Number	Product Name	Dosage Form	Approved Indication
ARTG 13461L	Imdur Durule	Tablet 60 mg (sustained release), oral	Not stated in the data compiled

Safety Considerations

Disease associations flagged in the knowledge graph (not label text): hypotensive disorder, hypertrophic cardiomyopathy, myocardial infarction, coronary thrombosis, haemoglobinopathy, anaemia (including macrocytic), hyperthyroidism, Graves disease, thyrotoxicosis and intracerebral haemorrhage. These come from graph contraindication edges and need confirmation against the Product Information.
Drug interactions: 100 interactions were identified. Examples rated Moderate include bupropion, morphine, opium, dronabinol, nabilone, sapropterin, rosiglitazone and the SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin). Omeprazole is rated Minor. Several others (e.g. calcitriol, pantoprazole, glimepiride, metformin) have an unknown severity rating.
General concern for any non-cardiac use: systemic nitrate dosing carries risks of hypotension and headache. These would be hard to justify for a cosmetic or dermatological indication.

Please refer to the TGA-approved Product Information (PI) for the full warnings and contraindications, which were not available for this report.

Conclusion and Next Steps

Decision: Hold

Rationale: The prediction rests on a TxGNN model (deep learning) score alone (Evidence Level L5), with no registered trials, no relevant publications and no credible mechanism for hypertrichosis. The only plausible candidate, PAH, has just indirect, low-tier evidence and is better treated as a research question than as a repurposing recommendation.

To proceed, the following is needed:

The approved indication text from the TGA PI/ARTG entry, to confirm the original indication
Mechanism of action data (e.g. from DrugBank)
The PI warnings and contraindications, to complete safety screening
For PAH, a focused literature review and, if justified, preclinical or early-phase haemodynamic studies addressing tolerance, hypotension and gas exchange
No further work on hypertrichosis or the other hair/malformation predictions unless a credible mechanism emerges
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.