Laylenon®

| Each tablet contains 25 mg or 50 mg of eplerenone, №30

PHARMACOLOGIC PROPERTIES
ATC Code: C03DA04, Aldosterone antagonists

Eplerenone has relative selectivity in binding to recombinant human mineralocorticoid receptors compared to its binding to recombinant human glucocorticoid, progesterone and androgen receptors. Eplerenone prevents the binding of aldosterone, a key hormone in the renin-angiotensin-aldosterone-system (RAAS), which is involved in the regulation of blood pressure and the pathophysiology of CV disease.

In dose-ranging studies of chronic heart failure (NYHA classification II-IV), the addition of eplerenone to standard therapy resulted in expected dose-dependent increases in aldosterone. Similarly, in a cardiorenal substudy of EPHESUS, therapy with eplerenone led to a significant increase in aldosterone. These results confirm the blockade of the mineralocorticoid receptor in these populations.

Eplerenone was studied in the EPHESUS. EPHESUS was a double-blind, placebo-controlled study, of 3 year duration, in 6632 subjects with acute MI, left ventricular dysfunction (as measured by left ventricular ejection fraction [LVEF] ≤40%), and clinical signs of heart failure. Within 3 to 14 days (median 7 days) after an acute MI, subjects received eplerenone or placebo in addition to standard therapies at an initial dose of 25 mg once daily and titrated to the target dose of 50 mg once daily after 4 weeks if serum potassium was < 5.0 mmol/L. During the study subjects received standard care including acetylsalicylic acid (92%), ACE inhibitors (90%), ß-blockers (83%), nitrates (72%), loop diuretics (66%), or HMG CoA reductase inhibitors (60%).

In EPHESUS, the co-primary endpoints were all-cause mortality and the combined endpoint of CV death or CV hospitalization; 14.4 % of subjects assigned to eplerenone and 16.7 % of subjects assigned to placebo died (all causes), while 26.7 % of subjects assigned to eplerenone and 30.0 % assigned to placebo met the combined endpoint of CV death or hospitalization. Thus, in EPHESUS, eplerenone reduced the risk of death from any cause by 15% (RR 0.85; 95% CI, 0.75-0.96; p= 0.008) compared to placebo, primarily by reducing CV mortality. The risk of CV death or CV hospitalization was reduced by 13% with eplerenone (RR 0.87; 95% CI, 0.79-0.95; p=0.002). The absolute risk reductions for the endpoints all cause mortality and CV mortality/hospitalization were 2.3% and 3.3%, respectively.

THERAPEUTIC INDICATIONS
Eplerenone is indicated:

1. In addition to standard therapy including beta-blockers, to reduce the risk of cardiovascular (CV) mortality and morbidity in stable patients with left ventricular dysfunction (LVEF ≤ 40 %) and clinical evidence of heart failure after recent myocardial infarction (MI).
2. In addition to standard optimal therapy, to reduce the risk of CV mortality and morbidity in adult patients with New York Heart Association (NYHA) class II (chronic) heart failure and left ventricular systolic dysfunction (LVEF ≤30%).