Eplerenone

Evidence Level: L5

Predicted Indications: 4

Eplerenone

Pharmacist Assessment Report

Eplerenone: From Hypertension to Pulmonary Hypertension Owing to Lung Disease and/or Hypoxia

One-Sentence Summary

Eplerenone is a selective mineralocorticoid receptor (MR) antagonist, originally used to treat hypertension. The TxGNN model predicts it may be useful for pulmonary hypertension owing to lung disease and/or hypoxia, but there are currently no registered clinical trials and only preclinical and indirect literature supporting this direction.

Quick Overview

Item	Content
Original Indication	Hypertension (hypertensive disorder); the ARTG entry in the data compiled for this report has no indication text
Predicted New Indication	Pulmonary hypertension owing to lung disease and/or hypoxia
TxGNN Prediction Score	0.9950
Evidence Level	L5
Australia Market Status	Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data
Number of PBS Items	1 (valid: 1)
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 MR antagonist. Its efficacy in hypertension is established, and mechanistically it may be applicable to hypoxia-related pulmonary vascular disease.

Aldosterone and MR signalling are involved in vascular inflammation, fibrosis and remodelling. In rodent models of chronic intermittent hypoxia, eplerenone attenuated renal fibrosis and atrial remodelling. Preclinical pulmonary arterial hypertension work also suggests that aldosterone drives pulmonary vascular fibrosis and smooth muscle cell abnormalities under hypoxia, and that MR blockade improves pulmonary vascular remodelling. This provides a plausible link between the original indication (hypertension, a disease of vascular tone and remodelling) and the predicted indication.

However, this evidence is almost entirely animal or cell-based, and no direct human evidence in pulmonary hypertension due to lung disease or hypoxia was found. One animal study also found that MR antagonism with losartan was ineffective in experimental right ventricular failure, so the evidence is mixed.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

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	Reviews aldosterone blockade for blood pressure and oxygenation in obstructive sleep apnoea
15199296	2004	Review	Curr Opin Nephrol Hypertens	Glucocorticoid-mediated MR activation and hypertension
35043674	2022	Preclinical (animal)	Am J Physiol Lung Cell Mol Physiol	MR antagonists (eplerenone, spironolactone) in established PAH in the SU5416-hypoxia rat model; improved interventricular dependence
29499691	2018	Preclinical (animal)	BMC Pulm Med	Eplerenone attenuated pulmonary vascular remodelling rather than right ventricular remodelling in PAH
25001622	2014	Preclinical (mechanistic)	Circulation	Hypoxia upregulates StAR and aldosterone synthesis in pulmonary artery endothelial cells, promoting pulmonary vascular fibrosis
27006450	2016	Preclinical (mechanistic)	FASEB J	Aldosterone upregulates Raptor (mTORC1) in pulmonary artery smooth muscle cells, promoting PAH
35568141	2022	Preclinical (animal)	Cardiovasc Pathol	Eplerenone improved atrial remodelling induced by chronic intermittent hypoxia in rats
35346763	2022	Preclinical (animal)	Exp Gerontol	Chronic intermittent hypoxia induced renal fibrosis through MR activation
39707386	2024	Preclinical	Cell Commun Signal	Eplerenone reduced cirrhosis-associated changes in hepatocyte metabolism; hypoxia can activate MR

Australia Market Information

ARTG Number	Product Name	Dosage Form	Approved Indication
ARTG 13379E	Inpler	Tablet 50 mg	Not stated in the data compiled for this report

Safety Considerations

Contraindications flagged in the knowledge graph (not label text): liver disease, gallbladder disease, diabetic nephropathy, impaired renal function disease.
Drug Interactions: the interaction query returned 100 interacting drugs. Examples of Major interactions:
- Aprepitant
- Clarithromycin
- Clotrimazole
- Potassium chloride, potassium citrate and potassium bicarbonate (hyperkalaemia risk)
Moderate interactions include corticosteroids (hydrocortisone, prednisone, dexamethasone, betamethasone, budesonide, triamcinolone), aspirin, SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin), bupropion, miconazole, dronabinol and nabilone.

Please refer to the TGA-approved Product Information (PI) for the full warnings and contraindications.

Conclusion and Next Steps

Decision: Hold

Rationale: The TxGNN score is high (0.9950), but the supporting evidence is preclinical or indirect, with no registered clinical trials in pulmonary hypertension due to lung disease or hypoxia (Evidence Level L4). Safety label data are also unavailable, so this remains a research question rather than an actionable repurposing candidate.

To proceed, the following is needed:

Detailed mechanism of action data (MOA)
TGA Product Information warnings and contraindications for Inpler
Human clinical evidence (pilot or Phase 2 studies) in pulmonary hypertension due to lung disease or hypoxia
A hyperkalaemia and renal function monitoring plan, given the major interactions with potassium products and the renal contraindication signals
Confirmation of the approved indication text for the ARTG entry
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.