Ipleron, 50 mg 30 pcs.

Eplerenone

Indications

Myocardial infarction: in addition to standard therapy to reduce the risk of cardiovascular mortality and morbidity in patients with stable left ventricular dysfunction (ejection fraction less than 40%) and clinical signs of heart failure after myocardial infarction.

Chronic heart failure: in addition to standard therapy to reduce cardiovascular mortality and morbidity in patients with NYHA class II chronic heart failure with reduced left ventricular ejection fraction (<35%).

Pharmacological effect

Pharmacotherapeutic group: Diuretic potassium-sparing agent

Pharmacological action

Potassium-sparing diuretic. Eplerenone has relative selectivity for mineralocorticoid receptors in humans compared to glucocorticoid, progesterone and androgen receptors and prevents their binding to aldosterone, a key hormone of the RAAS, which is involved in the regulation of blood pressure and the pathogenesis of cardiovascular diseases.

Eplerenone causes a persistent increase in plasma renin and serum aldosterone levels. Subsequently, renin secretion is suppressed by aldosterone via a feedback mechanism. However, an increase in renin activity or circulating aldosterone levels does not affect the effects of eplerenone.

In patients with chronic heart failure of functional class II-IV according to the NYHA classification, the addition of eplerenone to standard therapy led to a predicted dose-dependent increase in aldosterone levels. A study examining cardiac and renal function in patients also found a significant increase in aldosterone levels as a result of eplerenone therapy. These data support blockade of mineralocorticoid receptors.

Pharmacokinetics

After oral administration of eplerenone at a dose of 100 mg, the absolute bioavailability is 69%. Cmax in blood plasma is achieved approximately 2 hours after oral administration. Cmax and AUC depend linearly on the dose in the range from 10 to 100 mg and nonlinearly at doses greater than 100 mg. Css is achieved within 2 days. Eating does not affect absorption.

The binding of eplerenone to plasma proteins is approximately 50%, predominantly with the alpha1-acid group of glycoproteins. The calculated Vd at equilibrium is 50 (±7) l. Eplerenone does not bind to red blood cells.

Metabolism of eplerenone is carried out mainly with the participation of the CYP3A4 isoenzyme. Active metabolites of eplerenone in blood plasma have not been identified.

T1/2 of eplerenone is about 3-5 hours, plasma clearance is approximately 10 l/hour. Less than 5% of the eplerenone dose is excreted unchanged by the kidneys and intestines. After a single oral dose of labeled eplerenone, about 32% of the dose was excreted through the intestines and about 67% through the kidneys.

Active ingredient

Eplerenone

Composition

Active substance: eplerenone

Pregnancy

There is no information on use during pregnancy. Use with caution and only in cases where the expected benefit to the mother significantly outweighs the possible risk to the fetus/child.

It is not known whether eplerenone is excreted into breast milk in humans. If use is necessary during lactation, breastfeeding should be discontinued.

Contraindications

Clinically significant hyperkalemia; serum potassium concentration at the beginning of treatment is more than 5 mmol/l; moderate or severe renal failure (creatinine clearance 2 mg/dl (or >177 mmol/l) in men or >1.8 mg/dl (or >159 mmol/l) in women; children and adolescents under 18 years of age; hypersensitivity to eplerenone.

Side Effects

Metabolism: often – hyperkalemia; uncommon – dehydration, hypercholesterolemia, hypertriglyceridemia, hyponatremia.

From the nervous system: often – dizziness; infrequently – headache, insomnia.

From the cardiovascular system: often – decreased blood pressure; uncommon – atrial fibrillation, myocardial infarction, left ventricular failure, orthostatic hypotension, thrombosis of the arteries of the lower extremities.

From the digestive system: often – diarrhea, nausea; infrequent – flatulence, vomiting.

From the hematopoietic system: uncommon – eosinophilia.

From the respiratory system: infrequently – pharyngitis.

From the skin: infrequently – increased sweating, itching.

From the musculoskeletal system: uncommon – back pain, cramps in the calf muscles of the legs.

From the kidneys and urinary tract: often – impaired renal function; infrequently – pyelonephritis.

General reactions: infrequently – asthenia, malaise.

Laboratory indicators: infrequently – increased levels of residual urea nitrogen, creatinine.

Interaction

Given the increased risk of hyperkalemia, eplerenone should not be prescribed to patients receiving potassium-sparing diuretics and potassium supplements. Potassium-sparing diuretics may enhance the effects of antihypertensive agents and other diuretics.

Cases of lithium toxicity have been described in patients receiving lithium in combination with diuretics and ACE inhibitors. Concomitant use of eplerenone and lithium should be avoided.

Cyclosporine and tacrolimus may cause renal dysfunction and increase the risk of hyperkalemia. Concomitant use of eplerenone and cyclosporine or tacrolimus should be avoided.

Treatment with NSAIDs can lead to acute renal failure due to direct suppression of glomerular filtration, especially in patients at risk (elderly patients and/or patients with dehydration). When using these drugs together, it is necessary to ensure adequate hydration and monitor renal function before and during treatment.

Concomitant use of trimethoprim with eplerenone increases the risk of developing hyperkalemia. It is recommended to monitor serum potassium concentrations and renal function, especially in patients with renal insufficiency and in elderly patients.

Eplerenone should be used with caution with ALP inhibitors or angiotensin II receptor antagonists. Such a combination may lead to an increased risk of developing hyperkalemia, especially in patients with impaired renal function, incl. in older people. Careful monitoring of renal function and serum potassium concentrations is recommended.

With simultaneous use of alpha1-blockers with eplerenone, the hypotensive effect may be enhanced and/or the risk of developing orthostatic hypotension may increase, and therefore it is recommended to monitor blood pressure when changing body position.

When used simultaneously with eplerenone, tricyclic antidepressants, neuroleptics, amifostine, baclofen may enhance the antihypertensive effect or increase the risk of developing orthostatic hypotension.

Concomitant use of glucocorticoids and tetracosactide with eplerenone may lead to a weakening of the antihypertensive effect (sodium and fluid retention).

The AUC of digoxin when used concomitantly with eplerenone increases by 16%. Caution must be exercised if digoxin is used at doses close to the maximum therapeutic dose.

No clinically significant pharmacokinetic interaction with warfarin has been identified. Caution must be exercised if warfarin is used in doses close to the maximum therapeutic dose.

When eplerenone is used with drugs that inhibit CYP3A4, significant pharmacokinetic interactions are possible. A potent inhibitor of CYP3A4 (ketoconazole 200 mg 2 times / day) caused an increase in eplerenone AUC by 441%. Concomitant use of eplerenone with strong CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin, telithromycin and nefazodone is contraindicated.

Concomitant use with erythromycin, saquinavir, amiodarone, diltiazem, verapamil and fluconazole was accompanied by significant pharmacokinetic interactions (the degree of increase in AUC ranged from 98% to 187%). When these drugs are used simultaneously with eplerenone, the dose of the latter should not exceed 25 mg.

Concomitant use of St. John’s wort tincture (a powerful CYP3A4 inducer) with eplerenone caused a decrease in the AUC of the latter by 30%. When using more potent inducers of CYP3A4, such as rifampicin, a more pronounced decrease in the AUC of eplerenone is possible. Given the possible decrease in the effectiveness of eplerenone, simultaneous use of strong CYP3A4 inducers (rifampicin, carbamazepine, phenytoin, phenobarbital, St. John’s wort tincture) is not recommended.

Manufacturer

Sinton Spain S.L., Spain