Eplerenone (eplerenone)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Eplerenone is considered a relatively selective competitive mineralocorticoid (aldosterone) receptor antagonist.
Although eplerenone shares many of the pharmacologic effects of spironolactone, eplerenone is considered a relatively selective mineralocorticoid (aldosterone) receptor antagonist, whereas spironolactone is nonselective. Eplerenone binds selectively to mineralocorticoid receptors and has low (less than 1%) affinity for glucocorticoid, progesterone, and androgen receptors. The steroid-related adverse effects (e.g., gynecomastia, impotence, menstrual abnormalities) occur less frequently with eplerenone than with spironolactone.
Aldosterone binds to mineralocorticoid receptors in both epithelial (e.g., kidney, salivary glands, GI tract) and nonepithelial (e.g., heart, blood vessels, brain) tissues and increases blood pressure through induction of sodium reabsorption, vascular remodeling, endothelial dysfunction, and possibly other mechanisms. Limited data indicate that increased serum aldosterone concentrations within the physiologic range may predispose individuals to the development of hypertension. Eplerenone is a competitive antagonist of aldosterone at mineralocorticoid receptors in the kidney, myocardium, salivary gland, GI tract, brain, and vasculature and the drug has been shown to inhibit the physiologic effects of aldosterone in these organs.
Some of the antihypertensive effects of eplerenone may be related to restoration of endothelial function by increasing the release of nitric oxide, which results in vasodilation. Eplerenone has been shown to produce sustained increases in plasma renin and serum aldosterone concentrations, reflecting the inhibition of the negative feedback of aldosterone on renin secretion. The resulting increased plasma renin activity and circulating aldosterone concentrations do not overcome the antihypertensive effects of eplerenone.
Eplerenone appears to have cardioprotective effects in patients with congestive heart failure and left ventricular dysfunction following myocardial infarction (MI). The exact mechanism of the cardioprotective action of eplerenone in such patients has not been fully elucidated, but it appears to be related more to the drug's ability to competitively inhibit the pathophysiologic effects of aldosterone on the myocardium than to its hypotensive effects. In animals, aldosterone stimulates coronary inflammation and causes myocardial and coronary perivascular fibrosis and ventricular hypertrophy or remodeling.
Eplerenone reduces coronary vascular inflammation, the risk of subsequent development of interstitial myocardial and coronary perivascular fibrosis, cardiac hypertrophy, and/or ventricular remodeling.
Eplerenone is extensively metabolized in the liver, principally via the cytochrome P-450 (CYP) 3A4 isoenzyme to inactive metabolites. The absolute bioavailability of eplerenone is 69% after oral administration of a 100-mg tablet. Steady-state concentrations of the drug are attained within 2 days with repeat dosing.
Less than 5% of an eplerenone dose is recovered unchanged in the urine and feces. Approximately 67 and 32% of an orally administered dose of eplerenone is excreted in urine and feces, respectively.
USES: This medication is used to treat high blood pressure. Lowering high blood pressure helps prevent strokes, heart attacks and kidney problems. It works by blocking a chemical (aldosterone) in your body which in turn lowers the amount of sodium and water the body retains.
It is also used to treat heart failure following a heart attack.
Generic name: eplerenone
Pronunciation: (eh-PLER-en-own)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
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Indications
The following indications are listed for Eplerenone:
- Chronic Heart Failure Following Myocardial Infarction
- Hypertension
Also known as: Chf Following Mi, Congestive Heart Failure Resulting From Myocardial Infarction, Elevated Blood Pressure, Essential Hypertension, Hyperpiesia, Hyperpiesis, Hypertensive Disorder, Systemic Arterial Hypertension.
Dosing
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No dosing information is available for this tab.
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Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Eplerenone is contraindicated in patients with serum potassium concentrations exceeding 5.5 mEq/L at initiation of therapy, in those with creatinine clearance of 30 mL/minute or less, and in those receiving concomitant therapy with potent inhibitors of cytochrome P-450 (CYP) isoenzyme 3A4 (e.g., ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir) or any agent described as a potent CYP3A4 inhibitor in its prescribing information.
In addition, when used for hypertension, the drug is contraindicated in patients with type 2 diabetes mellitus with microalbuminuria; serum creatinine concentrations exceeding 2 or 1.8 mg/dL in males or females, respectively; creatinine clearance less than 50 mL/minute; and in those receiving potassium supplements or potassium-sparing diuretics (e.g., amiloride, spironolactone, triamterene).
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects occurring in 2% or more of patients receiving eplerenone for the management of congestive heart failure following acute MI, but occurring at greater incidence in patients receiving the drug than in those receiving placebo, include hyperkalemia, increased serum creatinine concentrations, urinary tract disorders, adverse CNS effects, and adverse GI effects.
Adverse effects reported in 1% or more of patients receiving eplerenone for the management of hypertension are dizziness, fatigue, flu-like symptoms, cough, diarrhea, abdominal pain, hyperkalemia, decreased serum sodium concentrations, abnormal vaginal bleeding, gynecomastia, hypercholesterolemia, hypertriglyceridemia, mastodynia, or albuminuria.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy have not been established in children younger than 18 years of age. For information on overall principles and expert recommendations for treatment of hypertension in pediatric patients, see Uses: Hypertension in Pediatric Patients, in the Thiazides General Statement 40:28.20.
Category B. (See Users Guide.)
Eplerenone is distributed into milk in rats; a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.
No substantial differences in safety and efficacy have been observed in geriatric patients relative to younger adults. Geriatric patients 75 years of age and older with congestive heart failure following an acute MI did not benefit from the addition of eplerenone to standard medical therapy. Because geriatric patients may have decreased renal function (reduced creatinine clearance), the incidence of hyperkalemia may be increased in geriatric patients (65 years of age and older). (See Endocrine, Electrolyte, and Metabolic Effects under Warnings/Precautions: Warnings, in Cautions.)
ICD codes
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Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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