Eplerenone: Medical Uses, Administration, Side Effects, Contraindications, Interactions and Pharmacology

It is a steroidal antimineralocorticoid of the spironolactone group used as an adjunct in treating chronic heart failure.

It is classified as a selective aldosterone receptor antagonist (SARA), similar to diuretic spironolactone. However, it is much more demanding for the mineralocorticoid receptor in comparison (i.e., it has no antiandrogen, progestogen, glucocorticoid, or estrogen).

It is explicitly marketed to reduce cardiovascular risk in patients with myocardial infarction.

Eplerenone is a potassium-sparing diuretic, which means it helps the body eliminate water but retains potassium.

Eplerenone is chemically described as pregnant-4-ene-7,21-dicarboxylic acid, 9,11-epoxy-17-hydroxy-3-oxo-, γ-lactone, methyl ester, (7α, 11α, 17α) -. Its empirical formula is C24H30O6 and has a molecular weight of 414.50.

Medical uses of Eplerenone

Heart failure:

Eplerenone is specifically indicated for reducing the risk of cardiovascular death in people with heart failure and left ventricular dysfunction within 3-14 days after an acute myocardial infarction, in combination with standard therapies and as a treatment for hypertension.

A variant of the spironolactone group, Eplerenone, was developed to counter the depletion of the essential levels of potassium and magnesium that are common among other mineralocorticoid receptor antagonists. It is a more expensive alternative to spironolactone.

 

Hypertension:

Eplerenone can be used individually or with other medications to treat hypertension. Eplerenone effectively reduces blood pressure compared to spironolactone, enalapril, losartan, and amlodipine, but its effect on mortality remains unknown.

Central serous retinopathy:

Eplerenone is being explored as a treatment for central serous retinopathy. It is expected that, as an antimineralocorticoid, Eplerenone may inhibit the overactivation of the mineralocorticoid receptor pathway in the choroid.

Separate trials are being conducted to determine if there are beneficial effects of Eplerenone for acute and chronic central serous retinopathy.

Administration

This medicine is orally, usually once or twice a day, with or without food, or as directed by your doctor.

The dose is based on your medical condition ( high blood pressure, congestive heart failure), results of laboratory tests, and response to therapy. The medication can take up to 4 weeks to affect your blood pressure.

Adverse effects of aldosterone occur in the heart and brain due to changes in water retention and the excretion of sodium and potassium.

Side effects of Eplerenone

Common adverse reactions related to the use of Eplerenone include Headache, dizziness, diarrhea, stomach pain, nausea, cough, or flu-like symptoms (such as fever, chills, and unusual tiredness).

Eplerenone may have a lower incidence than the spironolactone of sexual side effects, such as feminization, gynecomastiaimpotence, intense sexual desire, and the reduction of the size of the male genitalia.

Tell your doctor immediately if you develop any of these rare but severe side effects:

  • Abnormal vaginal bleeding
  • Enlarged or painful breasts in men
  • Symptoms of elevated blood potassium levels (such as muscle weakness and slow/irregular heartbeat)

This is because other antimineralocorticoids have structural elements of the progesterone molecule, which causes progestogenic and antiandrogenic results. When taking these medications, it is essential to consider variations in their ability to compensate for the non-genomic effects of aldosterone.

Contraindications

Eplerenone is contraindicated in patients with hyperkalemia, severe renal insufficiency (creatinine clearance below 30 ml/min), or severe hepatic impairment (Child-Pugh C scale).

The manufacturer of Eplerenone also contraindicates concomitant treatment (with CC) with ketoconazole, itraconazole, or other potassium-sparing diuretics (although the manufacturer still considers these drugs to be CI). Potential benefits must be weighed against possible risks.

Interactions of eplerenone other medications

Eplerenone is metabolized primarily by the CYP3A4 enzyme of cytochrome P450. Therefore, there is the possibility of adverse drug interactions with other drugs that induce or inhibit CYP3A4.

Specifically, the concomitant use of potent CYP3A4 inhibitors ketoconazole and itraconazole is contraindicated. Other CYP3A4 inhibitors such as erythromycin, saquinavir, and verapamil should be used with caution.

Other medications that increase potassium levels may increase the risk of hyperkalemia associated with eplerenone therapy, including salt substitutes, potassium supplements, and other potassium-sparing diuretics.

Pharmacology

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 an affinity of 10 to 20 times lower for MRI than spironolactone and is less potent in vivo than an antimineralocorticoid.

However, unlike spironolactone, Eplerenone has little affinity for androgen, progesterone, and glucocorticoid receptors.

He has also more consistently observed non-genomic antimineralocorticoid effects of spironolactone.

Eplerenone differs from spironolactone in its extensive metabolism, with a short half-life and inactive metabolites.