Nitroglycerin
| Evidence Level: L3 | Predicted Indications: 5 |
Table of Contents
Nitroglycerin: From Angina Pectoris to Pulmonary Hypertension
One-Sentence Summary
Nitroglycerin is a nitric oxide (NO) donor and vasodilator, long used for angina (the US license data compiled for this report do not list an approved indication text). The TxGNN model predicts it may be effective for pulmonary hypertension, with 3 clinical trials (1 completed, 1 of unknown status, 1 not yet recruiting) and 20 publications currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available in the license data (nitroglycerin is a long-established vasodilator used for angina) |
| Predicted New Indication | Pulmonary hypertension |
| TxGNN Prediction Score | 99.61% |
| Evidence Level | L3 |
| US Market Status | Cancelled only (no currently valid licenses) |
| Number of NDAs | 9 (all cancelled) |
| 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, nitroglycerin is a nitric oxide donor. NO activates soluble guanylate cyclase, raises cGMP in vascular smooth muscle, and causes vasodilation.
Pulmonary hypertension is driven in large part by pulmonary vasoconstriction and elevated pulmonary vascular resistance. Vasodilator pathways such as inhaled NO, PDE5 inhibitors and sGC stimulators are already used in this condition. Delivered by nebulization, nitroglycerin may act as a relatively selective pulmonary vasodilator with less systemic hypotension than intravenous use. This is mechanistically coherent with the high TxGNN score.
An important caveat: the evidence is mostly hemodynamic, perioperative or small-scale. Systemic nitroglycerin is non-selective and can cause hypotension, and the supporting studies are not definitive trials of long-term efficacy.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT07214129 | N/A | Completed | 20 | Nebulized nitroglycerin as a vasoreactive agent in pulmonary arterial hypertension; directly relevant but small, no results summarized |
| NCT04594629 | Phase 1 | Unknown | 120 | Nebulized PGI2 (epoprostenol) vs nebulized nitroglycerin for pulmonary hypertension after valve replacement surgery; randomized, results unverified |
| NCT07603037 | N/A | Not yet recruiting | 12 | Nicardipine vs nitroglycerin effects on ventilation-perfusion ratio in acute respiratory failure; only tangentially related |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 40888971 | 2025 | RCT | Eur J Pediatr | Nebulized nitroglycerin as an adjuvant in persistent pulmonary hypertension of the newborn (80 neonates); 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 pulmonary arterial hypertension in children with congenital heart disease |
| 16707530 | 2006 | Clinical study | Br J Anaesth | Inhaled nitroglycerin acutely affects pulmonary and systemic haemodynamics in children with PAH and congenital heart disease |
| 6407380 | 1983 | Hemodynamic study | Ann Intern Med | In 9 patients with chronic pulmonary hypertension, nitroglycerin raised cardiac index about 40% and lowered pulmonary vascular resistance about 40% |
| 6423015 | 1984 | Hemodynamic study | Bull Eur Physiopathol Respir | In COPD-related pulmonary hypertension, nitroglycerin lowered pulmonary arterial pressure and, unlike isosorbide dinitrate, pulmonary vascular resistance |
| 3096761 | 1986 | Clinical study | Eur J Respir Dis Suppl | Transdermal nitroglycerin lowered pulmonary artery pressure, with the effect sustained over 4 weeks |
| 8908227 | 1996 | Hemodynamic study | Acta Anaesthesiol Scand | Pulmonary vascular effects of nitroglycerin vs isosorbide dinitrate in end-stage cardiomyopathy |
| 42572609 | 2026 | Review | JHLT Open | Inhaled pulmonary vasodilators in the perioperative setting; notes that nitroglycerin lacks pulmonary selectivity |
| 26139748 | 2015 | Review | Ann Card Anaesth | Inhaled therapy for perioperative pulmonary hypertension as an alternative to inhaled NO |
US Market Information
All nine US authorizations are cancelled; none is currently valid. Indication text is not available for any of them.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA020145 | Nitroglycerin Transdermal Infusion System | Patch | Not available |
| NDA021134 | Nitroglycerin | Tablet | Not available |
| ANDA217879 | Nitroglycerin | Tablet | Not available |
| ANDA091496 | Nitroglycerin lingual | Spray | Not available |
| ANDA072034 | Nitroglycerin | Injection, solution | Not available |
Safety Considerations
- Contraindication signals (from a knowledge graph, 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 in total. Moderate-level examples include morphine, bupropion, the SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin), dronabinol, nabilone, sapropterin and rosiglitazone. Minor-level examples include aspirin, omeprazole, and anticholinergics (atropine, hyoscyamine, scopolamine, glycopyrronium).
For label-based warnings and contraindications, please refer to the package insert.
Conclusion and Next Steps
Decision: Hold
Rationale: The biological rationale is coherent and there are small randomized and hemodynamic studies, including a 2025 RCT in neonatal PPHN. However, there is no completed Phase 2/3 RCT, the main comparator trial is of unknown status, and all US licenses are cancelled. Label-based safety data are also missing. This is best treated as a research question rather than a candidate for advancement now.
To proceed, the following is needed:
- FDA package insert warnings and contraindications (a blocking gap for safety screening)
- Mechanism of action data from DrugBank
- Results from the completed nebulized nitroglycerin PAH study (NCT07214129) and verification of the status of NCT04594629
- Adequately powered controlled trials of the nebulized route, with a hypotension and gas-exchange monitoring plan
- A formulation and route plan, since no inhaled product is currently authorized in the US
Other predicted indications (brief): Prinzmetal angina (score 99.39%, L4) is supported by general reviews and long-standing nitrate use, but this is probably existing practice rather than true repurposing. Kyphoscoliotic heart disease, primary hereditary glaucoma and congenital hypotrichosis milia have no clinical or literature evidence and little plausible mechanism, so Hold is recommended.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.