|Synonyms||SC-66110; CGP-30083; 9-11α-Epoxymexrenone; 9,11α-Epoxy-7α-methoxycarbonyl-3-oxo-17α-pregn-4-ene-21,17-carbolactone|
|By mouth (tablets)|
|Protein binding||~50% (33–60%) (primarily to α1-acid glycoprotein)|
|Metabolites||6β-OH-EPL, 6β,21-OH-EPL, 21-OH-EPL, 3α,6β-OH-EPL (All inactive)|
|Elimination half-life||4–6 hours|
|Excretion||Urine (67%), feces (32%)|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||414.49 g·mol−1|
|3D model (JSmol)|
Eplerenone, sold under the brand name Inspra, is a steroidal antimineralocorticoid of the spirolactone group that is used as an adjunct in the management of chronic heart failure and high blood pressure, particularly for patients with resistant hypertension due to elevated aldosterone. Classed as a selective aldosterone receptor antagonist (SARA), it is similar to the diuretic spironolactone, though it is much more selective for the mineralocorticoid receptor in comparison (i.e., does not possess any antiandrogen, progestogen, glucocorticoid, or estrogenic effects), and is specifically marketed for reducing cardiovascular risk in patients following myocardial infarction. Eplerenone is a potassium-sparing diuretic, meaning that it helps the body get rid of water but still keep potassium.
It was patented in 1983 and approved for medical use in the United States in 2002. Eplerenone is currently approved for sale in the US, EU, Netherlands and Japan. Eplerenone costs an estimated $2.93 per day when treating congestive heart failure and $5.86 per day when treating hypertension.
Eplerenone is specifically indicated for the reduction of risk of cardiovascular death in people with heart failure and left ventricular dysfunction within 3–14 days of an acute myocardial infarction, in combination with standard therapies and as treatment against hypertension. A variant of the spirolactone group, Eplerenone was developed to contradict the depletion of essential potassium and magnesium levels that are common amongst other mineralocorticoid receptor antagonists. It is a more expensive alternative to spironolactone.
|Patients enrolled (n)||1663||6632|
|Population/Inclusion Criteria||NYHA Class III at the time of Enrollment||NYHA Class I-IV|
|Target Dose||50 mg/d||50 mg/d|
|Mean Dose Achieved||26 mg/d||43.5 mg/d|
|Mean duration of follow-up||24 mo||16 mo|
Eplerenone can be used individually or in combination with other medications to treat hypertension. In an 8-week trial with 417 patients with mild to moderate hypertension, eplerenone decreased systolic and diastolic blood pressure in a dose-dependent manner. Eplerenone effectively reduces blood pressure compared to agents such as spironolactone, enalapril, losartan and amlodipine, but its effect on mortality is still generally unknown. In mouse models, eplerenone has been shown to attenuate pulmonary hypertension, but not right heart failure.
For persons with resistant hypertension, aldosterone antagonists (including eplerenone) were safe and in comparative studies reduced systolic blood pressure by 24 mm Hg and diastolic blood pressure by about 8 mm Hg. Specifically, eplerenone is likely to be particularly effective in persons with resistant hypertension due to hyperaldosteronism, as indicated by a high blood plasma aldosterone and a low plasma renin activity.
Central serous retinopathy
Eplerenone is being explored as a treatment for central serous retinopathy. It is expected that as an antimineralocorticoid, eplerenone can inhibit over-activation of the mineralocorticoid receptor pathway in the choroid. Separate trials are underway to determine if there are beneficial effects of eplerenone for acute and chronic CSR.
Adverse effects of aldosterone occur in the heart and brain, due to changes in water retention and excretion of sodium and potassium. Common adverse drug reactions (ADRs) associated with the use of eplerenone include: hyperkalaemia, hypotension, dizziness, altered renal function, and increased creatinine concentration. Eplerenone may have a lower incidence than spironolactone of sexual side effects such as feminization, gynecomastia, impotence, low sex drive and reduction of size of male genitalia. This is because other antimineralocorticoids have structural elements of the progesterone molecule, causing progestogenic and antiandrogenic outcomes. When considering taking these medicines, it is important to note the variations in their ability to offset the nongenomic effects of aldosterone.
Eplerenone is contraindicated in patients with hyperkalaemia, severe renal impairment (creatinine Cl less than 30 ml/min), or severe hepatic impairment (Child-Pugh score C). The manufacturer of eplerenone also contraindicates ( relative C.I. ) concomitant treatment with ketoconazole, itraconazole or other potassium-sparing diuretics (though the manufacturer still considers taking these drugs to be absolute C.I.) Potential benefits should be weighted against possible risks.
Eplerenone is primarily metabolized by the cytochrome P450 enzyme CYP3A4. Thus the potential exists for adverse drug interactions with other drugs that induce or inhibit CYP3A4. Specifically, the concomitant use of the CYP3A4 potent inhibitors ketoconazole and itraconazole is contraindicated. Other CYP3A4 inhibitors including erythromycin, saquinavir, and verapamil should be used with caution. Other drugs that increase potassium concentrations may increase the risk of hyperkalemia associated with eplerenone therapy, including salt substitutes, potassium supplements and other potassium-sparing diuretics.
Eplerenone is an antimineralocorticoid, or an antagonist of the mineralocorticoid receptor (MR). Eplerenone is also known chemically as 9,11α-epoxy-7α-methoxycarbonyl-3-oxo-17α-pregn-4-ene-21,17-carbolactone and "was derived from spironolactone by the introduction of a 9α,11α-epoxy bridge and by substitution of the 17α-thoacetyl group of spironolactone with a carbomethoxy group." The drug controls high blood pressure by blocking the binding of aldosterone to the mineralocorticoid receptor (MR) in epithelial tissues, such as the kidney. Blocking the action of aldosterone decreases blood volume and lowers blood pressure. It has 10- to 20-fold lower affinity for the MR relative to spironolactone, and is less potent in vivo as an antimineralocorticoid. However, in contrast to spironolactone, eplerenone has little affinity for the androgen, progesterone, and glucocorticoid receptors. It also has more consistently observed non-genomic antimineralocorticoid effects relative to spironolactone (see membrane mineralocorticoid receptor). Eplerenone differs from spironolactone in its extensive metabolism, with a short half-life and inactive metabolites.
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- LoSalt Advisory Statement (PDF)
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