P&T Portfolio - Eplerenone

November 18, 2002

Eplerenone - For use in patients with hypertension

 

HEALTH-SYSTEM EDITION
P&T PORTFOLIO

Generic name

Eplerenone

Proprietary name/manufacturer

Inspra/Pharmacia

FDA-approved indication

Eplerenone is approved for the treatment of hypertension when used alone or in combination with other antihypertensive agents.

Pharmacology

Eplerenone is a selective aldosterone receptor antagonist similar in structure to spironolactone. It binds to the mineralocorticoid receptor and blocks the binding of aldosterone, a component of the renin-angiotensin-aldosterone system (RAAS). Aldosterone synthesis, which occurs primarily in the adrenal gland, is modulated by multiple factors, including angiotensin II and non-RAAS mediators such as ACTH and potassium. Aldosterone binds to mineralocorticoid receptors in both epithelial and nonepithelial tissues and increases blood pressure through induction of sodium reabsorption and possibly other mechanisms. The affinity of eplerenone for the aldosterone receptor is less than that of spironolactone. However, eplerenone exhibits less affinity than spironolactone for other steroid receptors, which may reduce adverse effects such as gynecomastia and menstrual irregularities.

Pharmacokinetics

 

Efficacy

Protein binding50%
Volume of distribution43-90 L
MetabolismPrimarily mediated via CYP450 3A4. No active metabolites identified
ExcretionUrine (67%) Feces (32%)
Half-life (terminal)4-6 hours

Several controlled clinical trials involving more than 3,000 patients have demonstrated the efficacy of eplerenone for the treatment of hypertension when used alone or in combination with other antihypertensive agents. In these studies, eplerenone significantly reduced systolic and diastolic blood pressure in patients with mild to moderate hypertension, compared with placebo, and demonstrated sustained efficacy over a 24-hour period. Blood pressure lowering was apparent within two weeks of therapy, with maximal antihypertensive effects achieved within four weeks. Eplerenone has been used in combination with ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, beta-blockers, and hydrochlorothiazide. Eplerenone appears to be similar in efficacy to spironolactone, but more study is needed.

Contraindications

• Serum potassium > 5.5 mEq/L

• Type 2 diabetes with microalbuminuria

• Serum creatinine > 2.0 mg/dl in males or > 1.8 mg/dl in females

• Creatinine clearance < 50 ml/min

• Potassium supplements or potassium-sparing diuretics (amiloride, spironolactone, or triamterene)

• Strong inhibitors of CYP450 3A4 (e.g., ketoconazole, itraconazole)

Warnings

• Eplerenone may cause hyperkalemia, which can lead to serious, sometimes fatal, arrhythmias. The rates of hyperkalemia increase with decreasing renal function.

Adverse effects

The most common adverse effects of eplerenone, occurring in 1% to 3% of patients include: abdominal pain, albuminuria, coughing, diarrhea, fatigue, flu-like symptoms, hypercholesterolemia, hypertriglyceridemia, and vaginal bleeding.

Dose

Initial dose is 50 mg p.o. once daily. It may be increased to 50 mg p.o. twice daily.

Conclusion/comments

Eplerenone is a selective aldosterone receptor antagonist that has demonstrated efficacy when used alone or in combination with other antihypertensive agents for the treatment of mild to severe hypertension. Aldosterone plays an important role in the pathophysiology of left ventricular hypertrophy (LVH), which is associated with a significant increase in cardiovascular morbidity and mortality in patients with hypertension. A large phase III trial is under way investigating eplerenone for the treatment of heart failure.

Published November 2002. The content is based on medical literature and product information available at that time.

 

 



P&T Portfolio - Eplerenone.

Drug Topics

2002;22:HSE20.