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 antagonist, originally used to treat hypertension. The TxGNN model predicts it may be effective for pulmonary hypertension owing to lung disease and/or hypoxia, but there are currently no registered clinical trials and only 14 publications, mostly preclinical or indirect, supporting this direction.

Quick Overview

Item	Content
Original Indication	Hypertension (hypertensive disorder)
Predicted New Indication	Pulmonary hypertension owing to lung disease and/or hypoxia
TxGNN Prediction Score	0.9950
Evidence Level	L5
Canada Market Status	Marketed (marketed DINs: 6 of 6)
Number of DINs	6 (marketed: 6)
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, 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 (MR) antagonist. Its efficacy in hypertension is established, and mechanistically it may be applicable to pulmonary hypertension driven by hypoxia.

Preclinical studies link chronic intermittent hypoxia to MR activation, renal fibrosis and atrial remodelling, and eplerenone attenuated these effects in rodent models. Laboratory work also suggests hypoxia raises aldosterone production in pulmonary artery endothelial cells and promotes pulmonary vascular fibrosis. In rat models of pulmonary arterial hypertension, MR antagonists, including eplerenone, improved pulmonary vascular remodelling. A small clinical study in patients with obstructive sleep apnoea and resistant hypertension also suggests eplerenone may reduce apnoea severity and arterial stiffness.

Together these findings support a plausible hypoxia–MR–vascular remodelling axis. However, none of them directly measures pulmonary arterial pressure or pulmonary hypertension outcomes in humans. The high TxGNN score is a computational prediction, not clinical validation.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
27230560	2016	Clinical study	Pol Arch Med Wewn	Eplerenone in OSA with resistant hypertension; assessed effect on OSA severity and arterial stiffness (small study, indirect endpoints)
41483355	2026	Review	Curr Hypertens Rep	Reviews OSA-driven hypertension and evidence for aldosterone blockade as a tailored treatment
15199296	2004	Review	Curr Opin Nephrol Hypertens	Glucocorticoids can activate the mineralocorticoid receptor in non-epithelial cells, contributing to hypertension
35043674	2022	Preclinical (rat)	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	BMC Pulm Med	Eplerenone attenuated pulmonary vascular remodelling more than right ventricular remodelling in PAH
25001622	2014	Preclinical	Circulation	Hypoxia upregulates StAR and aldosterone synthesis in pulmonary artery endothelial cells, promoting vascular fibrosis
27006450	2016	Preclinical	FASEB J	Aldosterone raises Raptor (mTORC1) in pulmonary artery smooth muscle cells, promoting PAH
35568141	2022	Preclinical (rat)	Cardiovasc Pathol	Eplerenone improved atrial remodelling induced by chronic intermittent hypoxia
35346763	2022	Preclinical (rat)	Exp Gerontol	Chronic intermittent hypoxia induced renal fibrosis through MR activation
39707386	2024	Preclinical	Cell Commun Signal	Eplerenone reduced cirrhosis-associated changes in hepatocyte glucose and lipid metabolism, with hypoxia-driven MR activation

Canada Market Information

DIN	Product Name	Dosage Form	Approved Indication
02543397	JAMP EPLERENONE	Not specified	Not specified
02323060	INSPRA	Not specified	Not specified
02323052	INSPRA	Not specified	Not specified
02471442	MINT-EPLERENONE	Not specified	Not specified
02543389	JAMP EPLERENONE	Not specified	Not specified

A sixth authorization, MINT-EPLERENONE (DIN 02471450), is also valid. All six are single-ingredient products.

Safety Considerations

Disease-level contraindication signals (from the knowledge graph, not label text): liver disease, gallbladder disease, diabetic nephropathy, and impaired renal function disease.
Drug Interactions: 100 interactions were identified. Major-level examples include:
- Aprepitant
- Clarithromycin
- Clotrimazole
- Potassium chloride, potassium citrate and potassium bicarbonate (hyperkalaemia risk)
Moderate-level examples include corticosteroids (hydrocortisone, dexamethasone, prednisone, and others), SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin), acetylsalicylic acid, bupropion, and miconazole.
Other considerations: Hyperkalaemia and renal-function risk would need careful assessment in any new patient population, particularly those with renal impairment.

Conclusion and Next Steps

Decision: Hold

Rationale: Evidence for pulmonary hypertension is indirect, consisting mainly of animal and cell studies plus a small sleep apnoea study with different endpoints. No clinical trials are registered. The high TxGNN score is a prediction only, so this remains a research question rather than a candidate ready for development.

To proceed, the following is needed:

Human data measuring pulmonary arterial pressure or pulmonary hypertension outcomes, ideally from a pilot or Phase 2 trial
Mechanism of action data compiled in a structured form
Package insert warnings and contraindications from Health Canada, including approved indication text and dosage forms for each DIN
A safety plan covering hyperkalaemia, renal impairment, and the major drug interactions listed above
Disclaimer

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