Therapy added to standard therapy including the use of β-blockers to reduce the risk of cardiovascular morbidity and morbidity in patients with stable left ventricular dysfunction (LVEF e≤40%) and clinical signs of after a recent heart attack. Therapy added to standard therapy to reduce the risk of cardiovascular morbidity and morbidity in adult patients with (chronic) heart failure (NYHA class II) and with left ventricular dysfunction (LVEF ≤30%).
Composition:
1 tabl powl. contains 25 mg or 50 mg eplerenone. The preparation contains lactose.
Action:
Aldosterone antagonist. Eplerenone has a relative binding specificity to recombinant human mineralocorticoid receptors compared to binding to recombinant human glucocorticoid, Progesterone and androgen receptors. It causes an increase in blood aldosterone and plasma renin activity, associated with a reduction of the inhibitory effect of aldosterone on renin secretion (regulation in the negative feedback mechanism). The resulting increased plasma renin activity and increased aldosterone levels do not reduce the effect of eplerenone. After oral administration, the maximum blood concentration of eplerenone occurs after 2 hours. The food has no effect on absorption. It binds approximately 50% of plasma proteins. It is metabolised by CYP3A4 and excreted in the urine (67%) and faeces (32%), mainly in the form of metabolites. T0,5 is 3-5 hours. Eplerenone is not eliminated by hemodialysis.
Contraindications:
Hypersensitivity to the components of the preparation. Potassium levels before treatment> 5 mmol / l. Severe renal failure, estimated glomerular filtration rate <30 ml / min / 1.73 m2 (EGFR). Severe hepatic impairment (Child-Pugh Class C). Concomitant use of potassium-sparing diuretics, potassium preparations or potent CYP3A4 inhibitors (such as Itraconazole, ketoconazole, ritonavir, nelfinavir, Clarithromycin, telithromycin and nefazodone). Combination therapy with ACE inhibitor and angiotensin receptor (ARB) antagonist and eplerenone.
Precautions:
Due to the risk of hyperkalemia, serum potassium should be monitored in all patients at the beginning of treatment and after dose adjustment. During continued treatment, periodic monitoring of potassium levels is particularly recommended in elderly patients with renal insufficiency or in patients with diabetes mellitus. The use of potassium preparations after initiation of eplerenone therapy is not recommended due to the increased risk of hyperkalemia. Reduction of eplerenone dose has been shown to reduce serum potassium. Addition of hydrochlorothiazide to eplerenone compensates for increases in serum potassium. Potassium levels should be monitored regularly in patients with impaired renal function and with microalbuminuria in the course of diabetes mellitus. Electrolyte concentration should be monitored in patients with mild or moderate hepatic impairment. The concomitant use of eplerenone with substances strongly inducing CYP3A4 is not recommended. Combined use with lithium, ciclosporin or tacrolimus should be avoided. Eplerenone should not be used together with concomitant therapy with an ACE inhibitor and an angiotensin receptor antagonist. Due to the lactose content, the preparation should not be used in patients with rare hereditary galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose. There are no data on the use of the preparation in children and adolescents.
Pregnancy and lactation:
Animal studies do not indicate any harmful effects of eplerenone on pregnancy, embryonal / fetal development, parturition and the development of a baby born - use with caution in pregnancy. The drug may pass into breast milk - due to the potential for side effects in breast-fed infants, a decision should be made to discontinue breast-feeding or discontinue the drug.
Orally. Adults: The starting dose is 25 mg once a day, then the dose should be gradually increased (within 4 weeks), controlling the level of potassium in the blood, up to a maintenance dose of 50 mg once a day. In patients with heart failure after a heart attack, eplerenone therapy should be started within 3-14 days after the diagnosis of acute myocardial infarction. After initiation of treatment, the dose should be adjusted according to serum potassium: <5 mmol / l - increase the dose from 25 mg every other day to 25 mg once a day, from 25 mg once a day to 50 mg once a day; 5-5,4 mmol / l - no dose change; 5.5-9.9 mmol / l - reduce the dose from 50 mg once a day to 25 mg once a day, from 25 mg once a day to 25 mg every other day, with 25 mg every other day to stop; ≥6 mmol / l - the drug should be discontinued. After discontinuation of eplerenone due to serum potassium ≥6.0 mmol / l, eplerenone may be re-initiated at a dose of 25 mg every other day when potassium levels fall below <5.0 mmol / l. Serum potassium should be measured prior to initiation of treatment with eplerenone, during the first week of treatment and one month after starting treatment or changing the dose, then periodically.Special groups of patients. No adjustment of the initial dose is required in patients with mild renal insufficiency, mild to moderate hepatic insufficiency, and in the elderly. In patients with moderate renal impairment (creatinine clearance 30-60 ml / min), the initial dose of 25 mg administered every other day should be adjusted depending on the potassium concentration. Lack of experience in patients with creatinine clearance <50 ml / min with heart failure after myocardial infarction - caution should be exercised. A dose of more than 25 mg once daily in patients with a creatinine clearance <50 ml / min has not been studied. When concomitant use of mild to moderate CYP3A4 inhibitors, eg Amiodarone, diltiazem and Verapamil, treatment should start with a 25 mg dose once a day; the dose should not exceed 25 mg once a day. The tablets can be taken regardless of meals.
(C)
