active substance: eplerenone;
1 tablet contains eplerenone 25 mg or 50 mg
auxiliary substances: lactose monohydrate, cellulose microcrystalline croscarmellose sodium; hypromellose (hydroxypropyl methylcellulose), sodium lauryl sulfate; talc magnesium stearate
shell: Opadry II Yellow 33G32799: hypromellose (hydroxypropyl methylcellulose) lactose monohydrate, polyethylene glycol; triacetin; titanium dioxide (E 171) iron oxide yellow (e 172).
Basic physical and chemical properties: tablets of round shape with concave surface, film-coated from light brownish yellow to bright yellow.
Potassium-sparing diuretics. Antagonists of aldosterone. Eplerenone. ATC code C03D A04.
Eplerenone has a relative selectivity in conjunction with recombinant human receptors in mineralocorticoids compared to its interaction with recombinant human receptors in glucocorticoids, progesterone and androgens. Eplerenon prevents binding receptors with aldosterone-an important hormone renin-angiotensin-involved in the regulation of blood pressure and is involved in the pathophysiological mechanisms of cardiovascular disease.
Eplerenone leads to a persistent increase in the level of renin in blood plasma and the level of aldosterone in serum, which is consistent with inhibition of the negative feedback path of the effect of aldosterone on renin secretion. At the same time, increased renin activity in blood plasma and aldosterone level in the blood does not lead to suppression of eplerenone.
In chronic heart failure (classes II-IV by NYHA classification), the addition of eplerenone to the standard treatment regimen resulted in an expected dose-dependent increase in aldosterone levels.
Studies have not revealed the sustained effect of eplerenone on heart rate, duration of QRs complex, or PR and QT intervals.
Children. The use of eplerenone in children with heart failure was studied. Studies of any (long-term) effect on the hormonal status of children were not carried out.
Absorption. The bioavailability of eplerenone is unknown. The maximum concentration of the drug in the blood plasma is achieved through 2:00. The maximum concentration in plasma (C max ) and area under the curve (AUC) changes proportionally with dose in the range 10-100 mg and less doseproportional in the application of doses more than 100mg. Equilibrium occurs within 2 days of starting treatment. Food does not affect the absorption of the drug.
Distribution. Eplerenone is associated with blood plasma proteins is 50%, and mainly with ? 1-kilimi glycoproteins. The volume of distribution of eplerenone in equilibrium is considered as such, equal to 50 ± 7 liters. Eplerenone is not subject to binding to erythrocytes.
Metabolism. Eplerenone metabolism is mainly carried out by the enzyme CYP3A4. No active eplerenone metabolites were found in human blood plasma.
Conclusion. Less than 5% of the dose of eplerenone is excreted in the urine and feces unchanged drug. After oral administration of a single dose of a radioactively labeled drug, approximately 32% of the dose was excreted from the body with feces and approximately 67% - with urine. Half-life of eplerenone is about 3-5 hours. The imaginary clearance of blood plasma is about 10 l/h.
Application to special groups of patients.
Age, gender and race. Studies of pharmacokinetics of eplerenone at a dose of 100 mg once a day was carried out in elderly people (over 65 years), in men and women, as well as in representatives of the Negroid race. Significant differences in pharmacokinetics of eplerenone in men and women have not been revealed. In elderly patients in the equilibrium state there was an increase in the levels of C max (22%) and AUC (45%) compared with younger patients (18-45 years). The blacks in the equilibrium state C max was lower by 19% and AUC below 26% (see "Method of application and dosage").
Children. It was found that the patient's body weight has a statistically significant effect on the volume of eplerenone distribution, but not on its output. It is assumed that the volume of eplerenone distribution and peak exposure in patients with higher body weight will be similar in adults with similar body weight. In patients with a body weight of 45 kg, the volume of distribution is lower (by almost 40%); it is assumed that the peak exposure is higher than that in adults.
Renal failure. Pharmacokinetics of eplerenone was assessed in patients with varying degrees of renal impairment and in patients on hemodialysis. In patients with severe renal insufficiency, the AUC and C max at steady state were increased by 38% and 24% respectively, compared with the control group. In patients who were on hemodialysis, these indicators were reduced by 26% and 3%, respectively, compared with the control group of patients. No correlation was found between eplerenone clearance from blood plasma and creatinine clearance. Eplerenone is not removed by hemodialysis (see Section "Peculiarities of use").
Liver failure. Pharmacokinetics of eplerenone at a dose of 400 mg was studied in patients with moderate liver lesions (class B according to child-Pugh classification) and compared with the results obtained for patients without liver dysfunction. C max and AUC eplerenone at steady state were increased by 3.6% and 42%, respectively (see "Method of application and dosage"). Since research applications eplerenone for the treatment of patients with severe liver dysfunction was not performed, the appointment eplerenone such patients is contraindicated (see "Contraindications").
Heart failure. Population analysis of the pharmacokinetics of eplerenone indicates that the clearance of eplerenone in patients with heart failure does not differ from the clearance of this drug in healthy elderly volunteers.
Addition to the standard treatment with beta-blockers to reduce risk of morbidity and mortality associated with cardiovascular disease in stable patients with left ventricular dysfunction (ejection fraction of left ventricle ? 40%) and clinical signs of heart failure after recent myocardial infarction.
Supplement to standard optimal therapy to reduce the risk of heart disease-related morbidity and mortality in adult class II heart failure (chronic) patients with NYHA classification and left ventricular dysfunction (left ventricular ejection fraction ? 30%) ( see Pharmacological section).
Hypersensitivity to eplerenone or to any of the excipients.
The level of potassium in the blood serum of>5 mmol/l at commencement of treatment.
Severe renal insufficiency (estimated glomerular filtration rate 2 ).
Severe hepatic insufficiency (class C according to child-Pugh classification).
Treatment potassium-sparing diuretic drugs, potassium-containing additives or potent CYP3A4 inhibitors (e.g. Itraconazole, ketoconazole, ritonavir, nelfinavir, clarithromycin, telithromycin and nefazodone) (see Section "Interaction with other medicinal products and other forms of interaction").
Simultaneous use of eplerenone in triple combination with ACE inhibitor and angiotensin receptor blockers.
Interaction with other medicinal products and other forms of interaction
Potassium-sparing diuretics and potassium-containing additives. Eplerenone should not be prescribed to patients who receive other potassium-sparing diuretics and potassium-containing supplements for an increased risk of hyperkalemia (see section "Contraindications").
Under the influence of potassium-sparing diuretics can also increase the effect of antihypertensive drugs and other diuretics.
ACE inhibitors, angiotensin receptor blockers. When using eplerenone in combination with ACE inhibitor and/or angiotensin receptor blocker, the risk of hyperkalemia may increase. It is recommended to carefully monitor the level of potassium in the blood serum and kidney function indicators, especially in patients at risk of renal impairment, for example in elderly patients. Eplerenone should not be used simultaneously in a triple combination with ACE inhibitor and blockers of receptors of angiotensin (see Sections "Contraindications" and "precautions").
Lithium. Studies of the interaction of eplerenone with lithium were not carried out. However, patients receiving lithium concurrently with ACE inhibitors and diuretics, have been described cases of toxic effects of lithium (see Section "Peculiarities of use"). Simultaneous use of eplerenone and lithium preparations should be avoided. If it is not possible to avoid the use of this combination, it is necessary to monitor the level of lithium in the blood plasma (see "Features of application").
Cyclosporine, tacrolimus. Cyclosporine and tacrolimus can lead to impaired renal function and increase the risk of hyperkalemia. Simultaneous use of eplerenone and cyclosporine or tacrolimus should be avoided. If necessary, the appointment of cyclosporine and tacrolimus during treatment with eplerenone is recommended to carefully monitor the level of potassium in the blood serum (see section "features of application").
Nonsteroidal anti-inflammatory drugs (NSAIDs). Due to the direct effect on the glomerular filtration treatment NSAIDs can cause acute renal failure, especially in patients belonging to the high-risk group (older age and/or dehydration). Patients receiving eplerenone and NSAIDs should ensure adequate water regime and control kidney function before starting treatment.
Trimethoprim. Simultaneous appointment of trimethoprim and eplerenone increases the risk of hyperkalemia. Should monitor the level of potassium in serum and indicators of renal function, especially in elderly patients and patients with impaired renal function.
? 1 blockers (e.g. prazosin, alfuzosin). When combining ? 1 blockers and eplerenone, it is possible to increase the antihypertensive action and/or the occurrence of orthostatic hypotension. In the case of simultaneous use of ? 1 blockers should monitor the clinical condition of patients by orthostatic hypotension.
Tricyclic antidepressants, neuroleptics, amifostine, baclofen. The simultaneous administration of these drugs and eplerenone can potentially increase the antihypertensive effect and increase the risk of orthostatic hypotension.
Glucocorticoids, tetracosactide. With the simultaneous appointment of these drugs and eplerenone, there is a possibility of weakening the hypotensive effect due to fluid and sodium retention.
In vitro studies indicate that eplerenone is not an inhibitor of CYP1A2 isoenzymes, CYP2C19, CYP2C9, CYP2D6 or CYP3A4. Eplerenone is not a substrate or inhibitor of P-glycoprotein.
Digoxin. The level of systemic exposure (AUC) digoxin while the use of eplerenone increases by 16% (90% CI: 4-30%). Should be used with caution digoxin in doses close to the upper limit of the therapeutic range.
Warfarin. Clinically relevant pharmacokinetic interactions with warfarin has not been described. Warfarin should be administered with caution in doses close to the upper limit of the therapeutic range.
Substrates of CYP3A4. The results of pharmacokinetic studies with samples-CYP3A4 substrates (ie, midazolam and cisapride) revealed no signs of pronounced pharmacokinetic interactions with concomitant use of these medicines and eplerenone.
Inhibitors of CYP3A4.
Strong inhibitors of CYP3A4. With the simultaneous use of eplerenone and drugs that inhibit the activity of the enzyme CYP3A4, it is possible to develop pronounced pharmacokinetic interactions. Under the influence of a powerful inhibitor CYP3A4 (ketoconazole 200 mg 2 times a day) AUC eplerenone increased by 441% (see section "Contraindications"). Contraindicated simultaneous application eplerenone and potent inhibitors of CYP3A4 (ketoconazole, Itraconazole, ritonavir, nelfinavir, clarithromycin, telithromycin and nefazodone) (see Section "Contraindications").
Weak and moderate inhibitors of CYP3A4. Concurrent use with erythromycin, saquinavir, amiodarone, diltiazem, verapamil and fluconazole led to a pronounced pharmacokinetic interactions with an increase in AUC levels at 98-187%. Accordingly, with the simultaneous appointment of eplerenone and mild or moderate inhibitors of CYP3A4 eplerenone dose should not exceed 25 mg (see section "dosage and Administration").
Inducers of CYP3A4. Simultaneous use of eplerenone and St. John's wort (CYP3A4 powerful inductor) led to a 30% decrease in AUC of eplerenone. The use of more potent inducers of CYP3A4 (such as rifampicin) may lead to a more pronounced decrease in AUC eplerenone. Due to the risk of reducing the effectiveness of eplerenone, it is not recommended to use powerful CYP3A4 inductors simultaneously with this drug (rifampicin, carbamazepine, phenytoin, phenobarbital, St. John's wort) (see "application Features").
Antacids. Based on the results of clinical pharmacokinetic studies, while the use of eplerenone and antacid drugs is not expected pronounced interactions.
Hyperkalemia. During treatment with eplerenone in accordance with its mechanism of action may develop hyperkalemia. All patients at the beginning of treatment and when changing the dose of the drug should monitor the level of potassium in the blood serum. 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 diabetes). After the start of treatment eplerenone is not recommended to use potassium supplements for increased risk of hyperkalemia. Reducing the dose of eplerenone leads to a decrease in the concentration of potassium in serum. During one study it was demonstrated that the additional administration of hydrochlorothiazide in the treatment of eplerenone compensated for the increase in the concentration of potassium in the blood serum.
When using eplerenone in combination with ACE inhibitor and/or angiotensin receptor blocker, the risk of hyperkalemia may increase.
Eplerenone should not be used simultaneously in a triple combination with ACE inhibitor and blockers of receptors of angiotensin (see Sections "Contraindications" and "Interaction with other medicinal products and other forms of interaction").
The impairment of renal function. In patients with impaired renal function (including diabetic microalbuminuria) should regularly monitor the level of potassium. The decline in renal function is accompanied by increased risk of hyperkalemia. In the group of patients with type 2 diabetes and microalbuminuria, an increased incidence of hyperkalemia was observed. Accordingly, treatment of such patients should be carried out with caution. Eplerenone is not removed by hemodialysis.
Impaired liver function. In patients with mild and moderate impaired liver function (classes A and b according to the classification of child-Pugh) increase the level of potassium in the blood serum of more than 5.5 mmol/l occurred. Such patients need control of electrolyte levels. The use of eplerenone for the treatment of patients with severe renal impairment has not been studied, so eplerenone is contraindicated in such patients (see Sections "dosage and Administration" and "Contraindications").
Inducers of CYP3A4. The simultaneous appointment eplerenone and strong CYP3A4 inducers is Not recommended (see "Interaction with other medicinal products and other forms of interaction").
Lithium, cyclosporine, tacrolimus should not be prescribed in the treatment of eplerenone (see section "Interaction with other drugs and other types of interactions").
In the composition of the drug includes lactose, therefore it should not be administered to patients with rare hereditary problems (galactose intolerance, congenital lactase deficiency or malabsorption syndrome of glucose and galactose).
Use during pregnancy or breast-feeding.
Pregnancy. There are no adequate data on the use of eplerenone for pregnant women. Data obtained in animal studies do not indicate a direct or indirect adverse effect on the course of pregnancy, embryo and fetus development, childbirth and postpartum development. To prescribe eplerenone to pregnant women with caution.
Lactation. Unknown, eplerenone passes into breast milk after oral administration. Since the potential for side effects in infants who are breastfed has not been investigated, a clinical decision should be made to discontinue breastfeeding or discontinue the drug, depending on the importance of treatment for women.
The ability to influence the reaction rate when driving motor transport or operating other mechanisms.
The study of the effect of eplerenone on the ability to drive vehicles or work with other mechanisms were not carried out. Eplerenone does not cause drowsiness or cognitive impairment, but when driving vehicles or operating machinery should take into account the possibility of dizziness during treatment with the medicine.
Method of application and doses
Eplerenone can be taken with food or regardless of the meal (see section "Pharmacokinetics").
The maximum daily dose of the drug is 50 mg per day.
Patients with heart failure after myocardial infarction. The recommended maintenance dose of eplerenone is 50 mg once a day. 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 advisable to reach this dose level in 4 weeks, taking into account the level of potassium in the blood serum (see the Table below). Treatment with eplerenone should usually begin 3-14 days after acute myocardial infarction.
Patients with class II heart failure (chronic) according to NYHA classification.
Treatment of patients with chronic heart failure class II classification NYHA should begin with a dose of 25 mg once a day and gradually increase to the target dose of 50 mg once a day. It is advisable to reach this dose level in 4 weeks, taking into account the level of potassium in the blood serum (see the Table below and the section "Features").
For patients whose potassium level in blood serum of greater than 5 mmol/l, you should not start treatment with eplerenone (see Section "Contraindications").
Serum potassium levels should be determined before treatment with eplerenone, during the first week of treatment and a month after treatment or dose adjustment. If necessary, periodically determine the level of potassium in the blood serum during treatment.
After starting treatment, the dose of the drug should be adjusted to take into account the concentration of potassium in the blood serum, as indicated in the table below.
Dose adjustment after starting treatment.
Concentration of potassium in serum (mmol/l)action dose correction
<5.0 increases 25 mg 1 time in 2 days to 25 mg 1 time per day.
With 25 mg 1 time per day to 50 mg 1 time per day
5,0-5,4 not change without izmeneniyu
The 5.5-5.9 snijenie 50 mg 1 time per day up to 25 mg 1 time per day.
With 25 mg 1 time per day to 25 mg 1 time in 2 days.
With 25 mg 1 every 2 days prior to temporary withdrawal
3 6.0 temporary cancellation-
After a temporary cancellation eplerenone due to the increase in the level of potassium in the 3 6 mmol/l recovery treatment perhaps in the dose of 25 mg 1 time in 2 days after lowering potassium concentration below 5 mmol/L.
Patients of advanced age.
For elderly patients, there is no need to correct the initial dose of the drug. Due to the age-related decrease in the intensity of renal function, the risk of hyperkalemia in elderly patients increases. The risk may further increase in the presence of concomitant disease, accompanied by an increase in the systemic exposure of the drug, in particular, a violation of the liver function of mild and moderate. It is recommended to carry out periodic monitoring of potassium level in blood serum (see section "Peculiarities of application").
The impairment of renal function.
Patients with mild renal impairment do not require correction of the initial dose. It is recommended to periodically monitor the level of potassium in the blood serum (see section "peculiarities of application") and adjust the dose of the drug in accordance with the table above.
Patients with impaired renal function of moderate severity (creatinine clearance 30-60 mg/ml) should start with a dose of 25 mg 1 every 2 days and adjust the dose depending on the concentration of potassium (see Table above). It is recommended to carry out periodic monitoring of potassium level in blood serum (see section "Peculiarities of application").
Experience of drug use in patients with creatinine clearance
Use of doses exceeding 25 mg per day for patients with creatinine clearance
Eplerenone is contraindicated in patients with severe renal impairment (creatinine clearance
Impaired liver function.
Patients with mild or moderate hepatic impairment do not require correction of the initial dose, but as a result of increasing the level of systemic exposure of eplerenone in this category of patients, and especially in elderly patients, frequent and regular monitoring of the concentration of potassium in the blood serum is recommended (see Section "application Features").
In the case of simultaneous application with weak or moderate CYP3A4 inhibitors (e.g. amiodarone, diltiazem and verapamil) can begin treatment with eplerenone starting dose 25 mg 1 times per day. The dose of the drug should not exceed 25 mg once a day (see section "Interaction with other drugs and other types of interactions").
Children. Safety and efficacy of eplerenone in children has not been established. Currently available information is given in the sections "Pharmacological" and "Pharmacokinetics".
Symptoms. No adverse reactions associated with eplerenone overdose were reported in humans. The most likely manifestations of drug overdose are arterial hypotension or hyperkalemia.
Treatment. Eplerenone is impossible to remove from the body by hemodialysis. Eplerenone effectively binds to activated carbon. In the case of hypotension should begin supportive treatment. In the development of hyperkalemia should begin treatment in accordance with the standards.
On the part of the blood and lymphatic system: eosinophilia.
From the endocrine system: hypothyroidism.
From the nervous system: dizziness, fainting, headaches, hypesthesia.
Cardiovascular system: myocardial infarction, left ventricular failure, atrial fibrillation, tachycardia, arterial hypotension, thrombosis of limb arteries, orthostatic hypotension.
From the respiratory system, chest and mediastinal organs: cough.
From the gastrointestinal tract: diarrhea, nausea, constipation, vomiting, bloating.
The skin and subcutaneous tissue: rash, pruritus, hyperhidrosis, angioedema.
From the musculoskeletal system and connective tissues muscle spasms, pain in the musculoskeletal system , back pain.
From the kidneys and urinary tract: impaired renal function (see Sections "Features of application" and "Interaction with other drugs and other types of interactions").
From the liver and biliary tract: cholecystitis.
From the reproductive system and mammary glands: gynecomastia.
Psychiatric disorders: insomnia.
From metabolism and digestion: hyperkalemia (see sections "Contraindications" and "Features of application"); hyponatremia, dehydration, hypercholesterinemia, hypertriglyceridemia.
General disorders: asthenia, malaise.
Infections and infestations: infections, pyelonephritis, pharyngitis.
Laboratory studies: urea increase, creatinine level increase, decrease in the number of receptors of epidermal growth factor, increase in blood glucose levels.
Store in the original packaging at a temperature not exceeding 25 ° C.
Keep out of reach of children.
There are 10 tablets in blister, 3 blisters in a pack.
Category home away from home
PJSC "Kyiv vitamin factory".
Manufacturer's location and address of the place of business
04073, Ukraine, g. . Kyiv, Kopylivska, 38.
Web-site: www.vitamin.com.ua Oh.
HOMVIO-PROSTAN ORAL DROPS 50ML
Homvio-Prostan drops for oral use-homeopathic medicine. The effect of the drug has a preventive and curative effect in diseases of the genitourinary tract. For easy use and accurate compliance with the dosing tool that comes in a vial-dropper.
With prolonged use, analgesic, anti-inflammatory, antispasmodic effect is observed. At the same time normalizes the muscle membrane of the bladder.
Uncontrolled self-treatment can worsen physical condition, so the drug and the therapy regimen are prescribed by the doctor when:
Small diseases of the genitourinary system.
The increase in size of the prostate gland (only male patients).
The chronic form of cystitis.
Chronic, acute urinary retention.
Instructions for use
When diagnosing the disease in a chronic form, Homvio-prostan is prescribed in a dosage of 10 drops to 3 times in 24 hours. The average daily norm can be increased to 15 drops on the lack of effectiveness of therapy.