Pharmacological properties

Pharmacodynamics. eplerenon renders relative selectivity in linking with recombinant receptors of the person to mineralokortikoida in comparison with his interaction with recombinant receptors of the person to gks, to progesterone and androgens. eplerenon interferes with linking of receptors with Aldosteronum — important hormone system renin-angiotensin-aldosteronovoy which participates in regulation hell and it is involved in pathophysiological mechanisms of development of cardiovascular diseases.

to permanent increase in level of renin and Aldosteronum in blood plasma that demonstrates oppression of negative reversible impact of Aldosteronum on renin secretion. The increase in activity of renin and level of Aldosteronum in blood plasma resulting does not lead to oppression of action of an eplerenon.

data that addition of an eplerenon to the standard scheme of treatment at patients with chronic heart failure (class II-IV on classification of NYHA) leads to the expected dose-dependent increase in level of Aldosteronum Exist. Similarly and other data confirm increase in level of Aldosteronum and blocking of receptors to mineralokortikoida.

information that eplerenon reduces risk of a lethal outcome generally due to decline in mortality as a result of disturbances from a cardiovascular system Is available. There are no data on influence of an eplerenon on ChSS, duration of the QRS complex or intervals of PR and Q-T.

Pharmacokinetics. Absorption and distribution. The absolute bioavailability of an eplerenon is unknown. The C _max medicament in blood plasma is reached through 2 Parts C _max in blood plasma and AUC change in proportion to a dose in the range of 10-100 mg and is less proportional at use in a dose 100 mg. The equilibrium state comes within 2 days from an initiation of treatment. Meal does not influence medicament absorption. Eplerenon contacts proteins of blood plasma approximately for 50% and mainly contacts alpha 1-acid glycoproteins. The imaginary volume of distribution of an eplerenon in an equilibrium state is regarded as equal 50±7 l. Eplerenon is not inclined to linking with erythrocytes.

Metabolism and removal. Metabolism of an eplerenon is mainly carried out at the expense of CYP enzyme 3A4. In blood plasma of the person no active metabolites of an eplerenon are revealed. Less than 5% of a dose of an eplerenon are removed with urine and a stake in not changed look. After oral administration of a single dose it is radioactive marked medicament about 32% of a dose also about 67% are brought out of an organism with a stake — with urine. T _½ eplerenona makes about 3-5 h. The imaginary clearance is about 10 l/h of blood plasma

Use for patients of special groups

Age, sex and race. Significant differences in pharmacokinetics of an eplerenon at reception in a dose of 100 mg at men and women are not revealed. At elderly people in an equilibrium state noted increase in the _{levels C max} (22%) and AUC (45%) in comparison with patients of younger (18–45 years) of age. At patients of negroid race in an equilibrium condition of the C _max was 19% lower, and AUC — for 26% (see USE).

Renal failure. At patients with a severe form of a renal failure of AUC and C _max in an equilibrium state increase by 38 and 24% respectively. At the persons which are on a hemodialysis, these indicators are 26 lower and than 3% respectively. To correlation between clearance of an eplerenon in blood plasma and clearance of creatinine it is not established. Eplerenon is not brought at a hemodialysis (see. Special INSTRUCTIONS).

Liver failure. At use of an eplerenon in a dose of 400 mg at patients with moderate damages of a liver (class B on Chayld's classification — I Drink) the C _max and AUC of an eplerenon in an equilibrium state increase by 3.6 and 42% respectively (see USE).

Heart failure. At patients with heart failure (class II-IV on classification of NYHA) and AUC in an equilibrium state for 38 and 30% is higher than _{value C of max} , than at healthy volunteers of the corresponding age, body weight and a floor. There are data that the clearance of an eplerenon at patients with heart failure does not differ from clearance of this medicament at healthy volunteers of advanced age.

Indication

Addition to standard treatment using blockers of β-adrenoceptors for the purpose of the reduction of risk of incidence and mortality connected with cardiovascular diseases at stable patients with dysfunction of a left ventricle (fraction of emission of a left ventricle of 40%) and clinical signs of heart failure after recently postponed myocardial infarction.

Addition to standard optimum therapy for the purpose of reduction of risk of the incidence and mortality connected with cardiovascular diseases at adult patients with heart failure of the II class (chronic) on classification by NYHA and dysfunction of a left ventricle (fraction of emission of a left ventricle of 30%).

Drug release

in a dose 25 mg and 50 mg. the maximum daily dose makes 50 mg. eplerenon it is possible to accept both with food, and irrespective of meal (see pharmacokinetics).

Patients with heart failure after the postponed myocardial infarction. The recommended maintenance dose of an eplerenon makes 50 mg of 1 times a day. Treatment it is necessary to begin with a dose 25 mg of 1 times a day and to gradually increase to a target dose 50 mg of 1 times a day. It is desirable to reach this level of a dose for 4 weeks, considering potassium level in blood plasma (table). Treatment eplerenony needs usually to be begun in 3–14 days after an acute myocardial infarction.

Patients with heart failure of the II class (chronic) on classification of NYHA. Treatment of patients with chronic heart failure of the II class on classification of NYHA it is necessary to begin with a dose 25 mg of 1 times a day and to gradually increase to a target dose 50 mg of 1 times a day. It is desirable to reach this level of a dose for 4 weeks, considering potassium level in blood plasma (see the table and SPECIAL INSTRUCTIONS).

to Patients who have a potassium level in blood plasma 5 mmol/l should not begin treatment eplerenony (see CONTRAINDICATIONS).

potassium Level in blood plasma should be determined by

prior to treatment eplerenony, during the 1st week of treatment and in 1 month after the beginning of therapy or dose adjustment. If necessary it is necessary to determine periodically potassium level in blood plasma during treatment.

After an initiation of treatment a dose of medicament should be korrigirovat taking into account potassium concentration in blood plasma as it is specified in the table.

Dose adjustment after an initiation of treatment

Potassium concentration in blood plasma, mmol/l	Action	Dose adjustment
5.0	Increase	From 25 mg of 1 times in 2 days up to 25 mg of 1 times a day> From 25 mg of 1 times a day up to 50 mg of 1 times a day
5.0-5.4	Without changes	Dose is not changed
5.5-5.9	Decrease	With 50 mg of 1 times in day to 25 mg of 1 times in day With 25 mg of 1 times in day to 25 mg of 1 times in 2 days With 25 mg of 1 times on 2 days to temporary cancellation
6.0	Temporary cancellation	–

After temporary cancellation of an eplerenon because of increase in level of potassium to 6 mmol/l the resuming of treatment is possible in a dose of 25 mg of 1 times in 2 days after decrease in potassium concentration to the level of 5 mmol/l.

Patients of advanced age

For elderly people are not present need for correction of an initial dose of drug. Due to the age decrease in intensity of function of kidneys the risk of development of a hyperpotassemia at patients of advanced age increases. The risk can grow in addition in the presence of an associated disease which is followed by increase in system exposure of drug, in particular disturbances of functions of a liver of easy and moderate degree. It is recommended to carry out