Eplerenone, sold under the brand name Inspra, is an

aldosterone antagonist An antimineralocorticoid, also known as a mineralocorticoid receptor antagonist (MRA or MCRA) or aldosterone antagonist, is a diuretic drug which antagonizes the action of aldosterone at mineralocorticoid receptors. This group of drugs is often u ...

type of potassium-sparing diuretic that is used to treat

chronic heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

and

high blood pressure Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

, particularly for patients with resistant hypertension due to elevated

aldosterone Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a c ...

. It is a

steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...

al antimineralocorticoid of the spirolactone group and a

selective aldosterone receptor antagonist An antimineralocorticoid, also known as a mineralocorticoid receptor antagonist (MRA or MCRA) or aldosterone antagonist, is a diuretic drug which receptor antagonist, antagonizes the action of aldosterone at mineralocorticoid receptors. This group ...

(SARA). Eplerenone is more selective than spironolactone at the mineralocorticoid receptor relative to binding at androgen,

progestogen Progestogens, also sometimes written progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestogen in the body. ...

, glucocorticoid, or estrogen receptors.

Medical uses

Heart failure

Eplerenone reduces risk of death in patients with heart failure, particularly in patients with recent myocardial infarction (heart attack).

Hypertension

Eplerenone lowers blood pressure in patients with primary hypertension. Eplerenone also reduces arterial stiffness and vascular endothelial dysfunction. For persons with resistant hypertension, eplerenone is safe and effective for reducing blood pressure, particularly in persons with resistant hypertension due to

hyperaldosteronism Hyperaldosteronism is a medical condition wherein too much aldosterone is produced by the adrenal glands, which can lead to lowered levels of potassium in the blood (hypokalemia) and increased hydrogen ion excretion (alkalosis). This cause of min ...

Central serous chorioretinopathy

Eplerenone is often prescribed for people with central serous chorioretinopathy (CSC). However, the most recent and largest randomized controlled trial showed that eplerenone has no significant effect on chronic CSC.

Adverse effects

Common adverse drug reactions (ADRs) associated with the use of eplerenone include: hyperkalaemia, hypotension, dizziness, and reduced renal clearance. Eplerenone may have a lower incidence than spironolactone of sexual side effects such as

feminization Feminization most commonly refers to: * Feminization (biology), the hormonally induced development of female sexual characteristics * Feminization (activity), a sexual or lifestyle practice where a person assumes a female role * Feminization (soci ...

, gynecomastia, impotence, low sex drive and reduction of size of male genitalia. This is because other antimineralocorticoids have structural elements of the

progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...

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. Currently, there is not enough evidence available from the randomized controlled trials on side effects of eplerenone to do a benefit versus risk assessment in people with primary hypertension.

Interactions

Eplerenone is primarily metabolized by the

cytochrome P450 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...

enzyme

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...

. 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 Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen and antifungal medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous candid ...

and itraconazole is contraindicated. Other CYP3A4 inhibitors including

erythromycin Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used duri ...

, 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.

Pharmacology

Eplerenone is an antimineralocorticoid, or an

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

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

to the mineralocorticoid receptor (MR) in epithelial tissues, such as the kidney. Blocking the action of

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,

, and glucocorticoid receptors. It also has more consistently observed non-genomic antimineralocorticoid effects relative to spironolactone (see

membrane mineralocorticoid receptor Membrane mineralocorticoid receptors (mMRs) or membrane aldosterone receptors are a group of receptors which bind and are activated by mineralocorticoids such as aldosterone. Unlike the classical nuclear mineralocorticoid receptor (MR), which media ...

). Eplerenone differs from spironolactone in its extensive metabolism, with a short half-life and inactive metabolites. Eplerenone seems to be about 50 to 75% as potent as spironolactone as an antimineralocorticoid. Hence, 25 mg/day spironolactone may be equivalent to approximately 50 mg/day eplerenone.

Regulatory and Patent History

Eplerenone was patented in 1983 and approved for medical use in the United States in 2002. Eplerenone is currently approved for sale in Canada, 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 Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

References

{{Mineralocorticoid receptor modulators Antimineralocorticoids Epoxides Lactones Methyl esters Pfizer brands Pregnanes Spirolactones