Eplerenone-Teva (Eplerenone-Teva)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
Read on
Active substanceEplerenoneEplerenone
Similar drugsTo uncover
  • Inspra®
    pills inwards 
    Pfizer Inc.     USA
  • Eplerenone-Teva
    pills inwards 
    Teva Pharmaceutical Enterprises Co., Ltd.     Israel
  • Espiro
    pills inwards 
    Pharmaceutical factory "POLFARMA" JSC     Poland
    • Dosage form: & nbspTfilm-covered abeys.
    Composition:

    1 tablet contains:

    active substance: eplerenone 25.00 mg / 50.00 mg;

    Excipients: lactose monohydrate 38.20 mg / 76.40 mg, cellulose microcrystalline 19.60 mg / 39.20 mg, crospovidone 2.55 mg / 5.10 mg, sodium lauryl sulfate 0.85 mg / 1.70 mg, talc 0.85 mg / 1.70 mg, magnesium stearate 0.45 mg / 0.90 mg;

    film sheath: Opadrai II 85F23987 orange 3.00 mg / 6.00 mg (polyvinyl alcohol 1.20 mg / 2.40 mg, titanium dioxide (E 171) 0.6522 mg / 1.3044 mg, macrogol-3350 0.606 mg / 1.212 mg, talc 0.444 mg /0.888 mg, ferric iron oxide yellow (E 172) 0.093 mg / 0.186 mg, iron oxide red (E 172) 0.0048 mg / 0.0096 mg).

    Description:

    Dosage of 25 mg. Rhomboid, biconvex tablets, covered with a film shell from yellow to brownish-yellow color, engraved "E25" on one side.

    Dosage of 50 mg. Diamond-shaped, biconvex tablets, covered with a film coating from yellow to brownish-yellow color, engraved "E50" on one side.
    Pharmacotherapeutic group:diuretic potassium-sparing agent
    ATX: & nbsp

    C.03.D.A.04   Eplerenone

    Pharmacodynamics:

    Eplerenone - a potassium-sparing diuretic, an aldosterone antagonist, binds with mineralocorticoid receptors with high selectivity. Virtually does not affect glucocorticoid, progesterone and androgen receptors. Prevents the binding of mineralocorticoid receptors to aldosterone, the key hormone of the renin-angiotensin-aldosterone system (RAAS), which is involved in the regulation of blood pressure (BP) and the pathogenesis of cardiovascular diseases.

    Eplerenone causes a persistent increase in renin concentration in plasma and aldosterone in the blood serum. Subsequently, renin secretion is suppressed by aldosterone by the feedback mechanism. In this case, an increase in the activity of renin or the concentration of circulating aldosterone does not affect the effects of eplerenone.

    It is able to reduce left ventricular hypertrophy and its dysfunction in individuals with clinical signs of heart failure.

    Electrocardiography

    Eplerenone does not affect the heart rate (heart rate), changes in the duration of intervals QRS, PR or QT not identified.

    Pharmacokinetics:

    Suction and distribution

    Absolute bioavailability of eplerenone is 69% after taking 100 mg of eplerenone orally in the form of tablets. The maximum concentration in the blood plasma (CmOh) is reached after about 2 hours. FROMmOh and the area under the pharmacokinetic curve (AUC) linearly depend on the dose in the range from 10 to 100 mg and non-linearly - in a dose of more than 100 mg. The equilibrium state is reached within 2 days. Eating does not affect absorption.

    Eplerenone is approximately 50% bound to blood plasma proteins, predominantly with the alpha-1-acid group of glycoproteins. The calculated volume of the distribution in the equilibrium state is 50 (± 7) l. Eplerenone does not bind to erythrocytes.

    Metabolism and excretion

    Metabolism of eplerenone is carried out mainly under the action of isoenzyme CYP3A4. Active metabolites of eplerenone in human blood plasma are not identified.

    In an unchanged form, less than 5% of the dose of eplerenone is excreted through the kidneys and intestine. After a single ingestion of labeled eplerenone, about 32% of the dose was excreted through the intestine and about 67% through the kidneys. The half-life of eplerenone is about 3-5 hours, the clearance from the blood plasma is about 10 l / h.

    Special Groups

    Age, gender and race: the pharmacokinetics of eplerenone at a dose of 100 mg once a day was studied in elderly patients (over 65 years), men and women. The pharmacokinetics of eplerenone did not differ significantly between men and women. In an equilibrium state in elderly patients CmOh and AUC were respectively 22% and 45% higher than in young patients (18-45 years of age).

    Renal insufficiency

    The pharmacokinetics of eplerenone have been studied in patients with renal insufficiency of varying severity and in patients on hemodialysis. In comparison with patients of the control group, in patients with severe renal insufficiency, there was an increase in the equilibrium AUC and CmOh by 38% and 24% respectively, and in patients on hemodialysis - their decrease by 26% and 3%. Correlations between the clearance of eplerenone from plasma and the clearance of creatinine were not detected. Eplerenone not removed during hemodialysis.

    Liver failure

    The pharmacokinetics of eplerenone at a dose of 400 mg were compared in patients with impaired liver function of moderate severity (7-9 points according to the Child-Pugh classification) and healthy volunteers. Equilibrium CmOh and AUC eplerenone were increased by 3.6% and 42%, respectively. In patients with severe hepatic insufficiency eplerenone was not studied, therefore its use in this group of patients is not shown.

    Heart failure

    The pharmacokinetics of eplerenone in a dose of 50 mg were studied in patients with heart failure (II-IV FC). Equilibrium AUC and CmOh in patients with heart failure were respectively 38 and 30% higher than in healthy volunteers, matched for age, body weight and sex. The eplerenone's clearance in patients with heart failure is similar to that of healthy elderly people.

    Indications:

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

    - Chronic heart failure: in addition to standard therapy, in order to reduce the risk of cardiovascular mortality and morbidity in patients with chronic cardiac insufficiency II functional class by classification NYHA, with left ventricular dysfunction (ejection fraction <35%).

    Contraindications:

    - Hypersensitivity to eplerenone or other components of the drug;

    - clinically significant hyperkalemia;

    - serum potassium concentration at the beginning of treatment> 5.0 mmol / l;

    - renal failure of moderate or severe severity - creatinine clearance (CK) <30 ml / min in patients with CHF beginning with II FC according to classification NYHA;

    - hepatic insufficiency of severe degree (more than 9 points according to the Child-Pugh classification);

    - simultaneous reception of potassium-sparing diuretics, potassium preparations or potent inhibitors of isoenzyme CYP3A4, for example, itraconazole, ketoconazole, ritonavir, nelfinavir, clarithromycin, telithromycin and nefazodone (see "Interactions with Other Drugs"):

    - rare hereditary intolerance to galactose, lactase deficiency, glucose-galactose malabsorption syndrome (see section "Special instructions").

    Experience with the drug in children under the age of 18 years is not, therefore, its purpose patients of this age group are not recommended.

    Carefully:

    - Diabetes mellitus type 2 and microalbuminuria (see section "Special instructions");

    - elderly age;

    - impaired renal function (QC less than 50 ml / min);

    - simultaneous use of eplerenone and ACE inhibitors or angiotensin II receptor antagonists;

    - strong isoenzyme inducers CYP3A4;

    - preparations containing lithium;

    - cyclosporin or tacrolimus;

    - digoxin and warfarin in doses close to the maximum therapeutic (see sections "Special instructions" and "Interaction with other drugs").

    Do not use a triple combination of an ACE inhibitor and angiotensin II receptor antagonists with eplerenone.

    Pregnancy and lactation:

    There is no information on the use of the drug in pregnant women. The drug should be used with caution and only in those cases where the expected benefit to the mother significantly exceeds the possible risk to the fetus.

    Information on the removal of eplerenone after ingestion with breast milk is not. Possible adverse effects of eplerenone on newborns who are breastfed are unknown, so it is advisable to either stop breastfeeding or to cancel the drug, depending on the importance of its use for the mother.

    Dosing and Administration:

    Inside.

    Eating does not affect the absorption of the drug Eplerenone-Teva. Dosages of 25 and 50 mg can be used for individual dose selection.

    Myocardial infarction

    Treatment should begin with a dose of 25 mg once a day and increase it to 50 mg once a day after 4 weeks, taking into account the potassium concentration in the serum (see Table I). The recommended maintenance dose of the drug is 50 mg once a day.

    Chronic heart failure, starting with II functional class

    Treatment should also begin with a dose of 25 mg once a day and increase it to 50 mg once a day after 4 weeks, taking into account the potassium concentration in the blood serum (see Table 1).

    Table 1. Selection of dose after treatment

    Concentration of potassium in blood serum (mmol / l)

    Act

    Dose change

    <5,0

    Increase in dose

    with 25 mg every other day to 25 mg once daily

    with 25 mg once daily to 50 mg once daily

    5,0-5,4

    Maintenance dose

    The dose remains the same

    5,5-5,9

    Dose reduction

    with 50 mg once daily to 25 mg once daily

    with 25 mg once daily to 25 mg every other day

    with 25 mg every other day - temporary withdrawal of the drug

    ≥6,0

    Abolition of the drug

    Not applicable

    After a temporary discontinuation of the drug due to an increase in serum potassium concentration ≥ 6.0 mmol / L, the drug can be treated withresume at a dose of 25 mg every other day, when the serum potassium concentration is <5.0 mmol / l.

    General recommendations

    The concentration of potassium in blood serum should be determined before the appointment of the drug, during the first week and 1 month after the initiation of therapy or when the dose of the drug is changed. In the future, it is also necessary to periodically monitor the potassium concentration in the blood serum.

    Elderly patients

    Correction of the starting dose in elderly patients is not required. In connection with the age-related decrease in renal function in elderly patients, the risk of hyperkalemia increases, especially in the presence of concomitant diseases that increase the concentration of eplerenone in the blood serum, in particular, in the violation of liver function from mild to moderate severity. It is recommended to periodically determine the concentration of potassium in the blood serum (see section "Special instructions").

    Impaired renal function

    Correction of the starting dose in patients with impaired renal function of mild severity is not required. The degree of hyperkalemia increases with impaired renal function. It is recommended to periodically determine the concentration of potassium in the serum (see below).section "Special instructions").

    Eplerenone is not removed during hemodialysis.

    In patients with impaired renal function of severe degree (CK <30 ml / min), the use of the drug is contraindicated.

    In patients with CHF beginning with II FK and renal dysfunction of moderate severity (CK 30-60 ml / min), therapy should be started from a dose of 25 mg every other day, followed by dose adjustment depending on the potassium concentration in the blood serum.

    Experiments with eplerenone in patients with heart failure after myocardial infarction and KK <50 ml / min have not been performed. It is necessary to use with caution the drug Eplerenone-Teva in such patients.

    In patients with SC <50 ml / min, the use of the drug Eplerenone-Teva at a dose above 25 mg once a day has not been investigated (see also the sections "Contraindications" and "Special instructions").

    Impaired liver function

    Correction of the starting dose in patients with impaired liver function from mild to moderate severity is not required. Given the increased concentration of eplerenone in such patients, it is recommended that the serum potassium concentration be monitored regularly, especially in elderly patients (see section "Special instructions").The use of the drug Eplerenone-Teva in patients with impaired liver function is contraindicated.

    Concomitant therapy

    With the simultaneous use of drugs that have a weak or moderately expressed inhibitory effect on the isoenzyme CYP3A4, for example: erythromycin, saquinavir, amiodarone, diltiazem, verapamil and fluconazole, - treatment with Eplerenone-Teva can be started at a dose of 25 mg once a day, with the dose of the latter not exceeding 25 mg once a day (see section "Interaction with other drugs").

    Side effects:

    Adverse reactions are classified with the following frequency: very often (≥1 / 10): often - (≥1 / 100 to <1/10); infrequently - (≥1 / 1000 to <1/100); frequency is unknown (adverse reactions in the post-marketing period: the reaction can not be estimated from available data).

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

    Metabolic and nutritional disorders: often - hyperkalemia, hypercholesterolemia, hypertriglyceridemia: infrequently - dehydration, hyponatremia, hypothyroidism.

    Mental disorders: infrequently - insomnia.

    Neurological disorders: often - dizziness, fainting; infrequently: headache, hypoesthesia.

    From the heart: often - myocardial infarction; infrequently - atrial fibrillation, left ventricular failure.

    Vascular disorders: often - lowering blood pressure; infrequently - orthostatic hypotension, thrombosis of the arteries of the lower extremities.

    On the part of the respiratory system, thorax and mediastinum: often - cough; infrequently pharyngitis.

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

    From the liver and biliary tract: infrequently - cholecystitis.

    From the skin and subcutaneous fat: often - itching, skin rash; infrequently - excessive sweating; frequency unknown - angioedema.

    From the side of the musculoskeletal system and connective tissue: often - cramps in the calf muscles of the legs, musculoskeletal pain; infrequently - a pain in the back.

    From the side of the kidneys and urinary tract: often - a violation of kidney function.

    From the side of the reproductive system: infrequently - gynecomastia.

    General and local: infrequently - asthenia, malaise.

    Laboratory indicators: often - increasing the concentration of residual urea nitrogen inblood serum; infrequently, an increase in creatinine concentration, a decrease in epidermal growth factor receptor expression, an increase in serum glucose concentration.

    Infections: infrequently - a pyelonephritis.

    Overdose:

    The cases of an eplerenone overdose in humans are not described. The most likely manifestations of an overdose may be a decrease in blood pressure and hyperkalemia. Eplerenone not removed during hemodialysis. Determined that eplerenone actively binds to activated carbon. With a marked decrease in blood pressure, supportive treatment should be prescribed. In the case of hyperkalemia, standard therapy is indicated.

    Interaction:

    Pharmacodynamic interactions

    Potassium-sparing diuretics and potassium preparations

    Given the increased risk of hyperkalemia. eplerenone should not be prescribed to patients receiving potassium-sparing diuretics and potassium preparations (see the section "Contraindications"). Potassium-sparing diuretics can enhance the effects of antihypertensive drugs and other diuretics.

    Preparations containing lithium

    The interaction of eplerenone with lithium preparations has not been studied.However, patients who received lithium preparations in combination with diuretics and ACE inhibitors described cases of increased concentration and intoxication with lithium. If such a combination is necessary, it is advisable to monitor the concentration of lithium in the blood plasma (see section "Special instructions").

    Cyclosporin, tacrolimus

    Cyclosporine and tacrolimus may cause impaired renal function and increase the risk of hyperkalemia. You should avoid the simultaneous use of eplerenone and cyclosporine or tacrolimus. If the administration of cyclosporine or tacrolimus is required during eplerenone treatment, it is recommended that the serum potassium concentration and renal function be carefully monitored (see section "Special instructions").

    Nonsteroidal anti-inflammatory drugs (NSAIDs)

    Treatment with NSAIDs can lead to acute kidney failure by directly suppressing glomerular filtration, especially in patients at risk (elderly patients and / or patients with dehydration). With the joint application of these funds before and during treatment, it is necessary to provide an adequate water regime and monitor kidney function.

    Trimethoprim

    Simultaneous use of trimethoprim with eplerenone increases the risk of hyperkalemia. It is recommended to monitor the concentration of potassium in the blood serum and the function of the kidneys, especially in patients with renal insufficiency and in the elderly.

    ACE inhibitors and angiotensin II receptor antagonists

    When using eplerenone with ACE inhibitors or angiotensin II receptor antagonists, serum potassium levels should be carefully monitored. Such a combination may lead to an increased risk of hyperkalemia, especially in patients with impaired renal function, incl. in the elderly.

    Alfa1-adrenoblockers (prazozin, alfuzosin)

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

    Tricyclic antidepressants, antipsychotics, amifostine, baclofen

    With the simultaneous use of these funds with eplerenone, the antihypertensive effect may increase or the risk of developing orthostatic hypotension may increase.

    Glucocorticoids, tetracosactide

    The simultaneous use of these drugs with eplerenone can lead to a delay in sodium and liquid.

    Pharmacokinetic interactions

    Research in vitro evidence that eplerenone does not inhibit isoenzymes CYP1A2, CYP2C19, CYP2C9, CYP2D6 and CYP3A4. Eplerenone is not a substrate or inhibitor of the glycoprotein R.

    Digoxin: AUC digoxin with simultaneous use with eplerenone increases by 16% (90% CI: 4% -30%). Care must be taken if digoxin is used in doses close to the maximum therapeutic dose.

    Warfarin: clinically significant pharmacokinetic interaction with warfarin was not revealed. Care must be taken if warfarin is used in doses close to the maximum therapeutic dose.

    Substrates of the isoenzyme CYP3A4: in special studies of the signs of pharmacokinetic interaction of eplerenone with substrates of the isoenzyme CYP3A4, for example, midazolam and cisapride, was not revealed.

    Inhibitor inhibitors CYP3A4: potent inhibitors of isoenzyme CYP3A4 - with the use of eplerenone with agents inhibiting the isoenzyme CYP3A4, a significant pharmacokinetic interaction is possible.A potent inhibitor of the isoenzyme CYP3A4 (ketoconazole 200 mg twice daily) caused an increase in the AUC of eplerenone by 441%.

    Simultaneous use of eplerenone with potent inhibitors of isoenzyme CYP3A4, such as: ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin, telithromycin and nefazadone, is contraindicated (see section "Contraindications"); weak and moderate inhibitors of isoenzyme CYP3A4 - simultaneous use with erythromycin, saquinavir. amiodarone. diltiazem. verapamil and fluconazole was accompanied by a significant pharmacokinetic interaction (the degree of increase AUC ranged from 98% to 187%). With the simultaneous use of these funds with eplerenone, the dose of the latter should not exceed 25 mg (see section "Method of administration and dose").

    Inductors of isoenzyme CYP3A4

    Simultaneous administration of drugs containing St. John's wort (a powerful isoenzyme inducer CYP3A4) with eplerenone caused a decrease AUC the latter by 30%.

    When using more powerful isoenzyme inducers CYP3A4, such as rifampicin, perhaps a more pronounced decrease AUC eplerenone.

    Considering the possible decrease in the effectiveness of eplerenone, the simultaneous use of powerful isoenzyme inducers CYP3A4 (rifampicin, carbamazepine, phenytoin, phenobarbital, preparations containing St. John's wort perforated) is not recommended (see section "Special instructions").

    Antacids: the interaction of antacids with eplerenone in their simultaneous application is not expected.

    Special instructions:

    Hyperkalemia

    In the treatment of eplerenone, hyperkalemia may develop, which is due to its mechanism of action. At the beginning of treatment and when changing the dose of the drug in all patients should monitor the concentration of potassium in the blood serum. In the future, periodic monitoring of potassium concentration is recommended for patients with an increased risk of hyperkalemia, for example, the elderly, patients with renal insufficiency (see the "Application and dose" section) and diabetes mellitus. Given the increased risk of hyperkalemia, the appointment of potassium drugs after the initiation of eplerenone treatment is not recommended. Reducing the dose of eplerenone leads to a decrease in the concentration of potassium in the blood serum.

    Impaired renal function

    In patients with impaired renal function, including diabetic microalbuminuria, it is recommended that the concentration of potassium in the blood serum be monitored regularly.The risk of hyperkalemia increases with a decrease in kidney function. Although the number of patients with type 2 diabetes and microalbuminuria was limited in studies, nevertheless, the incidence of hyperkalemia increased. In this regard, in such patients, treatment should be conducted with caution. Eplerenone not removed during hemodialysis. For more information, see "Contraindications".

    Impaired liver function

    In patients with mild or moderate liver function disorder (5-6 and 7-9 points according to the Child-Pugh classification) no increase in serum potassium concentration> 5.5 mmol / l was detected. In such patients, the concentration of electrolytes should be monitored. In patients with impaired hepatic function eplerenone not studied, therefore its use is contraindicated (see the section "Contraindications").

    Inductors of isoenzyme CYP3A4

    Simultaneous use of eplerenone with powerful isoenzyme inducers CYP3A4 is not recommended (see section "Interaction with other drugs").

    Cyclosporine, tacrolimus, preparations containing lithium

    During the treatment with eplerenone, the prescription of these drugs should be avoided.section "Interaction with other drugs").

    Lactose

    Tablets contain lactose monohydrate, so they should not be prescribed to patients with rare hereditary intolerance to galactose, a deficiency of lactase, a syndrome of glucose-galactose malabsorption.

    Effect on the ability to drive transp. cf. and fur:

    Effects of eplerenone on the ability to drive a car or use machinery have not been studied. In recommended doses of 25 and 50 mg eplerenone Do not cause dizziness and fainting.

    Form release / dosage:

    Film-coated tablets, 25 mg and 50 mg.

    Packaging:

    For 10 tablets in a blister of PVC / PVDC / aluminum foil.

    3 blisters together with instructions for use in a cardboard box.

    Storage conditions:

    Store at a temperature not exceeding 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    2 years.

    Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-003959
    Date of registration:11.11.2016
    Expiration Date:11.11.2021
    The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel
    Manufacturer: & nbsp
    Representation: & nbspTeva Teva Israel
    Information update date: & nbsp12.12.2016
    Illustrated instructions
      Instructions
      Up