Nitroglycerin
| Evidence Level: L3 | Predicted Indications: 5 |
Table of Contents
Nitroglycerin: From an Unspecified Registered Indication to Pulmonary Hypertension
One-Sentence Summary
Nitroglycerin is a nitric oxide (NO)-donating vasodilator, registered in South Africa as the Nitrolingual inhaler. The SAHPRA registration data compiled for this report do not state an approved indication. The TxGNN model predicts it may be effective for pulmonary hypertension, with 3 registered clinical trials and 20 publications currently supporting this direction. Most of these are reviews, small haemodynamic studies or small trials of nebulized nitroglycerin.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the SAHPRA registration data compiled for this report |
| Predicted New Indication | Pulmonary hypertension |
| TxGNN Prediction Score | 99.61% |
| Evidence Level | L3 |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 1 |
| Recommended Decision | Hold (treat as a research question) |
Why is This Prediction Reasonable?
Detailed mechanism of action data are not available in the data compiled for this report. Nitroglycerin is a well-known organic nitrate. Its metabolism releases nitric oxide, which activates soluble guanylate cyclase, raises cGMP and relaxes vascular smooth muscle. This is the same pathway that underlies its long-established use in angina.
In pulmonary hypertension, persistent pulmonary vasoconstriction is a core problem. A vasodilator acting through the NO–cGMP pathway is therefore biologically plausible. It is consistent with inhaled nitric oxide and PDE5 inhibitors, which already target this pathway. Delivering nitroglycerin by inhalation or nebulization could produce relatively selective pulmonary vasodilation with less systemic hypotension. This is a hypothesis, not an established benefit. Older literature also notes that non-selective vasodilators can cause systemic hypotension or worsen ventilation-perfusion matching.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT07214129 | Not applicable | Completed | 20 | Nebulized nitroglycerin as a vasoreactivity agent in pulmonary arterial hypertension. Small study, no results available. |
| NCT04594629 | Phase 1 | Unknown | 120 | Nebulized prostacyclin (epoprostenol) vs nebulized nitroglycerin for pulmonary hypertension after valve replacement surgery. Randomized, no results available. |
| NCT07603037 | Not applicable | Not yet recruiting | 12 | Nicardipine and nitroglycerin effects on ventilation-perfusion distribution in acute respiratory failure. Only indirectly related. |
No SANCTR or PACTR identifiers were found in the data compiled for this report.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 40888971 | 2025 | RCT (n=80) | Eur J Pediatr | Nebulized nitroglycerin as an adjuvant in persistent pulmonary hypertension of the newborn, assessing echocardiographic and clinical parameters |
| 29880427 | 2018 | RCT | J Cardiothorac Vasc Anesth | Dobutamine and nitroglycerin vs milrinone for perioperative pulmonary hypertension in mitral valve surgery |
| 16707530 | 2006 | Clinical study | Br J Anaesth | Inhaled nitroglycerin in children with congenital heart disease and pulmonary arterial hypertension, assessing acute haemodynamic effects |
| 34082850 | 2021 | Review | Cardiol Young | Nitroglycerin inhalation for acute pulmonary arterial hypertension in children with congenital heart disease |
| 6407380 | 1983 | Haemodynamic study | Ann Intern Med | In nine patients with chronic pulmonary hypertension, nitroglycerin increased cardiac index by 40% and decreased pulmonary vascular resistance by 40% |
| 6423015 | 1984 | Haemodynamic study | Bull Eur Physiopathol Respir | In 27 COPD patients, nitroglycerin reduced pulmonary vascular resistance; isosorbide dinitrate did not |
| 8908227 | 1996 | Clinical study | Acta Anaesthesiol Scand | Pulmonary vascular effects of nitroglycerin and isosorbide dinitrate in end-stage cardiomyopathy |
| 6430080 | 1984 | Review | Am J Med | Nitroglycerin in pulmonary hypertensive disorders; non-selective vasodilators risk systemic hypotension |
| 42572609 | 2026 | Review | JHLT Open | Inhaled pulmonary vasodilators in the perioperative setting |
| 39059783 | 2024 | Review | Curr Probl Cardiol | Advances in nebulized inhalation therapy for pulmonary arterial hypertension |
South Africa Market Information
| Registration Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| P/7.1.4/281 | Nitrolingual | Inhaler | Not stated in the data compiled for this report |
The Essential Medicines List (EML) status of this product could not be determined from the data compiled for this report.
Safety Considerations
Contraindication signals from the TxGNN knowledge graph (derived from drug–disease relationship edges, not from label text): hypotensive disorder, hypertrophic cardiomyopathy, methemoglobinemia, sulfhemoglobinemia, anaemia (including macrocytic anaemia), intracerebral haemorrhage, constrictive pericarditis, restrictive cardiomyopathy and cardiac tamponade.
Drug interactions: 228 potential interactions were identified. Those listed include:
- Moderate: bupropion, morphine, canagliflozin, dapagliflozin, empagliflozin, dronabinol, nabilone, sapropterin, rosiglitazone
- Minor: acetylsalicylic acid, omeprazole, and anticholinergics such as atropine, hyoscyamine, scopolamine, glycopyrronium, dicyclomine, trospium, mepenzolate, methscopolamine and propantheline
Please refer to the SAHPRA-approved Professional Information (PI) for warnings and contraindications. Report adverse drug reactions to SAHPRA.
Other Predicted Indications (Lower Priority)
| Predicted Indication | TxGNN Score | Evidence Level | Comment |
|---|---|---|---|
| Prinzmetal angina | 99.39% | L4 | Coronary vasospasm responds to nitrates, so this is close to existing use rather than true repurposing. The literature is mostly reviews and older studies; no nitroglycerin-specific controlled trial and no registered trials. |
| Kyphoscoliotic heart disease | 99.42% | L5 | Prediction only. Vasodilators may worsen ventilation-perfusion matching in restrictive lung disease. |
| Primary hereditary glaucoma | 99.16% | L5 | Prediction only. The NO–cGMP pathway is relevant to outflow, but there is no clinical support. |
| Congenital hypotrichosis milia | 99.02% | L5 | Prediction only. No plausible mechanistic rationale. |
Conclusion and Next Steps
Decision: Hold (treat as a research question)
Rationale: The mechanism is plausible and there is a body of small studies and reviews on nebulized or inhaled nitroglycerin. However, the clinical trials are small, early-phase, non-phased or without results. There is no completed Phase 2/3 RCT, and the registered indication and safety labelling for the local product are missing from the data compiled for this report. Safety review cannot be completed without the SAHPRA package insert.
To proceed, the following is needed:
- The SAHPRA package insert, to confirm the approved indication, warnings and contraindications for Nitrolingual
- Mechanism of action data from DrugBank
- Confirmation that an inhaled or nebulized formulation suitable for pulmonary hypertension is available and registered locally; the registered inhaler’s route and use must be reconciled with the trial routes
- Results from NCT07214129 and NCT04594629, and ideally a well-powered Phase 2 RCT in pulmonary arterial hypertension
- A haemodynamic safety plan covering systemic hypotension, oxygenation and ventilation-perfusion matching
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.