Renial 25mg 30 tablets — Made in Ukraine — Free Delivery

Brand: Kyivmedpreparat
Product Code: Renial 25mg
Availability: In Stock

$28.81

Description

Pharmacological properties

Pharmacodynamics. Eplerenone has a relative selectivity in binding to recombinant human mineralocorticoid receptors compared to its interaction with recombinant human receptors for corticosteroids, progesterone, and androgens. eplerenone interferes with the binding of receptors to aldosterone, an important hormone of the renin-angiotensin-aldosterone system, which is involved in the regulation of blood pressure and is involved in the pathophysiological mechanisms of the development of cardiovascular diseases.

The use of eplerenone leads to a persistent increase in the level of renin and aldosterone in the blood plasma, which indicates the inhibition of the negative reversible effect of aldosterone on the secretion of renin. The resulting increase in renin activity and aldosterone levels in blood plasma does not inhibit the action of eplerenone.

There is evidence that the addition of eplerenone to the standard treatment regimen in patients with chronic heart failure (NYHA class II – IV) leads to the expected dose-dependent increase in aldosterone levels. Similarly, other data support increased aldosterone levels and blockade of mineralocorticoid receptors.

Eplerenone has been reported to reduce the risk of death primarily by reducing mortality from cardiovascular disorders. There is no evidence of the effect of eplerenone on heart rate, the duration of the QRS complex, or the P – R and Q – T intervals.

Pharmacokinetics. Absorption and distribution. The absolute bioavailability of eplerenone is unknown. Cmax of the preparation in blood plasma is achieved after 2 hours. Cmax in blood plasma and AUC change in proportion to the dose in the range of 10–100 mg and less proportionally when used at a dose of 100 mg. The equilibrium state occurs within 2 days from the start of treatment. Food intake does not affect the absorption of the preparation. Eplerenone binds to plasma proteins by about 50% and binds mainly to alpha-1-acid glycoproteins. The apparent volume of distribution of eplerenone at equilibrium is considered to be 50 ± 7 liters. Eplerenone does not tend to bind to red blood cells.

Metabolism and excretion. Eplerenone is metabolized primarily by the CYP 3A4 enzyme. No active metabolites of eplerenone have been identified in human plasma. Less than 5% of a dose of eplerenone is excreted unchanged in the urine and feces. After oral administration of a single dose of a radioactively labeled preparation, approximately 32% of the dose is excreted in the feces and approximately 67% in the urine. T1 / 2 of eplerenone is about 3-5 hours. The apparent clearance from blood plasma is approximately 10 l / h.

Use in special groups of patients

Age, gender and race. There were no significant differences in the pharmacokinetics of eplerenone when taken at a dose of 100 mg in men and women. In the elderly in the equilibrium state, there was an increase in the levels of Cmax (22%) and AUC (45%) compared with patients of younger (18–45 years) age. In patients of the Negroid race in the equilibrium state, the Cmax was lower by 19%, and the AUC - by 26% (see APPLICATION).

Renal failure In patients with severe renal failure, the AUC and Cmax at steady state increase by 38 and 24%, respectively. In persons on hemodialysis, these indicators are lower by 26 and 3%, respectively. No correlation has been established between plasma clearance of eplerenone and creatinine clearance. Eplerenone is not excreted during hemodialysis (see SPECIAL INSTRUCTIONS).

Liver failure. When eplerenone is used at a dose of 400 mg in patients with moderate liver damage (class B according to the Child-Pugh classification), the Cmax and AUC of eplerenone at steady state increase by 3.6 and 42%, respectively (see APPLICATION).

Heart failure. In patients with heart failure (NYHA class II – IV), steady state Cmax and AUC values are 38% and 30% higher than in healthy volunteers of the corresponding age, body weight and gender. There is evidence that the clearance of eplerenone in patients with heart failure does not differ from the clearance of this preparation in healthy elderly volunteers.

Indications

Addition to standard therapy with β-adrenergic receptor blockers to reduce the risk of morbidity and mortality associated with cardiovascular disease in stable patients with left ventricular dysfunction (left ventricular ejection fraction 40%) and clinical signs of heart failure after recent myocardial infarction ...

Adjunct to standard optimal therapy to reduce the risk of morbidity and mortality associated with cardiovascular disease in adult patients with NYHA Class II (chronic) heart failure and left ventricular dysfunction (left ventricular ejection fraction 30%).

Contraindications

Hypersensitivity to eplerenone or to any of the other preparation excipients;

serum potassium> 5 mmol / L at the start of treatment;

severe renal failure (estimated glomerular filtration rate <30 ml / min / 1.73 m2);

severe hepatic impairment (class C according to the Child-Pugh classification);

treatment with potassium-sparing diuretics, potassium supplements, or potent CYP3A4 inhibitors (eg, itraconazole, ketoconazole, ritonavir, nelfinavir, clarithromycin, telithromycin, and nefazodone) (see Preparation Interactions) and other interactions

the simultaneous use of eplerenone in a triple combination together with an ACE inhibitor and an angiotensin receptor blocker.

Application features

Hyperkalemia. During treatment with eplerenone, according to its mechanism of action, hyperkalemia may develop. In all patients, at the beginning of treatment and when changing the dose of the preparation, the level of potassium in the blood serum should be monitored. In the future, it is recommended to carry out periodic monitoring, especially in patients at risk of hyperkalemia (such as elderly patients, patients with renal insufficiency (see section "Dosage and Administration") and patients with diabetes mellitus). Potassium supplements are not recommended after starting treatment with eplerenone due to the increased risk of hyperkalemia. Reducing the dose of eplerenone leads to a decrease in the concentration of potassium in the blood serum. There is evidence that the additional use of hydrochlorothiazide in the treatment of eplerenone compensates for the increase in serum potassium concentration.

When eplerenone is used in combination with an ACE inhibitor and / or an angiotensin receptor blocker, the risk of hyperkalemia may be increased. Eplerenone should not be used simultaneously in a triple combination with an ACE inhibitor and an angiotensin receptor blocker (see sections "Contraindications" and "Interaction with other preparations and other forms of interaction").

Renal dysfunction. In patients with impaired renal function (including diabetic microalbuminuria), potassium levels should be monitored regularly. Decreased renal function is associated with an increased risk of hyperkalemia. Although the results of the EPHESUS study in patients with type 2 diabetes and microalbuminuria are limited, an increased incidence of hyperkalemia was observed in this small group of patients. Eplerenone is not cleared by hemodialysis.

Liver dysfunction. In patients with mild to moderate impaired liver function (classes A and B according to the Child-Pugh classification), an increase in serum potassium levels of more than 5.5 mmol / l is not observed. These patients need to have their electrolyte levels monitored. The use of eplerenone for the treatment of patients with severe renal impairment has not been studied, therefore eplerenone is contraindicated for use in such patients (see sections "Contraindications" and "Dosage and Administration"). CYP3A4 inductors. The simultaneous use of eplerenone and powerful inducers of CYP3A4 is not recommended (see the section "Interaction with other medicinal products and other forms of interaction").

Lithium, cyclosporine, tacrolimus should not be prescribed during treatment with eplerenone (see section "Interaction with other medicinal products and other forms of interaction"). Fertility There is no information on the effect on human fertility.

Lactose. The preparation contains lactose, so it should not be prescribed to patients with rare hereditary disorders (galactose intolerance, Lapp lactase deficiency, or glucose and galactose malabsorption syndrome).

Application during pregnancy or lactation.

Pregnancy. There is no adequate data on the use of eplerenone in pregnant women.

The information obtained in the course of animal studies does not indicate a direct or indirect adverse effect on the course of pregnancy, the development of the embryo and fetus, childbirth and postpartum development. Caution should be exercised when administering eplerenone to pregnant women.

Breastfeeding period. It is not known whether eplerenone passes into human breast milk after oral administration. At the same time, data from preclinical studies indicate the presence of eplerenone and / or its metabolites in the milk of rats and the normal development of offspring that have experienced the effect of eplerenone in this way.

Since the potential for side effects in breastfed infants has not been investigated, a clinical decision should be made to discontinue breastfeeding or discontinue the preparation, depending on the importance of the preparation to the mother.

The ability to influence the reaction rate when driving vehicles or other mechanisms.

Studies of the effect of eplerenone on the ability to drive vehicles or other mechanisms have not been conducted. Eplerenone does not cause drowsiness or impaired cognitive functions, but when driving or using other mechanisms, the possibility of dizziness developing during preparation treatment should be taken into account.

Application

The preparation is available in a dose of 25 mg and 50 mg. the maximum daily dose is 50 mg. eplerenone can be taken with or without food (see Pharmacokinetics).

Patients with heart failure after myocardial infarction. The recommended maintenance dose of eplerenone is 50 mg once daily. Treatment should begin with a dose of 25 mg once a day and gradually increase to a target dose of 50 mg once a day. It is desirable to achieve this dose level in 4 weeks, taking into account the level of potassium in the blood plasma (table). Eplerenone should usually be started 3–14 days after acute myocardial infarction.

Patients with NYHA class II (chronic) heart failure. Patients with NYHA Class II chronic heart failure should begin treatment with a dose of 25 mg once daily and gradually increase to the target dose of 50 mg once daily. It is desirable to achieve this dose level in 4 weeks, taking into account the level of potassium in the blood plasma (see table and SPECIAL INSTRUCTIONS).

Patients with a plasma potassium level of 5 mmol / L should not start treatment with eplerenone (see CONTRAINDICATIONS).

Plasma potassium levels should be determined prior to initiation of eplerenone treatment, during the 1st week of treatment, and 1 month after initiation of therapy or dose adjustment. If necessary, you should periodically determine the level of potassium in the blood plasma during the treatment period.

After starting treatment, the dose of the preparation should be adjusted taking into account the concentration of potassium in the blood plasma, as indicated in the table.

Dose adjustments after starting treatment

Plasma potassium concentration, mmol / l	Action	Dose adjustment
five	Enhancement	From 25 mg once every 2 days to 25 mg once a day From 25 mg once a day to 50 mg once a day
5.0-5.4	Without changes	Do not change the dose
5.5-5.9	Decrease	From 50 mg once a day to 25 mg once a day From 25 mg once a day to 25 mg once every 2 days From 25 mg 1 time for 2 days until temporary cancellation
6	Temporary cancellation	–

After temporary discontinuation of eplerenone due to an increase in potassium levels up to ³ 6 mmol / l, treatment can be resumed at a dose of 25 mg once every 2 days after the potassium concentration has dropped to below 5 mmol / l.

Elderly patients.

For elderly patients, there is no need to adjust the initial dose of the preparation. Due to the age-related decrease in the intensity of renal function, the risk of developing hyperkalemia in elderly patients increases. The risk may be further increased in the presence of a concomitant disease, which is accompanied by an increase in systemic exposure to the preparation, in particular, mild to moderate hepatic dysfunction. It is recommended to periodically monitor the level of potassium in the blood serum (see the section "Peculiarities of use").

Renal dysfunction.

Patients with mild renal impairment do not require adjustment of the initial dose.

It is recommended to periodically monitor the level of potassium in the blood serum (see section "Peculiarities of use") and adjust the dose of the preparation in accordance with the table above.

Patients with moderate renal impairment (creatinine clearance 30-60 mg / ml) should start treatment with a dose of 25 mg once every 2 days and adjust the dose of the preparation depending on the potassium concentration (see table above). It is recommended to periodically monitor the level of potassium in the blood serum (see the section "Peculiarities of use").

There is no experience of using the preparation in patients with creatinine clearance <50 ml / min and heart failure after myocardial infarction. Eplerenone should be used with caution in these patients.

The use of doses exceeding 25 mg per day in patients with creatinine clearance <50 ml / min has not been investigated.

Eplerenone is contraindicated in patients with severe renal impairment (creatinine clearance <30 ml / min) (see section "Contraindications"). Eplerenone is not cleared from the body through dialysis.

Liver dysfunction.

Patients with mild or moderate hepatic impairment do not require adjustment of the initial dose, however, due to an increase in the level of systemic exposure of eplerenone in this category of patients, and especially in elderly patients, it is recommended to carry out frequent and regular monitoring of the concentration of potassium in the blood serum (see section "Peculiarities of use").

Combined use.

In the case of simultaneous use with weak or moderate inhibitors of CYP3A4 (for example, amiodarone, diltiazem and verapamil), eplerenone can be started with an initial dose of 25 mg once a day. The dose of the preparation should not exceed 25 mg once a day (see the section "Interaction with other medicinal products and other types of interactions").

Children.

There is no data on the use of eplerenone in children, therefore, the use of the preparation in this group of patients is not recommended.

Overdose

There have been no reports of adverse reactions associated with overdose of eplerenone in humans. It is expected that the most likely manifestations of an overdose in humans will be arterial hypotension or hyperkalemia. Eplerenone cannot be cleared from the body by hemodialysis. Eplerenone binds effectively to activated carbon. If arterial hypotension develops, supportive treatment should be initiated. If hyperkalemia develops, treatment should be initiated according to standards.

Side effects

In two studies (EPHESUS and EMPHASIS-HF), it was demonstrated that the overall incidence of adverse reactions with the use of eplerenone and placebo was the same.

The following are adverse reactions that may have been associated with eplerenone that occurred more frequently with eplerenone than with placebo, or serious adverse reactions that occurred with eplerenone more often than with placebo, or that were reported in the course of post-marketing surveillance.

Adverse reactions are classified by organ systems and by absolute frequency: very often (≥ 1/10), often (≥ 1/100 - <1/10), infrequently (≥ 1/1000 - <1/100), rarely (≥ 1 / 10000 - <1/1000), very rare (<1/10000), unknown (cannot be determined based on available information).

Infections and invasions: infrequently: infection, pyelonephritis, pharyngitis.

On the part of the blood and lymphatic system: infrequently - eosinophilia.

From the endocrine system: infrequently - hypothyroidism.

Disorders of metabolism and digestion: often - hyperkalemia (see sections "Contraindications" and "Peculiarities of use"), hypertriglyceridemia; infrequently - hyponatremia, dehydration, hypercholesterolemia.

From the side of the psyche: infrequently - insomnia.

From the nervous system: often - dizziness, syncope, headache; infrequently - hypesthesia.

From the side of the heart: often - left ventricular failure, atrial fibrillation; infrequently - tachycardia.

On the part of the vascular system: often - hypotension; infrequently - thrombosis of the arteries of the extremities, orthostatic hypotension.

From the respiratory system, chest and mediastinal organs: often - cough.

From the gastrointestinal tract: often - diarrhea, nausea, constipation, vomiting; infrequently - bloating.

On the part of the skin and subcutaneous tissues: often - rash, itching; infrequently - hyperhidrosis, angioedema.

From the musculoskeletal system and connective tissue: often - muscle spasms, back pain; infrequently - pain in the musculoskeletal system.

From the side of the kidneys and urinary tract: often - impaired renal function (see sections "Interaction with other preparations and other types of interactions" and "Peculiarities of use").

From the liver and biliary tract: infrequently - cholecystitis.

From the reproductive system and mammary glands: infrequently - gynecomastia.

General disorders and disorders at the injection site: infrequently - asthenia, malaise.

Laboratory tests: often - increased blood urea, increased creatinine levels; infrequently - a decrease in the number of epidermal growth factor receptors, an increase in blood glucose levels.

In the EPHESUS study, more strokes were reported numerically in patients ≥ 75 years of age. At the same time, there was no statistically significant difference in the incidence of strokes between the eplerenone (30) and placebo (22) groups. In the EMPHASIS-HF study, the number of strokes in patients ≥ 75 years of age was 9 in the eplerenone group and 8 in the placebo group.

Reporting suspected adverse reactions.

Reports of suspected adverse reactions following preparation registration are important. This allows continuous monitoring of the balance between the benefits and risks of using the preparation. Healthcare professionals are asked to report any suspected adverse reactions in accordance with local requirements

Shelf life

3 years from the date of manufacture in bulk.

Storage conditions

Store in original packaging at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

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