QuickView for Eplerenone (compound)

Summary
General Info

PubChem

PubChem Compound 443872

Name:	eplerenone
PubChem Compound ID:	443872
Molecular formula:	C₂₄H₃₀O₆
Molecular weight:	414.491 g/mol
Synonyms:	CGP-30083; 107724-20-9; Eplerenone; Inspra; D01115; Epoxymexrenone; SC-66110; C12512; Eplerenone (JAN/USAN); Inspra (TN)

DrugBank

Identification

Name:	eplerenone
Name (isomeric):	DB00700
Drug Type:	small molecule
Synonyms:	Epoxymexrenone
Brand:	INSPRA
Category:	Aldosterone Antagonists, Antihypertensive Agents
CAS number:	107724-20-9

Pharmacology

Indication:	For improvement of survival of stable patients with left ventricular systolic dysfunction (ejection fraction <40%) and clinical evidence of congestive heart failure after an acute myocardial infarction.
Pharmacology:	Eplerenone, an aldosterone receptor antagonist similar to spironolactone, has been shown to produce sustained increases in plasma renin and serum aldosterone, consistent with inhibition of the negative regulatory feedback of aldosterone on renin secretion. The resulting increased plasma renin activity and aldosterone circulating levels do not overc... show more » Eplerenone, an aldosterone receptor antagonist similar to spironolactone, has been shown to produce sustained increases in plasma renin and serum aldosterone, consistent with inhibition of the negative regulatory feedback of aldosterone on renin secretion. The resulting increased plasma renin activity and aldosterone circulating levels do not overcome the effects of eplerenone. Eplerenone selectively binds to recombinant human mineralocorticoid receptors relative to its binding to recombinant human glucocorticoid, progesterone and androgen receptors. show less «
Mechanism of Action:	Eplerenone binds to the mineralocorticoid receptor and thereby blocks the binding of aldosterone (component of the renin-angiotensin-aldosterone-system, or RAAS). Aldosterone synthesis, which occurs primarily in the adrenal gland, is modulated by multiple factors, including angiotensin II and non-RAAS mediators such as adrenocorticotropic hormone (... show more » Eplerenone binds to the mineralocorticoid receptor and thereby blocks the binding of aldosterone (component of the renin-angiotensin-aldosterone-system, or RAAS). Aldosterone synthesis, which occurs primarily in the adrenal gland, is modulated by multiple factors, including angiotensin II and non-RAAS mediators such as adrenocorticotropic hormone (ACTH) and potassium. Aldosterone binds to mineralocorticoid receptors in both epithelial (e.g., kidney) and nonepithelial (e.g., heart, blood vessels, and brain) tissues and increases blood pressure through induction of sodium reabsorption and possibly other mechanisms. show less «
Absorption:	The absolute bioavailability of eplerenone is unknown.
Protein binding:	50%
Biotransformation:	Eplerenone is metabolized primarily by CYP3A4, however, no active metabolites have been identified in human plasma.
Half Life:	4-6 hours
Clearance:	Apparent plasma cl=10 L/hr
Toxicity:	The most likely symptoms of human overdosage would be anticipated to be hypotension or hyperkalemia. However, no cases of human overdosage with eplerenone have been reported.
Affected organisms:	Humans and other mammals

Interactions

Drug interaction:

Clarithromycin	The macrolide, clarithromycin, may increase the effect and toxicity of eplerenone.
Telithromycin	Telithromycin may reduce clearance of Eplerenone. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Eplerenone if Telithromycin is initiated, discontinued or dose changed.
Verapamil	This CYP3A4 inhibitor increases the effect and toxicity of eplerenone
Itraconazole	Itraconazole may increase the effect and toxicity of eplerenone.
Nefazodone	Nefazodone increases the effect and toxicity of eplerenone

Clarithromycin	The macrolide, clarithromycin, may increase the effect and toxicity of eplerenone.
Telithromycin	Telithromycin may reduce clearance of Eplerenone. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Eplerenone if Telithromycin is initiated, discontinued or dose changed.
Verapamil	This CYP3A4 inhibitor increases the effect and toxicity of eplerenone
Itraconazole	Itraconazole may increase the effect and toxicity of eplerenone.
Nefazodone	Nefazodone increases the effect and toxicity of eplerenone
Ketoconazole	Ketoconazole, a CYP3A4 inhibitor, may increase the effect and toxicity of eplerenone.
Voriconazole	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of eplerenone by decreasing its metabolism. Concomitant therapy is contraindicated.
Erythromycin	This CYP3A4 inhibitor increases the effect and toxicity of eplerenone
Amiloride	Increased risk of hyperkalemia. Monitor serum potassium levels during concomitant threapy.
Trandolapril	Increased risk of hyperkalemia. Monitor serum potassium levels.
Lithium	Eplerenone increases serum levels of lithium
Nelfinavir	The protease inhibitor, nelfinavir, may increase the effect and toxicity of eplerenone.
Conivaptan	CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eplerenone. The combination of eplerenone with any strong CYP3A4 inhibitor is contraindicated.
Potassium	This association presents an increased risk of hyperkalemia
Polystyrene sulfonate	Risk of alkalosis in renal impairment
Fluconazole	This CYP3A4 inhibitor increases the effect and toxicity of eplerenone
Spironolactone	This association presents an increased risk of hyperkalemia
Saquinavir	This CYP3A4 inhibitor increases the effect and toxicity of eplerenone
Triamterene	This association presents an increased risk of hyperkalemia
Troleandomycin	The macrolide, troleandomycin, may increase the effect and toxicity of eplerenone.
Treprostinil	Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Ritonavir	This protease inhibitor, ritonavir, may increase the effect and toxicity of eplerenone.
Bicalutamide	CYP3A4 Inhibitors like bicalutamide may increase the serum concentration of eplerenone. A lower starting dose of eplerenone (25 mg once daily) is recommended in patients with hypertension who are also taking drugs that are moderate inhibitors of CYP3A4.

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Targets

Mineralocorticoid receptor

Enzymes

Cytochrome P450 3A4

Cytochrome P450 3A5

Cytochrome P450 3A7

Cytochrome P450 11B2, mitochondrial