Nitroglycerin
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
Nitroglycerin: From Angina and Other Cardiovascular Uses to Pulmonary Hypertension
One-Sentence Summary
Nitroglycerin is a nitric oxide (NO) donor and vasodilator. It is marketed in Singapore in sublingual, spray, injectable, infusion and ointment forms, but the data compiled for this report do not include approved indication text. The TxGNN model predicts it may be effective for pulmonary hypertension, with 3 registered clinical trials (2 directly relevant) and 20 publications currently supporting this direction. The evidence is mainly small studies, hemodynamic studies and reviews, and no completed Phase 2/3 randomized trial was identified.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available (the Singapore licence records contain no approved indication text) |
| Predicted New Indication | Pulmonary hypertension |
| TxGNN Prediction Score | 99.61% |
| Evidence Level | L3 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 5 |
| Recommended Decision | Proceed with Guardrails |
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. It activates soluble guanylate cyclase, which raises cGMP and relaxes vascular smooth muscle. This produces vasodilation and lowers cardiac preload.
In pulmonary hypertension the same pathway can lower pulmonary vascular resistance and pulmonary artery pressure. The main concern with systemic delivery is non-selective vasodilation, which can cause hypotension. Inhaled or nebulized delivery may give relative pulmonary selectivity and limit systemic effects. Hemodynamic studies from the 1980s (for example, nine patients with chronic pulmonary hypertension) reported falls in pulmonary vascular resistance and pulmonary artery pressure. More recent work on nebulized nitroglycerin in children and neonates is consistent with this.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT07214129 | Not labelled | Completed | 20 | Nebulized nitroglycerin as a vasoreactivity agent in pulmonary arterial hypertension; small study |
| NCT04594629 | Phase 1 | Unknown | 120 | Randomized comparison of nebulized epoprostenol (PGI2) vs nebulized nitroglycerin for pulmonary hypertension after valve replacement surgery |
| NCT07603037 | Not labelled | Not yet recruiting | 12 | Nicardipine vs nitroglycerin on ventilation-perfusion ratio in acute respiratory failure with hypertension; only tangentially related |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 40888971 | 2025 | RCT | Eur J Pediatr | 80 neonates with persistent pulmonary hypertension; nebulized nitroglycerin as an adjuvant, assessed by echocardiographic and clinical parameters |
| 29880427 | 2018 | RCT | J Cardiothorac Vasc Anesth | Dobutamine plus nitroglycerin vs milrinone for perioperative pulmonary hypertension in mitral valve surgery |
| 34082850 | 2021 | Review | Cardiol Young | Nitroglycerin inhalation 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 hemodynamics in children with congenital heart disease |
| 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 nebulized inhalation therapy for pulmonary arterial hypertension |
| 6407380 | 1983 | Hemodynamic study | Ann Intern Med | In 9 patients, nitroglycerin raised cardiac index about 40% and lowered pulmonary vascular resistance about 40% |
| 6423015 | 1984 | Hemodynamic study | Bull Eur Physiopathol Respir | In 27 COPD patients, nitroglycerin lowered pulmonary vascular resistance, while isosorbide dinitrate did not |
| 3096761 | 1986 | Clinical study | Eur J Respir Dis Suppl | Transdermal nitroglycerin lowered pulmonary artery pressure, sustained over 4 weeks |
| 26139748 | 2015 | Review | Ann Card Anaesth | Inhaled therapies for perioperative pulmonary hypertension, including alternatives to nitric oxide |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN12240P | RECTOGESIC OINTMENT 0.2% w/w | Ointment | Not stated in available records |
| SIN15702P | MYONIT INSTA Nitroglycerin Sublingual Tablets USP 0.5 mg | Tablet | Not stated in available records |
| SIN15510P | GLYDEX IV Solution for Injection 1 mg/ml | Injection | Not stated in available records |
| SIN09161P | GLYTRIN SPRAY | Spray | Not stated in available records |
| SIN15105P | GLYCERYL TRINITRATE-HAMELN INJECTION 1 mg/ml | Infusion, solution | Not stated in available records |
All five registrations are valid single-ingredient products. No inhaled or nebulized product is registered, so the route studied for pulmonary hypertension would be off-label in Singapore.
Safety Considerations
- Contraindications (from knowledge-graph drug-disease links, not label text): hypotensive disorder, hypertrophic cardiomyopathy, methemoglobinemia, sulfhemoglobinemia, anemia, macrocytic anemia, intracerebral hemorrhage, constrictive pericarditis, restrictive cardiomyopathy, cardiac tamponade.
- Drug Interactions: 100 interactions were identified, and the first 20 retrieved are listed below.
- Moderate: bupropion, morphine, canagliflozin, dapagliflozin, empagliflozin, dronabinol, nabilone, sapropterin, rosiglitazone.
- Minor: hyoscyamine, atropine, scopolamine, glycopyrronium, dicyclomine, trospium, mepenzolate, methscopolamine, propantheline, acetylsalicylic acid, omeprazole.
- Considerations for pulmonary hypertension use: systemic hypotension is the main risk with non-selective vasodilation, which is why inhaled delivery is being studied. Package insert warnings and contraindications were not available in the compiled data, so please refer to the package insert.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale:
- The NO-cGMP mechanism is plausible for pulmonary vasodilation. Hemodynamic studies, a recent neonatal RCT and a small completed trial of nebulized nitroglycerin point in the same direction. However, no completed Phase 2/3 RCT exists, the registered trials are small, and the best-supported route (inhaled) is not registered in Singapore.
To proceed, the following is needed:
- Package insert warnings and contraindications from the HSA, which are currently missing
- Mechanism of action data from DrugBank
- Results of NCT07214129 and NCT04594629, and ideally an adequately powered randomized trial of nebulized nitroglycerin
- A route and formulation plan for inhaled use, since no inhaled product is registered
- A hemodynamic monitoring plan to manage hypotension risk
Other Predicted Indications (for reference)
| Predicted Indication | Evidence Level | Decision | Comment | |------|------|------|------| | Prinzmetal angina | L4 | Research Question | Nitrates are part of standard management of coronary vasospasm. The literature is mostly older reviews, with no registered trials | | Open-angle glaucoma | L4 | Hold | Indirect evidence only (old nitrate report, hypothesis paper, nipradilol study). Systemic hypotension may reduce optic nerve perfusion | | Transient ischemic attack | L4 | Hold | Only cerebral vasospasm reports, with no direct evidence. Possible intracranial pressure concerns | | Headache disorder | L4 | Hold | Nitroglycerin triggers migraine and is used as an induction model, which points against therapeutic use | | Kyphoscoliotic heart disease, primary hereditary glaucoma, congenital hypotrichosis milia, alopecia, hypotrichosis simplex of the scalp | L5 | Hold | Model prediction only, with no supporting trials or literature |
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.