Espiro, 25 mg 30 pcs

Espiro is a potassium-saving diuretic.

Pharmic action: Eplerenone has relative selectivity for mineralocorticoid receptors in humans compared to glucocorticoid, progesterone, and androgen receptors and blocks their binding to aldosterone, a key hormone of the renin-angiotensin-aldosterone system (RAAS) that is involved in blood pressure regulation and the pathogenesis of cardiovascular disease.

Eplerenone causes a persistent increase in plasma renin and serum aldosterone levels. Subsequently, renin secretion is inhibited by aldosterone through a feedback mechanism. At the same time, increase of renin activity or circulating aldosterone level does not affect the effects of eplerenone.

Pharmacokinetics:

absorption and distribution.

The absolute bioavailability of eplerenone is not known. Maximum plasma concentration is reached approximately 2 h after administration. The maximum plasma concentration (Cmax) and area under the concentration curve (AUC) are proportional to the dose in the range of 10-100 mg and less proportional when used in doses greater than 100 mg. The equilibrium concentration is reached within 2 days. Food intake has no effect on absorption.

Binding of eplerenone to plasma proteins is about 50%, mainly due to binding to alpha 1-acid glycoproteins. The apparent volume of distribution in the equilibrium state is 50 (±7) liters. Eplerenone has no selective binding to erythrocytes.

Metabolism and excretion.

The metabolism of eplerenone is carried out by the CYP3A4 isoenzyme of cytochrome P-450. Active metabolites of eplerenone have not been identified in human plasma.
Less than 5% of the dose of eplerenone is excreted unchanged in the urine and feces. After a single oral dose of the drug labeled with the radioactive isotope, about 32% of the dose was excreted in the feces and about 67% in the urine. The elimination phase elimination half-life of eplerenone is about 3-5 hours. Clearance in blood plasma is about 10 l/h.

Special groups of patients.

Age, sex and race:

The pharmacokinetics of eplerenone in men and women were not significantly different. Equilibrium Cmax (22%) and AUC (45%) were increased in elderly patients compared to younger patients (18-45 years). Equilibrium Cmax and AUC were decreased by 19% and 26%, respectively, in non-Hispanic individuals.

Renal insufficiency:

The pharmacokinetics of eplerenone were studied in patients with renal failure of varying severity and in patients on hemodialysis. Compared with healthy patients, equilibrium AUC and Cmax increased by 38 and 24%, respectively, in patients with severe renal failure, and decreased by 26 and 3%, respectively, in patients on hemodialysis. No correlation was found between eplerenone plasma clearance and creatinine clearance. Eplerenone is not eliminated by hemodialysis.

Help failure:

Eplerenone has not been studied in patients with severe hepatic impairment, so its use is contraindicated in this group of patients.

Heart failure:

Eplerenone clearance in patients with heart failure is similar to that of healthy individuals.

Indications

An adjunctive agent to standard therapy with beta-adrenoblockers to reduce the risk of mortality and cardiovascular morbidity in patients with stable clinical condition with left ventricular heart dysfunction (LVEF [left ventricular ejection fraction] ≤40%; to reduce the risk of mortality and cardiovascular morbidity in patients with clinical manifestations of heart failure after a recent myocardial infarction.

Active ingredient

Composition

Tablets

Active ingredient:

Eplerenone 25 mg.

Lactose monohydrate,

microcrystalline cellulose,

hypromellose,

sodium lauryl sulfate,

croscarmellose sodium,

magnesium stearate,

Cosmetics:

Opadray Yellow 33G32578, including: hypromellose, titanium dioxide (E171), lactose monohydrate, macrogol, triacetin, iron (III) oxide yellow (E172).

How to take, the dosage

Espiro can be taken with or independently of meals.

The recommended maintenance dose of Espiro is 50 mg once daily. The maximum daily dose is 50 mg.

In order to reduce the risk of mortality and cardiovascular morbidity in patients with clinical manifestations of heart failure after a recent myocardial infarction, treatment should be started with a dose of 25 mg once daily and gradually increased, preferably over 4 weeks, until the desired dose of 50 mg once daily is reached, monitoring serum potassium levels (see Table 1). Usually it is reasonable to start Espiro treatment within 3-14 days after diagnosis of myocardial infarction.

. In order to reduce the risk of mortality and cardiovascular morbidity in patients with stable clinical condition with left ventricular heart dysfunction (LVEF [left ventricular ejection fraction] ≤40%) in chronic heart failure (NYHA class II), treatment starts with a dose of 25 mg once daily and gradually increases it, best over 4 weeks, until reaching the required dose of 50 mg once daily, controlling serum potassium levels (see Table 1).

Patients whose serum potassium concentration is >5.0 mmol/L should not be started on Espiro.

The serum potassium level should be determined before the start of treatment with the drug, during the first week and one month after the start of use or dose adjustment. Thereafter, serum potassium levels should be monitored periodically as needed.

When Espiro is discontinued due to increase of serum potassium concentration ≥ 6.0 mmol/l, reapplication of the drug at a dose of 25 mg is possible in a day if serum potassium concentration is less than 5.0 mmol/l.

Application in children and adolescents.

There are no data on the use of eplerenone in children, so the use of the drug in this group of patients is not recommended.

Application in the elderly

There is no need to adjust the starting dose in the elderly. Due to age-related impairment of renal function, the risk of hyperkalemia is higher in the elderly. It may be further increased due to concomitant diseases that increase the concentration of the drug product in the body, especially mild or moderate hepatic impairment. Periodic monitoring of serum potassium levels is recommended.

Application in patients with renal impairment.

The initial dose adjustment in patients with mild renal impairment is not required. Periodic monitoring of serum potassium levels is recommended.
Eplerenone is not removable by dialysis.

Application in patients with hepatic impairment.
Adjustment of the initial dose in patients with mild to moderate hepatic impairment is not required. In view of increased eplerenone concentrations in such patients, it is recommended to monitor serum potassium concentrations frequently and regularly, especially in elderly patients.

Application in patients taking other drugs.
When concomitant use of weak or moderate CYP3A4 inhibitors, e.g., amiodarone, diltiazem and verapamil, treatment should be started with a dose of 25 mg once daily. The dose should not exceed 25 mg once daily.

Contraindications

Side effects

Hyperkalemia, dizziness, syncope, arterial hypotension, cough, diarrhea, nausea, constipation, rash, itching, impaired renal function.

Infrequent (>1/1,000 to – pyelonephritis, eosinophilia, hypothyroidism, hyponatremia, dehydration, hypercholesterolemia, hypertriglyceridemia, insomnia, headache, hypoesthesia, myocardial infarction, left ventricular heart failure, atrial fibrillation, tachycardia, lower extremity artery thrombosis, orthostatic hypotension, pharyngitis, vomiting, flatulence, increased sweating, back pain, painful cramps of the calf muscles, cholecystitis, gynecomastia, asthenia, malaise, increased levels of urea nitrogen, creatinine, blood glucose, reduced levels of epidermal growth factor receptor.

Frequency not known: angioedema.

Similarities