Nitroglycerin
| Evidence Level: L3 | Predicted Indications: 5 |
Table of Contents
Nitroglycerin: From Angina and Vasodilator Therapy to Pulmonary Hypertension
One-Sentence Summary
Nitroglycerin is a nitric oxide (NO) donor and vasodilator. The New Zealand licence records compiled for this report do not state an approved indication, but the product forms (ointment, patches, sublingual spray) are consistent with cardiovascular and anal-fissure use. The TxGNN model predicts it may be effective for pulmonary hypertension, with 3 clinical trials (1 completed, small, non-phased) and 20 publications (mostly reviews and small haemodynamic studies, plus one randomised trial in newborns) supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the available licence records |
| Predicted New Indication | Pulmonary hypertension |
| TxGNN Prediction Score | 99.61% |
| Evidence Level | L3 |
| New Zealand Market Status | Cancelled only (no currently valid licences) |
| Number of Authorizations | 4 (all cancelled) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the compiled data. Based on known pharmacology, nitroglycerin is an NO donor: NO activates soluble guanylate cyclase, raises cGMP and relaxes vascular smooth muscle. This pathway is the same one targeted by established pulmonary hypertension therapies.
Its established use as a vasodilator is mechanistically close to the new indication, since lowering pulmonary vascular resistance is the therapeutic goal. Given by nebulisation or inhalation, it may produce relatively selective pulmonary vasodilation with less systemic hypotension. Older haemodynamic studies (1983–1984) and recent paediatric and neonatal reports (2021, 2025) show acute vasodilatory effects. Durable clinical benefit has not been demonstrated.
The evidence level of L3 reflects the mix of reviews, haemodynamic studies and small trials. No completed Phase 3 RCTs exist.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT07214129 | Not applicable | Completed | 20 | Nebulised nitroglycerin as a vasoreactivity agent in pulmonary arterial hypertension; supports feasibility and acute haemodynamics only |
| NCT04594629 | Phase 1 | Unknown | 120 | Nebulised PGI2 vs nebulised nitroglycerin for pulmonary hypertension after valve replacement surgery; results unverified |
| NCT07603037 | Not applicable | Not yet recruiting | 12 | Nicardipine and nitroglycerin effects on ventilation-perfusion in acute respiratory failure; physiological pilot, indirectly relevant |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 40888971 | 2025 | RCT | Eur J Pediatr | Nebulised nitroglycerin as adjuvant in 80 newborns with persistent pulmonary hypertension; echocardiographic and clinical parameters assessed |
| 29880427 | 2018 | RCT | J Cardiothorac Vasc Anesth | Dobutamine plus nitroglycerin vs milrinone for perioperative pulmonary hypertension in mitral valve surgery |
| 34082850 | 2021 | Clinical study / review | Cardiol Young | Inhaled nitroglycerin for acute treatment of PAH 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 PAH |
| 6407380 | 1983 | Haemodynamic study | Ann Intern Med | In 9 patients, nitroglycerin reduced pulmonary vascular resistance by about 40% and increased cardiac index |
| 6423015 | 1984 | Haemodynamic study | Bull Eur Physiopathol Respir | Nitroglycerin lowered pulmonary pressure and vascular resistance in COPD-related pulmonary hypertension |
| 3096761 | 1986 | Clinical study | Eur J Respir Dis Suppl | Transdermal nitroglycerin lowered pulmonary artery pressure over 4 weeks |
| 42572609 | 2026 | Review | JHLT Open | Inhaled pulmonary vasodilators in the perioperative setting; notes nitroglycerin lacks pulmonary selectivity when given systemically |
| 39059783 | 2024 | Review | Curr Probl Cardiol | Advances in nebulised inhalation therapy for PAH |
| 26139748 | 2015 | Review | Ann Card Anaesth | Inhaled therapy for perioperative pulmonary hypertension |
New Zealand Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 2120313 | Rectogesic | Ointment 0.2% | Not stated (cancelled) |
| 716790 | Nitroderm TTS | Patch 25 mg, 5 mg per day | Not stated (cancelled) |
| 2017962 | Nitrolingual Pump Spray | Oral pump spray, 400 mcg per dose | Not stated (cancelled) |
| 750247 | Nitroderm TTS | Patch 50 mg, 10 mg per day | Not stated (cancelled) |
Safety Considerations
- Contraindications suggested by the knowledge graph (disease-level links, not label text): 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 ones include bupropion, morphine, canagliflozin, dapagliflozin, empagliflozin, dronabinol, nabilone, sapropterin and rosiglitazone. Minor-level ones include anticholinergics (atropine, hyoscyamine, scopolamine, glycopyrronium), acetylsalicylic acid and omeprazole.
- Practical concern: systemic vasodilation may cause hypotension. This is why inhaled delivery is being explored for pulmonary hypertension.
Please refer to the package insert for further safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The mechanism is plausible and acute haemodynamic benefit is shown in small studies, including one neonatal RCT. However, there are no completed Phase 2/3 trials, the registered trials are small or unverified, and all New Zealand licences are cancelled, so there is no marketed product or approved route for this use.
To proceed, the following is needed:
- Medsafe package insert warnings and contraindications (a blocking gap for safety screening)
- Detailed mechanism of action data from DrugBank
- Adequately powered controlled trials of nebulised or inhaled nitroglycerin with durable clinical outcomes
- A decision on formulation and route, since no inhaled product is currently licensed in New Zealand
- Clarification of the original approved indications of the cancelled licences
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.