Nitroglycerin
| Evidence Level: L3 | Predicted Indications: 4 |
Table of Contents
- Nitroglycerin
- Pharmacist Assessment Report
- Nitroglycerin: From an Unspecified Original Indication to Pulmonary Hypertension
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Australia Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Nitroglycerin: From an Unspecified Original Indication to Pulmonary Hypertension
One-Sentence Summary
Nitroglycerin is a nitric oxide donor vasodilator. It is registered in Australia as a transdermal patch (Transiderm-Nitro 25), but the data compiled for this report contain no approved indication text. The TxGNN model predicts it may be effective for pulmonary hypertension, with 3 clinical trials and 20 publications currently linked to this direction. The evidence is mostly small, early-phase or older haemodynamic studies, so it supports further research rather than a clinical change.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the data compiled for this report (the ARTG entry has no indication text) |
| Predicted New Indication | Pulmonary hypertension |
| TxGNN Prediction Score | 0.9961 |
| Evidence Level | L3 |
| 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?
Detailed mechanism of action data is not available in the compiled data. Based on established pharmacology, nitroglycerin is a nitric oxide (NO) donor. NO activates soluble guanylate cyclase and raises cGMP in vascular smooth muscle, causing vasodilation.
Pulmonary hypertension involves persistent pulmonary vasoconstriction and vascular remodelling. A vasodilator acting through the NO–cGMP pathway is therefore biologically plausible. Delivery by inhalation or nebulisation may give relatively selective pulmonary vasodilation and limit systemic hypotension. Early haemodynamic studies in pulmonary hypertension, including COPD-associated disease, point in the same direction.
The original indication is not recorded in the compiled data, so the relationship between the original and new indications cannot be assessed directly. The available trials focus on acute vasoreactivity testing or perioperative and neonatal adjunct use, not long-term disease modification. Note also that the trials use nebulised or inhaled nitroglycerin, whereas the registered Australian product is a transdermal patch.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT07214129 | Not applicable | Completed | 20 | Nebulised nitroglycerin as a vasoreactive agent in pulmonary arterial hypertension; a vasoreactivity test, not a therapeutic outcome trial |
| NCT04594629 | Phase 1 | Unknown | 120 | Nebulised epoprostenol (PGI2) vs nebulised nitroglycerin for pulmonary hypertension after valve replacement surgery; randomised, but status unknown so data reliability is uncertain |
| NCT07603037 | Not applicable | Not yet recruiting | 12 | Nicardipine and nitroglycerin effects on ventilation-perfusion ratio in acute respiratory failure with hypertension; only indirectly related |
No ANZCTR trial identifiers were found in the compiled data.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 40888971 | 2025 | RCT | Eur J Pediatr | Nebulised nitroglycerin as an adjunct in 80 newborns with persistent pulmonary hypertension; assessed echocardiographic and clinical parameters |
| 29880427 | 2018 | RCT | J Cardiothorac Vasc Anesth | Dobutamine and nitroglycerin vs milrinone for perioperative pulmonary hypertension in mitral valve surgery |
| 34082850 | 2021 | Review/cohort | Cardiol Young | Inhaled nitroglycerin for acute pulmonary arterial hypertension in children with congenital heart disease |
| 16707530 | 2006 | Clinical study | Br J Anaesth | Acute effects of inhaled nitroglycerin on pulmonary and systemic haemodynamics in children with congenital heart disease |
| 3096761 | 1986 | Clinical study | Eur J Respir Dis Suppl | Transdermal nitroglycerin lowered pulmonary artery pressure within 24 hours, with the effect maintained at 4 weeks |
| 6407380 | 1983 | Haemodynamic study | Ann Intern Med | In 9 patients with chronic pulmonary hypertension, nitroglycerin raised cardiac index and lowered pulmonary vascular resistance by about 40% |
| 6423015 | 1984 | Haemodynamic study | Bull Eur Physiopathol Respir | In COPD-related pulmonary hypertension, nitroglycerin reduced pulmonary vascular resistance |
| 39059783 | 2024 | Review | Curr Probl Cardiol | Advances in nebulised inhalation therapy for pulmonary arterial hypertension |
| 42572609 | 2026 | Review | JHLT Open | Perioperative use of inhaled pulmonary vasodilators; notes nitroglycerin lacks pulmonary selectivity |
| 26139748 | 2015 | Review | Ann Card Anaesth | Inhaled therapy for perioperative pulmonary hypertension |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 13490B | Transiderm-Nitro 25 | Transdermal patch 25 mg | Not stated in the data compiled for this report |
Safety Considerations
- Disease-level cautions from the knowledge graph (not label text): the TxGNN knowledge graph links nitroglycerin to contraindication or caution with hypotensive disorder, hypertrophic cardiomyopathy, methaemoglobinaemia, sulfhaemoglobinaemia, anaemia, macrocytic anaemia, intracerebral haemorrhage, constrictive pericarditis, restrictive cardiomyopathy and cardiac tamponade.
- Drug Interactions: 228 interactions were identified. Moderate-level examples include bupropion, morphine, canagliflozin, dapagliflozin, empagliflozin, dronabinol, nabilone, rosiglitazone and sapropterin. Minor-level examples include aspirin, atropine, hyoscyamine, glycopyrronium, scopolamine and omeprazole.
- Systemic vasodilation carries a risk of hypotension, which is particularly relevant in right ventricular dysfunction or perioperative settings.
Please refer to the TGA-approved Product Information (PI) for label warnings and contraindications, as these were not available in the compiled data.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction is mechanistically plausible and the TxGNN score is high. However, the supporting trials are small, early-phase or non-phased, with no Phase 2 or 3 RCT, and they use nebulised or inhaled delivery rather than the registered transdermal patch. The original indication is also unknown, so novelty cannot be confirmed. This is best treated as a research question.
To proceed, the following is needed:
- The TGA-approved Product Information, including indications, warnings and contraindications
- Mechanism of action data confirmed from DrugBank
- Adequately powered Phase 2/3 RCTs with clinical outcomes, not only acute vasoreactivity
- Evaluation of the formulation and route (nebulised or inhaled vs transdermal) and whether a suitable product is available in Australia
- A safety plan addressing hypotension and right ventricular function in pulmonary hypertension patients
Other lower-ranked predictions (kyphoscoliotic heart disease, Prinzmetal angina, primary hereditary glaucoma, congenital hypotrichosis milia) were reviewed. None has supporting trial evidence, and for Prinzmetal angina the use appears to be already established rather than new, so none is recommended for advancement at this stage.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.