Nebivolol
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Nebivolol: From Hypertension to Malignant Hypertensive Renal Disease
One-Sentence Summary
Nebivolol is a beta-blocker originally used to treat hypertension. The TxGNN model predicts it may be effective for malignant hypertensive renal disease, but there are currently no clinical trials and no publications supporting this specific prediction. The score appears to reflect closeness to the original hypertension indication rather than new evidence.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Hypertension (hypertensive disorder); the Singapore licence records contain no indication text |
| Predicted New Indication | Malignant hypertensive renal disease |
| TxGNN Prediction Score | 99.42% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 4 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available. From general pharmacology, nebivolol is a highly beta-1 selective blocker that also promotes vasodilation through endothelial nitric oxide release. This explains its established use in hypertension.
Malignant hypertensive renal disease is a severe form of the same condition, which is why the model scores it so highly. However, malignant hypertension is a hypertensive emergency, normally managed with intravenous agents, and oral nebivolol is not a standard option. The high score most likely reflects proximity to the original indication rather than a genuine new repurposing signal.
Other predictions reviewed for this drug:
- Malignant renovascular hypertension (99.42%): a secondary hypertension subtype. Beta-blockade lowers renin release, which is mechanistically relevant, but there is no direct evidence (L5, Hold).
- Pulmonary hypertension, unclear multifactorial mechanism (99.39%): nitric oxide-mediated vasodilation could theoretically help. Beta-blockers are used cautiously in pulmonary arterial hypertension because of right ventricular concerns (L5, Hold).
- Pulmonary hypertension owing to lung disease and/or hypoxia (99.39%): the literature is mostly preclinical or off-topic (L4, Hold).
- Chronic pulmonary heart disease (91.85%): the most developed signal beyond the top prediction. It has one Phase 4 trial and literature supporting safety in heart failure with COPD, but the evidence is indirect (L4, Research Question).
- Prinzmetal angina (87.48%): one related recruiting trial, with a safety caution on vasospasm (L4, Hold).
- Braddock syndrome, ocular tuberculosis, congenital temporomandibular joint ankylosis and polydipsia: no plausible mechanistic link and no evidence (L5, Hold).
Clinical Trial Evidence
Currently no related clinical trials registered for malignant hypertensive renal disease.
For reference, trials found for other predicted indications:
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00517725 | Phase 4 | Completed | 60 | Nebivolol vs bisoprolol vs carvedilol in heart failure, comparing effects on exercise capacity, hypoxia, chemoreceptor response and lung function (relevant to chronic pulmonary heart disease, indirectly) |
| NCT06424834 | Phase 2/3 | Recruiting | 150 | Targeted medical therapy vs placebo in angina with non-obstructive coronary arteries; not specific to Prinzmetal angina, and nebivolol's role is unconfirmed |
Literature Evidence
Currently no related literature available for malignant hypertensive renal disease.
For reference, the most relevant publications found for related predicted indications (chronic pulmonary heart disease and pulmonary hypertension due to lung disease or hypoxia):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 29159953 | 2018 | Cohort | Eur J Heart Fail | Danish nationwide cohort comparing carvedilol with metoprolol/bisoprolol/nebivolol in heart failure with COPD |
| 31391573 | 2019 | Cohort | Sci Rep | Italian register study of beta-blocker choice in heart failure with COPD |
| 21516766 | 2011 | Clinical study | Klin Med | In 50 patients with coronary heart disease and COPD, nebivolol lowered blood pressure and heart rate and did not adversely affect bronchial patency |
| 15031571 | 2004 | Clinical study | Respiration | Two-week comparison of nebivolol and nifedipine in hypertensive patients with COPD |
| 23506636 | 2013 | Clinical trial | Int J Cardiol | CARNEBI: carvedilol vs nebivolol vs bisoprolol in moderate heart failure |
| 21883997 | 2012 | RCT | Cardiovasc Ther | Nebivolol vs carvedilol on exercise performance at high altitude in healthy subjects |
| 19815121 | 2009 | Review | J Am Coll Cardiol | Overview of nebivolol's high beta-1 affinity and endothelial nitric oxide effects |
| 30426333 | 2018 | Review | Drugs | Critical review of nebivolol and its fixed-dose combinations in hypertension, including use in patients with COPD |
| 32128711 | 2020 | Preclinical (animal) | Pharmacol Rep | Nebivolol showed renal protection in rat models of acute renal injury |
| 36947849 | 2023 | Preclinical (animal) | Can J Physiol Pharmacol | Nebivolol protected against methotrexate-induced nephrotoxicity in rats |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN11728P | NEBILET TABLET 5 mg | Tablet | Not stated in the registration record |
| SIN16446P | NEVODIO TABLET 5MG | Tablet | Not stated in the registration record |
| SIN16481P | NEBIVOLOL STELLA TABLET 5MG | Tablet | Not stated in the registration record |
| SIN15958P | NEVOPRES TABLET 5MG | Tablet | Not stated in the registration record |
All four are valid single-ingredient oral tablet licences.
Safety Considerations
Package insert warnings and contraindications were not available. Please refer to the package insert for safety information.
- Contraindication-related conditions (from the knowledge graph, not label text): liver failure, liver disease, gallbladder disease, diabetes mellitus, diabetic ketoacidosis, peripheral vascular disease, intermittent claudication, peripheral arterial disease, hypoglycaemia, atrioventricular block, bronchial disease, sick sinus syndrome, familial sick sinus syndrome.
- Drug Interactions: 100 interactions were recorded. Those listed are mostly moderate: epinephrine, hydrocortisone, dexamethasone, betamethasone, budesonide, triamcinolone, morphine, bupropion, atropine, hyoscyamine, glycopyrronium, dicyclomine, lorcaserin, canagliflozin, dapagliflozin, chlorpropamide, calcium phosphate and calcium acetate. Minor ones include acetylsalicylic acid and magnesium oxide.
- Indication-specific cautions: beta-blockers need caution in pulmonary arterial hypertension (right ventricular function) and in vasospastic angina (possible worsening of vasospasm).
Conclusion and Next Steps
Decision: Hold
Rationale: The predicted indication has no clinical trials or publications (L5, model prediction only). The high score likely reflects ontology proximity to hypertension, and malignant hypertension is an emergency typically treated with intravenous agents. Of the other predictions, chronic pulmonary heart disease is the only one with an indirect evidence base, and it is better framed as a research question than a repurposing recommendation.
To proceed, the following is needed:
- Package insert warnings and contraindications from the HSA website (a blocking data gap for safety screening)
- Detailed mechanism of action data from DrugBank
- Clinical or observational evidence of oral nebivolol in malignant hypertension with renal involvement, or a clear rationale for its role relative to standard intravenous therapy
- For chronic pulmonary heart disease, studies directly enrolling cor pulmonale patients, with attention to right ventricular safety
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.