Nitroglycerin
| Evidence Level: L3 | Predicted Indications: 4 |
Table of Contents
- Nitroglycerin
- Pharmacist Assessment Report
- Nitroglycerin: From Angina Pectoris to Pulmonary Hypertension
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Canada Market Information
- Safety Considerations
- Other Predicted Indications (Brief)
- Conclusion and Next Steps
- Disclaimer
Nitroglycerin: From Angina Pectoris to Pulmonary Hypertension
One-Sentence Summary
Nitroglycerin is a nitric oxide (NO) donor and vasodilator, long marketed in Canada as patches, sprays, sublingual products and an intravenous solution. The TxGNN model predicts it may be effective for Pulmonary Hypertension, with 3 clinical trials (none of them a completed Phase 2/3 RCT) and 20 publications currently supporting this direction, mostly small hemodynamic studies, reviews and perioperative reports.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the Canadian licence data compiled for this report (nitroglycerin is a long-established vasodilator used for angina) |
| Predicted New Indication | Pulmonary hypertension |
| TxGNN Prediction Score | 0.9961 |
| Evidence Level | L3 |
| Canada Market Status | Marketed (marketed DINs: 18 of 18) |
| Number of DINs | 18 (marketed: 18) |
| Recommended Decision | Proceed with Guardrails (as a research question) |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data are not available in the data compiled for this report. Based on known pharmacology, nitroglycerin releases nitric oxide, which activates soluble guanylate cyclase and raises cGMP in vascular smooth muscle, producing vasodilation.
This NO–cGMP pathway is the same one targeted by established pulmonary vasodilators. Delivering nitroglycerin by inhalation or nebulization may lower pulmonary vascular resistance with less systemic effect. The most relevant settings are acute vasoreactivity testing and perioperative care. Evidence for long-term, disease-modifying benefit is lacking.
The original indication could not be extracted from the licence data, so the link between the original and new indication rests on the shared vasodilator mechanism.
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; small, non-phased study |
| NCT04594629 | Phase 1 | Unknown | 120 | Nebulized prostacyclin (PGI2) vs nebulized nitroglycerin for pulmonary hypertension after valve replacement surgery; results may be unreported |
| NCT07603037 | N/A | Not yet recruiting | 12 | Nicardipine vs nitroglycerin effects on ventilation-perfusion ratio in acute respiratory failure; only indirectly relevant |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 29880427 | 2018 | RCT | J Cardiothorac Vasc Anesth | Dobutamine plus nitroglycerin compared with milrinone for perioperative pulmonary hypertension in mitral valve surgery |
| 16707530 | 2006 | Clinical study | Br J Anaesth | Inhaled nitroglycerin acutely reduced pulmonary arterial hypertension in children with congenital heart disease |
| 34082850 | 2021 | Review/cohort | Cardiol Young | Inhaled nitroglycerin as an alternative to nitric oxide for acute pulmonary hypertension in children with congenital heart disease |
| 6407380 | 1983 | Hemodynamic study | Ann Intern Med | In 9 patients with chronic pulmonary hypertension, nitroglycerin lowered pulmonary vascular resistance by about 40% and raised cardiac index by 40% |
| 6423015 | 1984 | Hemodynamic study | Bull Eur Physiopathol Respir | In COPD-related pulmonary hypertension, nitroglycerin lowered pulmonary artery pressure and pulmonary vascular resistance |
| 3096761 | 1986 | Clinical study | Eur J Respir Dis Suppl | Transdermal nitroglycerin lowered pulmonary artery pressure, sustained over 4 weeks |
| 8908227 | 1996 | Clinical study | Acta Anaesthesiol Scand | Pulmonary vascular effects of nitroglycerin vs isosorbide dinitrate in end-stage cardiomyopathy |
| 6430080 | 1984 | Clinical review | Am J Med | Nitroglycerin in pulmonary hypertensive disorders; nonselective vasodilators risk systemic hypotension |
| 42572609 | 2026 | Review | JHLT Open | Inhaled pulmonary vasodilators in the perioperative setting; nitroglycerin lacks pulmonary selectivity when given systemically |
| 39059783 | 2024 | Review | Curr Probl Cardiol | Advances in nebulized inhalation therapy for pulmonary arterial hypertension |
Canada Market Information
Eighteen valid licences are held in Canada. Dosage form and approved-indication text were not available in the licence data. The main products are listed below.
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 00037621 | NITROSTAT | Not specified | Not specified |
| 02231441 | NITROLINGUAL PUMPSPRAY | Spray (by product name) | Not specified |
| 02238998 | RHO-NITRO PUMPSPRAY | Spray (by product name) | Not specified |
| 02407469 | MYLAN-NITRO PATCH 0.6 | Patch (by product name) | Not specified |
| 02145308 | NITROGLYCERIN IN 5% DEXTROSE INJ.-200MCG/ML | Injection (by product name) | Not specified |
The remaining licences cover other patch strengths (Nitro-Dur, Trinipatch, Mylan-Nitro), a second Nitrostat DIN, Nitroject, and a 400 mcg/mL intravenous solution.
Safety Considerations
- Contraindication-related conditions (from the 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 found in total. Moderate-level interactions include bupropion, morphine, canagliflozin, dapagliflozin, empagliflozin, dronabinol, nabilone, sapropterin and rosiglitazone. Minor-level interactions include several anticholinergics (atropine, hyoscyamine, glycopyrronium, scopolamine), acetylsalicylic acid and omeprazole.
- Context-specific concern: systemic nitroglycerin is not pulmonary-selective and can cause systemic hypotension, so route and monitoring matter for pulmonary hypertension use.
Package insert warnings and contraindications were not available. Please refer to the package insert for full safety information.
Other Predicted Indications (Brief)
| Predicted Indication | TxGNN Score | Evidence Level | Note |
|---|---|---|---|
| Kyphoscoliotic heart disease | 0.9942 | L5 | No trials or literature; vasodilators may worsen ventilation-perfusion mismatch |
| Primary hereditary glaucoma | 0.9916 | L5 | No trials or literature; no established role |
| Congenital hypotrichosis milia | 0.9902 | L5 | No plausible mechanistic link identified |
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: The NO–cGMP mechanism is biologically plausible, and there are small hemodynamic studies, one randomized perioperative comparison and a few small trials in pulmonary hypertension. However, no completed Phase 2/3 RCT exists, and the benefit appears limited to acute and perioperative use, so this should be handled as a research question.
To proceed, the following is needed:
- Health Canada package insert warnings and contraindications (a blocking gap for safety screening)
- Mechanism of action data from DrugBank
- Approved indication and dosage form details for the Canadian licences
- Results from NCT04594629, and a larger controlled study of inhaled or nebulized nitroglycerin
- A hypotension and hypoxemia monitoring plan for the inhaled route
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.