Bumetanide
| Evidence Level: L4 | Predicted Indications: 1 |
Table of Contents
- Bumetanide
- Bumetanide: From Edema (Heart Failure, Hepatic and Renal Disease) to Acute Pulmonary Heart Disease
Bumetanide: From Edema (Heart Failure, Hepatic and Renal Disease) to Acute Pulmonary Heart Disease
One-Sentence Summary
Bumetanide is a potent loop diuretic used to treat edema associated with congestive heart failure and hepatic and renal disease. The TxGNN model predicts it may be effective for acute pulmonary heart disease (acute cor pulmonale), but the evidence is indirect: 3 registered trials (none testing this indication, one withdrawn) and 5 publications (all on general heart failure or diuretic pharmacology).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Edema associated with congestive heart failure, hepatic and renal disease (from a 1984 review; the US label text is not included in the source data) |
| Predicted New Indication | Acute pulmonary heart disease |
| TxGNN Prediction Score | 99.58% |
| Evidence Level | L4 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Bumetanide inhibits the NKCC2 cotransporter in the thick ascending limb of the loop of Henle. This produces rapid, marked diuresis and lowers intravascular volume and cardiac preload. In acute cor pulmonale, this could in theory relieve right-ventricular congestion and systemic venous overload. The mechanism fields in the source data are otherwise incomplete, so this rests on the known pharmacology of loop diuretics.
The link to the original use is plausible but indirect. Bumetanide is already used for acute pulmonary congestion and volume overload in heart failure. A small hemodynamic study (1987) showed that intravenous bumetanide lowered cardiac index and pulmonary artery occluded pressure in acute and chronic heart failure. However, all supporting data concern left-sided or general heart failure, not acute pulmonary heart disease such as right-ventricular strain from pulmonary embolism.
There is also a mechanistic caution. Acute cor pulmonale is often preload-dependent, so over-diuresis could lower cardiac output and worsen hemodynamics. The high TxGNN score is a computational prediction only, and no clinical evidence directly supports this indication.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT07375212 | Phase 4 | Withdrawn | 0 | Single 4 mg intranasal bumetanide dose, effect on pulmonary artery pressure and blood volume in heart failure patients with an implanted monitoring device (CardioMEMS/Cordella). Withdrawn, so no data. Population is heart failure, not acute pulmonary heart disease. |
| NCT05580510 | Phase 2/3 | Unknown | 160 | Empagliflozin and sacubitril/valsartan in adults with heart failure and congenital heart disease. Does not test bumetanide. |
| NCT06885164 | N/A | Recruiting | 200 | Seismocardiographic remote monitoring in heart failure. Non-interventional; does not evaluate bumetanide. |
All three trials were graded low relevance (C). None tests bumetanide in acute pulmonary heart disease.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 6391889 | 1984 | Review | Drugs | Bumetanide is a potent loop diuretic for edema in congestive heart failure, hepatic and renal disease, and acute pulmonary congestion. Diuresis begins within 30 minutes and lasts 3–6 hours. |
| 19142155 | 2009 | Review | Am J Ther | Reviews acute heart failure management and trial results. Diuretics are the mainstay for most patients. |
| 19843838 | 2009 | Review | Ann Pharmacother | Compares pharmacokinetics, safety, efficacy and cost of loop diuretics, asking whether furosemide should be first line. |
| 3304383 | 1987 | Clinical hemodynamic study | Br J Clin Pharmacol | In 24 patients with coronary artery disease and acute or chronic heart failure, IV bumetanide lowered cardiac index and pulmonary artery occluded pressure and raised systemic vascular resistance. |
| 39366035 | 2024 | Cohort/Epidemiology | Am J Emerg Med | Describes heart failure presentations to US emergency departments from 2016 to 2023. Background epidemiology only. |
US Market Information
Bumetanide is marketed in oral, injectable and intranasal forms. The source data list 20 authorizations in total; the main ones are below. Approved indication text was not provided for these entries.
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| NDA 219500 | Enbumyst | Spray (intranasal) | Corstasis USA LLC |
| ANDA 074700 | Bumetanide | Tablet | A-S Medication Solutions |
| ANDA 074700 | Bumetanide | Tablet | Sandoz Inc |
| ANDA 074700 | Bumetanide | Tablet | Bryant Ranch Prepack |
| ANDA 079196 | Bumetanide | Injection | Civica, Inc. |
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The TxGNN score is very high (99.58%), but no trial or publication directly evaluates bumetanide in acute pulmonary heart disease. Existing data concern left-sided or general heart failure. Diuresis may also be harmful in preload-dependent right-ventricular failure.
To proceed, the following is needed:
- Package insert warnings and contraindications, since safety screening cannot start without them
- Complete mechanism of action data from DrugBank
- Evidence in acute cor pulmonale or right-ventricular failure, such as hemodynamic studies or case series of loop diuretics in pulmonary embolism-related RV strain
- A risk assessment of over-diuresis and reduced cardiac output in preload-dependent patients
- A review of the intranasal formulation (Enbumyst) for acute-care suitability, since route compatibility has not been assessed
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before any application.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.