Manufacturer: G. D. Searle, Division of Pharmacia, Chicago, IL Indications: Eplerenone is intended for the treatment of hypertension and can be used alone or in combination with other antihypertensive agents.
Drug Class: Preg-4-ene-7, 21-dicarboxylic acid, 9,11-epoxy-17-hydroxy-3-oxo, gamma-lactone methyl ester (7a, 11a, 17a) selectively blocks aldosterone, a key component within the renin-angiotensin aldosterone system (RAAS). The RAAS plays an important role in the body’s regulation of the cardiovascular system.
Uniqueness of Drug: Eplerenone selectively blocks aldosterone binding at the mineralocorticoid receptor. Al-dosterone synthesis, which occurs in the adrenal gland, is modulated by multiple factors, including angiotensin II and non-RAAS mediators such as adrenocorticotropic hormone (ACTH) and potassium. Aldosterone binds to mineralocorticoid receptors in both epithelial (e.g., kidney) and nonepithelial (e.g., heart, blood vessels, and brain) tissues and increases blood pressure through induction of sodium reabsorption and possibly by other mechanisms. Eplerenone has been shown to produce sustained increases in plasma renin and serum aldosterone levels, consistent with inhibition of the negative regulatory feedback of aldosterone on renin secretion. The resultant increased plasma renin activity and aldosterone-circulating concentrations do not overcome the effect of eplerenone on blood pressure.
Precautions: The principal risk associated with eplerenone is hyperkalemia, which can cause serious, sometimes fatal, arrhythmias. This risk can be minimized by careful patient selection, avoidance of certain concomitant treatments, and follow-up. Periodic monitoring is recommended in patients at risk for the development of hyperkalemia, including patients who are receiving concomitant angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists, until the effect of eplerenone is established.
Dosage and Administration: The recommended starting dose is 50 mg of eplerenone, administered once daily. Its full therapeutic effect is apparent within four weeks. For patients with inadequate blood pressure response, the dosage should be increased to 50 mg twice daily. Higher doses are not recommended, because they are no more effective than a 100-mg dose and because they are associated with an increased risk of hyperkalemia. Eplerenone may be used either alone or in combination with other antihypertensive drugs.
P&T Committee Considerations: Despite the availability of several key classes of compounds, control of hypertension has remained inadequate. Eplerenone is the first agent designed to selectively block the hormone aldosterone in the treatment of high blood pressure, and it is expected to provide treatment benefits in a broad range of patients. Eplerenone represents an important new treatment option that goes beyond standard therapies in targeting the aldosterone pathway, which contributes to the development and progression of hypertension. Aldosterone is a key component within the RAAS and plays a significant role in regulating the cardiovascular system.
Clinical trials involving approximately 3,000 patients have demonstrated that eplerenone tablets effectively lower high blood pressure, both alone and in combination with other anti-hypertensive therapies. The drug has been generally well tolerated and should be placed on the formulary for the treatment of hypertension.
Eplerenone tablets have not yet been placed on the market and have not been priced.