Eplerenone
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Eplerenone: From Hypertension to Pulmonary Hypertension
One-Sentence Summary
Eplerenone is a mineralocorticoid receptor (MR) antagonist, originally used to treat hypertension. The TxGNN model predicts it may be effective for pulmonary hypertension (with unclear multifactorial mechanism), with a very high score. However, no clinical trials and no publications specifically support this exact indication. Related pulmonary hypertension evidence is limited to preclinical studies listed under the closely related predicted indication "pulmonary hypertension owing to lung disease and/or hypoxia".
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Hypertension (hypertensive disorder). The Singapore licence records contain no approved indication text, so this comes from the knowledge-graph indication data |
| Predicted New Indication | Pulmonary hypertension with unclear multifactorial mechanism |
| TxGNN Prediction Score | 99.50% |
| Evidence Level | L5 (model prediction only) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 4 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known information, eplerenone is a selective mineralocorticoid receptor antagonist. It blocks the effects of aldosterone, which promotes sodium retention, vascular tone, inflammation and fibrosis. Its efficacy in hypertension is established, and mechanistically the same pathway may apply to pulmonary vascular disease.
A plausible link to pulmonary vascular remodelling exists through MR-mediated fibrosis, inflammation and vascular tone. Preclinical work in the related hypoxia-associated category supports this idea:
- Aldosterone synthesis is upregulated by hypoxia in pulmonary artery endothelial cells and promotes pulmonary vascular fibrosis (PMID 25001622).
- Aldosterone signalling drives abnormal pulmonary artery smooth muscle cell survival (PMID 27006450).
- Eplerenone attenuated pathological pulmonary vascular remodelling in a pulmonary arterial hypertension model, but not right ventricular remodelling (PMID 29499691).
- Treating established disease with MR antagonists improved interventricular dependence in a rat model (PMID 35043674).
This evidence is animal or cell-based. The high TxGNN score is a computational prediction only, and no human data for pulmonary hypertension were supplied.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
No publications were retrieved for the exact predicted indication. The table below lists the most relevant publications retrieved for the closely related category, pulmonary hypertension owing to lung disease and/or hypoxia. Most are preclinical or indirect.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 27230560 | 2016 | Clinical study (indirect) | Pol Arch Med Wewn | Eplerenone's effect on obstructive sleep apnoea severity and arterial stiffness in resistant hypertension |
| 41483355 | 2026 | Review | Curr Hypertens Rep | Aldosterone blockade for blood pressure control and oxygenation in sleep apnoea-related hypertension |
| 15199296 | 2004 | Review | Curr Opin Nephrol Hypertens | Glucocorticoid-mediated MR activation and hypertension |
| 35043674 | 2022 | Preclinical (rat) | Am J Physiol Lung Cell Mol Physiol | MR antagonists (eplerenone, spironolactone) in established PAH improved interventricular dependence |
| 29499691 | 2018 | Preclinical | BMC Pulm Med | Eplerenone attenuated pulmonary vascular remodelling rather than right ventricular remodelling in PAH |
| 25001622 | 2014 | Preclinical | Circulation | Hypoxia upregulates StAR, stimulating aldosterone synthesis and pulmonary vascular fibrosis |
| 27006450 | 2016 | Preclinical | FASEB J | Aldosterone-Raptor (mTORC1) signalling promotes abnormal pulmonary artery smooth muscle cell survival |
| 35568141 | 2022 | Preclinical (rat) | Cardiovasc Pathol | Eplerenone improved atrial remodelling in a chronic intermittent hypoxia model |
| 35346763 | 2022 | Preclinical (rat) | Exp Gerontol | Chronic intermittent hypoxia induces renal fibrosis through MR activation |
Other retrieved papers (liver cirrhosis, choroidal blood flow, renal protection) are off-target and are not listed.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN13048P | INSPRA TABLETS 25mg (Viatris) | Tablet, coated | Not stated in the records |
| SIN13049P | INSPRA TABLETS 50mg (Viatris) | Tablet, coated | Not stated in the records |
| SIN16941P | EPLERENONE MEVON FILM-COATED TABLETS 25 MG (Pharmathen) | Tablet, film coated | Not stated in the records |
| SIN16940P | EPLERENONE MEVON FILM-COATED TABLETS 50 MG (Pharmathen) | Tablet, film coated | Not stated in the records |
All four licences are valid single-ingredient oral products, and none has been cancelled.
Safety Considerations
- Disease-related cautions (knowledge-graph contraindication data, not label text): liver disease, gallbladder disease, diabetic nephropathy, and impaired renal function disease.
- Drug Interactions: 100 interactions were identified. Examples of Major interactions include:
- Aprepitant
- Clarithromycin
- Clotrimazole
- Potassium chloride, potassium citrate and potassium bicarbonate (raised hyperkalaemia risk)
Moderate interactions include corticosteroids (hydrocortisone, dexamethasone, prednisone and others), SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin), acetylsalicylic acid, bupropion, miconazole, and the cannabinoids dronabinol and nabilone.
Please refer to the package insert for warnings and formal contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is very high and the mechanism is biologically plausible. However, there are no clinical trials or publications for this exact indication, so the evidence level is L5. Related evidence for hypoxia-associated pulmonary hypertension is preclinical (L4) and mixed, with a possible vascular benefit but doubtful right ventricular benefit.
To proceed, the following is needed:
- Package insert warnings and contraindications from the HSA website (a blocking gap for safety screening)
- Detailed mechanism of action data from DrugBank
- Human clinical data for eplerenone in pulmonary hypertension, such as pilot trials or case series
- A safety plan covering hyperkalaemia and renal function monitoring, given the major potassium and CYP3A4-inhibitor interactions
- Clarification of the approved indication text for the Singapore licences
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.