Espiro (Espiro)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceEplerenoneEplerenone
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    • Dosage form: & nbspfilm coated tablets
    Composition:

    1 tablet (25 mg) contains:

    Active substance: eplerenone - 25,00 mg.

    Excipients: lactose monohydrate 38.67 mg, cellulose microcrystalline - 15.38 mg; hypromellose-15cP - 1.25 mg; sodium lauryl sulfate - 0.85 mg; croscarmellose sodium - 3.00 mg; magnesium stearate - 0.85 mg.

    Sheath:

    Opadry II 33G32578 (yellow) - 4.00 mg: hypromellose-6sP (E464) 1.60 mg; titanium dioxide (E171) - 0.91 mg; lactose monohydrate 0.84 mg; macrogol - 3350 - 0.32 mg; triacetin 0.24 mg; ferric iron oxide yellow (E172) - 0.09 mg.

    1 tablet (50 mg) contains:

    Active substance: eplerenone 50.00 mg.

    Excipients: lactose monohydrate - 77.34 mg; cellulose microcrystalline - 30.76 mg; hypromellose-15cP - 2.50 mg; sodium lauryl sulfate - 1.70 mg; croscarmellose sodium - 6.00 mg; magnesium stearate - 1.70 mg.

    Sheath:

    Opadrai II 33G32578 (yellow) - 8.00 mg: hypromellose-6sP (E464) - 3.20 mg; titanium dioxide (E171) - 1.82 mg; lactose monohydrate - 1.68 mg; macrogol-3350-0.64 mg; triacetin - 0.48 mg; ferric iron oxide yellow (E172) - 0.18 mg.

    Description:

    For tablets 25 mg: round, biconcave tablets, covered with a film coating of yellow color. Color of the tablet on the break: from white to almost white.

    For tablets 50 mg: round, biconcave tablets, covered with a film coat of yellow color, with a risk on one side. Color of the tablet on the break: from white to almost white.

    Pharmacotherapeutic group:diuretic potassium-sparing agent
    ATX: & nbsp

    C.03.D.A.04   Eplerenone

    Pharmacodynamics:

    Eplerenone has a high selectivity for mineralocorticoid receptors in humans in contrast to glucocorticoid, progesterone and androgen receptors and prevents the binding of mineralocorticoid with aldosterone, the key hormone of the renin-angiotensin-aldosterone system (RAAS), which is involved in the regulation of arterial pressure (AD) and cardiopulmonary pathogenesis -Vascular diseases.

    Eplerenone causes a persistent increase in renin activity in blood plasma and aldosterone in the serum. Subsequently, the secretion of renin is inhibited by aldosterone by the feedback mechanism. In this case, an increase in the activity of renin or the concentration of circulating aldosterone ns affects the effects of eplerenone. The significant effect of eplerenone on heart rate (heart rate), the duration of intervals QRS. PR or QT not found in healthy volunteers.

    Pharmacokinetics:

    Suction and distribution

    Absolute bioavailability of eplerenone is 69% after taking 100 mg of eplerenone orally in the form of tablets. Maximum concentration (Cmax) in blood plasma is achieved approximately 2 hours after ingestion. FROMmax and the area under the pharmacokinetic curve "concentration-time" (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

    The metabolism of eplerenone is carried out, mainly, under the action of the isoenzyme CYP3A4. Active metabolites of eplerenone in the 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 night. The half-life of eplerenone is about 3-5 hours, the clearance from the blood plasma is about 10 l / h.

    Special patient groups

    Age of sex 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 parameters of the pharmacokinetics of eplerenone in men and women did not differ significantly. In an equilibrium state in elderly patients Cmax and AUC were respectively 22% and 45% higher than in young patients (18-45 years).

    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 the patients of the control group, patients with severe renal insufficiency showed an increase in the equilibrium AUC and Cmax 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 ns is removed during hemodialysis.

    Liver failure: the pharmacokinetics of eplerenone at a dose of 400 mg were compared in patients with moderate impaired liver function (7-9 on the Child-Pugh scale) and healthy volunteers. Equilibrium Cmax 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 contraindicated.

    Heart failure: the pharmacokinetics of eplerenone at a dose of 50 mg were studied in patients with heart failure (II-IV functional class by classification NYHA). Equilibrium AUC and Cmax 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 less than 40%) and clinical signs of heart failure after a heart attack.

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

    Contraindications:

    Hypersensitivity to eplerenone or other components of the drug;

    - clinically significant hyperkalemia;

    - the content of potassium in the blood serum at the beginning of treatment is more than 5.0 mmol / l;

    - moderate or severe renal failure (creatinine clearance (CK) less than 30 ml / min in patients with chronic heart failure of the second class of functional class NYHA);

    - severe hepatic insufficiency (more than 9 on the Child-11oo scale);

    - simultaneous reception of potassium-sparing diuretics, potassium preparations or strong inhibitors of isoenzyme CYP3A4, for example, itraconazole, ketoconazole, ritonavir, nelfinavir, clarithromycia, telithromycin, and nsphazodone;

    - creatinine concentration in blood plasma> 2.0 mg / dl (or> 177 mmol / l) in men or> 1.8 mg / dl (or> 159 mmol / l) in women;

    - lactase insufficiency, lactose intolerance, glucose-galactose malabsorption;

    experience in the use of the drug in children under the age of 18 years, no, so its appointment to patients of this age group is not recommended.
    Carefully:

    - Diabetes mellitus type 2 and microalbuminuria;

    - simultaneous use of eplerenone and angiotensin-converting enzyme (AIP) inhibitors or angiotensin II receptor antagonists (ARAN); preparations containing lithium; cyclosporin or tacrolimus; digoxin and warfarin in doses close to the maximum therapeutic, strong isoenzyme inducers CYP3A4;

    - elderly age;

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

    Do not use a triple combination of an ACE inhibitor and ARAP with eplerenone.

    Pregnancy and lactation:

    There is no information on the use of the drug in pregnant women. Espiri should be given with caution and only when the expected benefit for the mother is significantly greater than the possible risk to the fetus / child.

    Information about the isolation 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 either to stop breastfeeding or to cancel the drug, depending on its importance for the mother.

    Dosing and Administration:

    Inside.

    Eating does not affect the absorption of Espiri.

    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 content in the serum (see Table 1). The recommended maintenance dose of Espiro is 50 mg once a day.

    Chronic heart failure and functional class by classification NYHA

    Treatment should begin with a dose of 25 mg once a day and increase it to 50 mg once a day through 4 pedules, taking into account the potassium content in the serum (see Table 1).

    Table №1. Selection of dose after treatment

    The content of potassium in the blood serum (mmol / l)

    Act

    Dose change

    <5,0

    dose increase

    from 25 mg every other day to 25 mg once daily from 25 mg once daily to 50 mg once daily

    5,0-5,4

    supportive

    dose

    the dose remains the same

    5,5-5,9

    dose reduction

    with 50 mg once a day to 25 mg once a day with 25 mg once a day to 25 mg every other day with 25 mg every other day - temporary cancellation of the drug

    >6,0

    cancellation

    not applicable

    The maximum daily dose is 50 mg.

    After the temporary discontinuation of Espiri in connection with an increase in serum potassium in the blood serum up to and above 6.0 mmol / l, Espiri therapy can be resumed at a dose of 25 mi- a day, when the potassium content in the serum is <5.0 mmol / l.

    General recommendations

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

    Elderly patients

    Correction of the initial dose in elderly patients is not required. In connection with the age-related decrease in renal function in elderly patients, the risk of developing hyperkalemia increases, especially in the presence of concomitant diseases that increase the concentration of zeplerenone in the blood serum, in particular when the liver function is disturbed from mild to moderate severity. It is recommended to periodically determine the potassium content in serum (see Table 1).

    Impaired renal function

    Correction of the initial dose in patients with mild renal impairment is not required. Degree of hyperkalemia increases with impaired renal function.

    It is recommended to periodically determine the potassium content in serum (see Table 1).

    Eplerenone is not removed during hemodialysis.In patients with severe renal failure (creatinine clearance <30 mL / min) is contraindicated drugs (see. The section "Contraindications").

    In patients with chronic cardiac insufficiency II functional class by classification NYIIA and violation of the function of the kidneys of moderate severity (CK 30-60 ml / min), it is necessary to start therapy with a dose of 25 mg every other day, followed by dose adjustment depending on the potassium content in the blood serum (see Table 1).

    The experience of using Espiro in patients with heart failure after myocardial infarction and KK <50 ml / min is not present. Caution should be used Espiro in these patients.

    In patients with SC <50 ml / min, the use of Espiri in a dose of 25 mg once a day was not investigated.

    Impaired liver function

    Correction of the initial 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 content be monitored regularly, especially in elderly patients.

    The use of Espiri in patients with severe impairment of liver function is contraindicated (see section "Contraindications").

    Concomitant therapy

    With the simultaneous use of drugs that have a weak or moderately expressed inhibitory effect on the isoenzyme CYP3A4. for example, erythromycin, saquipavir, amiodarone, diltiazem, veranamyl and fluconazole, treatment with Espiri 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 medicinal products ").

    Side effects:

    The following undesirable effects are given in accordance with the following grades of their incidence in accordance with the classification of the World Health Organization: very often (> 10%); often (> 1%, <10%); infrequently (> 0.1%, <1%); rarely (> 0.01%, <0.1%); very rarely (<0.01%, including individual messages); frequency is unknown (but it is not possible to establish the frequency of occurrence).

    Infectious diseases: infrequently - a pyelonephritis, a gynecomastia.

    Violations from the blood and lymphatic system: infrequently - eosinophilia. Disorders from the endocrine system: infrequently - hypothyroidism.

    Disorders from the metabolism and nutrition: often - hyperkalemia, hypercholesterolemia, hypertriglyceridemia, dehydration; infrequently - hyponatremia.

    Disorders of the psyche: infrequently - insomnia.

    Impaired nervous system: often - dizziness, fainting; infrequently - a headache, hypoesthesia.

    Heart Disease: often - myocardial infarction; infrequently - atrial fibrillation, left ventricular failure, tachycardia.

    Vascular disorders: often - marked reduction in blood pressure (BP): infrequently - orthostatic hypotension, thrombosis of the arteries of the lower extremities.

    Disorders from the respiratory system, the thoracic and mediastinal organs: often - cough; infrequently pharyngitis.

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

    Disorders from the liver and bile ducts: infrequently - cholecystitis.

    Disturbances from the skin and subcutaneous tissues: often - itchy skin; infrequently - increased sweating, skin rash; frequency unknown - angioedema.

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

    Disorders from the kidneys and urinary tract: often - a violation of kidney function.

    General disorders and disorders at the site of administration: infrequently - asthenia, malaise. Laboratory and instrumental data: infrequently, an increase in the concentration of residual urea nitrogen, creatinine. a decrease in the expression of the epidermal growth factor receptor, an increase in serum glucose concentration.

    Overdose:

    The cases of an eulerenone overdose in humans are not described. The most likely manifestations of an overdose may be a marked decrease in blood pressure and gynecology.

    Treatment: with the development of a marked decrease in blood pressure, it is necessary to appoint

    supporting treatment. In the case of hyperkalemia, standard therapy is indicated.

    Eplerenone is not removed during hemodialysis. It is established that enlerenone is actively bound to activated carbon.

    Interaction:

    Pharmacodynamic interactions

    Potassium-sparing diuretics and potassium preparations: taking into account the increased risk of hyperkalemia, eplerenone Do not prescribe to patients receiving potassium-sparing diuretics and potassium preparations.Potassium-sparing diuretics can enhance the effects of antihypertensive drugs and other diuretics.

    Preparations containing lithium: The interaction of eulerenone with lithium preparations has not been studied. However, in patients who received lithium preparations in combination with diuretics and inhibitors of AMP. cases of increased concentration and intoxication with lithium are described. If such a combination is necessary, it is advisable to monitor the lithium content in the blood plasma.

    Cyclosporine, takrotshus: ciclosporin and tacrolimus can cause disruption of the function of the nights and increase the risk of hyperkalemia. It should avoid the simultaneous use of eplerenoid and cyclosporine or tacrolimus. If ceposporin or tacrolimus is required during treatment with eplerenioi, it is recommended that the serum potassium content and renal function be monitored regularly. Non-steroidal anti-inflammatory drugs (NSAIDs): treatment III1VP can lead to acute renal failure due to direct inhibition of 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 application of trimethoprim with eplerenoi increases the risk of hypercaliemia. It is recommended to monitor the content of the stone in the blood serum and the function of the kidneys, especially in patients with renal insufficiency and in elderly patients.

    Inhibitors of AIF and angiotensin II receptor antagonists: When using eplerenone with ACE inhibitors or angiotensin II receptor antagonists, serum potassium should be monitored regularly. Such a combination can lead to an increased risk of hypercaliemia, especially in patients with impaired renal function, incl. in elderly patients.

    Do not use a triple combination inhibitor APF and APA II with enlerion.

    Alpha-adrenoblockers (prazozn, alfuzozn): with the simultaneous use of alpha 1-addressblockers with eplerenone, the antiplatelet effect may increase and / or the risk of orthostatic hypotension may increase, and therefore it is recommended to monitor BP when the body position changes.

    Tricyclic antidepressants, neuroleptics, amnfostine, baclofen: at the simultaneous use of these drugs with eplerenone may increase the antihypertensive effect or increase the risk of developing orthostatic hypotension.

    Glucocorticosteroids, tetracosactide: the simultaneous use of these drugs with eplerenone can lead to a delay in sodium and liquid.

    Pharmacokinetic interactions

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

    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 isoenzyme substrates CYP3A4, for example, midazolam and cisapride, was not identified.

    Inhibitors of isofermite CYP3A4

    Strong inhibitors of isoenzyme CYP3A4: when using an eplerzion with isozyme inhibitory agents CYP3A4, possibly significant pharmacokinetic interaction. Strong inhibitor CYP3A4 (ketoconazole 200 mg twice daily) caused an increase AIJC eplersiona by 441%. Simultaneous use of eplerenone with strong inhibitors of isoenzyme CYP3A4, such as ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin, telithrominine and nefazadone, is contraindicated (see section "Contraindications").

    Weak and moderate isoenzyme inhibitors 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 strong inducer CYP3A4) with eplerenone caused a decrease AUC the latter by 30%. When using stronger inductors CYP3A4, such as rifampies, perhaps a more pronounced decrease AUC eplersion. Considering the possible decrease in the effectiveness of eplerenone, the simultaneous use of strong inducers CYP3A4 (rifampicin, carbamazepine, phenytoin, phenobarbital, preparations containing St. John's wort perforated) is not recommended.

    LNTACIDES: based on a pharmacokinetic clinical study

    significant interaction of antacids with eplerenone in their simultaneous application is not expected.

    Special instructions:

    Hyperkalemia

    When treating with Espiri, 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 potassium content in the blood serum. In the future, periodic monitoring of potassium content is recommended for patients with an increased risk of hyperkalemia, for example, elderly patients, patients with renal insufficiency and diabetes mellitus. Given the increased risk of developing ginkerkalemni, the appointment of potassium drugs after the start of treatment with Espiro is not recommended.Reducing the dose of Espiri leads to a decrease in potassium in the blood serum. In one study, the addition of hydrochlorothiazide to eplerenone prevented an increase in potassium in the serum.

    Impaired renal function

    In patients with impaired renal function, including diabetic microalbuminuria, it is recommended to regularly monitor the potassium content in the serum. 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 the studies, nevertheless, an increase in the incidence of hyperkalemia was noted in this small sample. In this regard, in such patients, treatment should be conducted with caution. Eplerenone not removed during hemodialysis. The use of Espiro is contraindicated in cases of severe renal failure (see "Contraindications").

    Impaired liver function

    In patients with mild or moderate impairment of liver function (5-6 and 7-9 on the Child-Pugh scale), there was no increase in serum potassium in the serum more than 5.5 mmol / l. In such patients, the electrolyte content should be monitored.In patients with severe impairment of liver function eplerenone not studied, therefore its use is contraindicated (see the section "Contraindications").

    Inductors of isoenzyme CYPSA4

    Simultaneous use of Espiro with strong isoenzyme inducers CYP3A4 not recommended (see section "Interaction with other medicinal products").

    Cyclosporine, tacropimus, preparations containing lithium

    During the treatment with Espiro, these agents should be avoided (see section "Interaction with other medicinal products").

    Lactose

    Tablets contain lactose, so they should not be prescribed to patients with rare hereditary diseases, such as lactose intolerance, lactase deficiency and malabsorption glucose-galactose syndrome.

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

    The influence of Espiro's drug on the ability to drive vehicles or use sophisticated technology has not been studied. However, given the possibility of the drug to cause dizziness and fainting, caution should be exercised when driving vehicles or using complex equipment while taking Espiro.

    Form release / dosage:

    Film-coated tablets, 25 mg and 50 mg.

    Packaging:

    10 tablets per blister of PVC film and aluminum foil.

    3 or 9 blisters together with instructions for use are swept into a pack of cardboard.

    Storage conditions:

    At a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use the drug after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-002910
    Date of registration:13.03.2015
    The owner of the registration certificate:Pharmaceutical factory "POLFARMA" JSCPharmaceutical factory "POLFARMA" JSC Poland
    Manufacturer: & nbsp
    Representation: & nbspAKRIKHIN OJSC AKRIKHIN OJSC Russia
    Information update date: & nbsp16.11.2015
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