Equamer® (Ekvamer)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Dosage form: & nbspcapsules
Composition:

Composition per 1 capsule:

Dosage of 5 mg + 10 mg + 10 mg

Active substances: Amlodipine besylate - 6.94 mg (equivalent to amlodipine 5 mg), lisinopril dihydrate - 10.88 mg (equivalent to lisinopril 10 mg), rosuvastatin calcium - 10.4 mg (equivalent to rosuvastatin 10 mg).

Excipients: cellulose microcrystalline, type 12 - 60.41 mg, microcrystalline cellulose, type 101 - 45.27 mg, lactose monohydrate - 48.1 mg, sodium carboxymethyl starch - 9.5 mg, magnesium hydroxide - 7.5 mg, magnesium stearate - 2 mg, Opadrai II yellow - 2 mg (contains: polyvinyl alcohol 40.0%, titanium dioxide 23.5%, macrogol-3350 20.2%, talc 14.8%, iron oxide yellow 1.5%), hard gelatin capsule 76 mg (contains: dye blue patented 0.00022%, dye azorubin 0.03684%, dye sunset yellow 0.0204%, titanium dioxide 3.7037%, gelatin up to 100%).

Dosage 5 mg + 10 mg + 20 mg

Active substances: Amlodipine besylate 6.94 mg (equivalent to amlodipine 5 mg), lisinopril dihydrate 10.88 mg (equivalent to lisinopril 10 mg), rosuvastatin calcium 20.8 mg (equivalent to rosuvastatin 20 mg).

ATExcipients: cellulose microcrystalline, type 12 - 86.41 mg, cellulose microcrystalline, type 101 - 45.27 mg, lactose monohydrate - 96.2 mg, sodium carboxymethyl starch - 17.5 mg, magnesium hydroxide - 15 mg,magnesium stearate - 3 mg Opadry II yellow - 4 mg (contains: polyvinyl alcohol 40.0%, 23.5% titanium dioxide, Macrogol 3350, 20.2%, 14.8% talc, iron oxide yellow dye 1.5 %), hard gelatin capsule - 76 mg (contains: dye azorubin 0.1600%, titanium dioxide, 8519%, gelatin up to 100%).

Dosage of 10 mg + 20 mg + 10 mg

Active substances: amlodipine besylate - 13.88 mg (amlodipine 10 mg equivalent) of lisinopril dihydrate - 21.76 mg (equivalent to 20 mg lizinoprilu), rosuvastatin calcium - 10.4 mg (equivalent to 10 mg of rosuvastatin).

Excipients: Microcrystalline cellulose, type 12 - 94.82 mg microcrystalline cellulose type 101 - 90.54 mg lactose monohydrate - 48,1mg, sodium carboxymethyl starch - 11 mg, magnesium hydroxide - 7.5 mg magnesium stearate - 3 mg Opadry II yellow - 2 mg (contains: polyvinyl alcohol 40.0%, 23.5% titanium dioxide, macrogol 3350, 20.2%, 14.8% talc, a colorant iron oxide yellow 1.5%), a hard gelatin capsule - 76 mg (contains: dye azorubin 0.0882%, indigocarmine 0.0284%, titanium dioxide 2.2056%, gelatin up to 100%).

Dosage of 10 mg + 20 mg + 20 mg

Active substances: Amlodipine besylate - 13.88 mg (equivalent to amlodipine 10 mg), lisinopril dihydrate - 21.76 mg (equivalent to 20 mg lizinoprilu), rosuvastatin calcium - 20.8 mg (equivalent to 20 mg of rosuvastatin).

Excipients: cellulose microcrystalline, type 12 - 120.82 mg, cellulose microcrystalline, type 101 - 90.54 mg, lactose monohydrate - 96.2 mg, sodium carboxymethyl starch - 19 mg, magnesium hydroxide - 15 mg, magnesium stearate - 4 mg, Opadrai II yellow - 4 mg (contains: polyvinyl alcohol 40.0%, titanium dioxide 23.5%, macrogol-3350 20.2%, talc 14.8%, iron oxide oxide yellow 1.5%), hard gelatin capsule 97 mg (contains: dye blue patented 0,02933%, dye azorubin 0.3067%, dye sunset yellow 0.02355%, titanium dioxide 3.7037%, gelatin up to 100%).

Description:

Dosage of 5 mg + 10 mg + 10 mg

Hard gelatin capsules of light pink color, size No. 1. Contents of capsules - 1 round, biconvex white tablet (contains lisinopril and amlodipine) and 1 round, biconvex tablet, film-coated, yellow (contains rosuvastatin).

Dosage 5 mg + 10 mg + 20 mg

Hard gelatin capsules in pink color, size No. 1. Contents of capsules - 1 round, biconvex white tablet (contains lisinopril and amlodipine) and 2 round, biconvex tablets, film-coated, yellow (contain rosuvastatin).

Dosage of 10 mg + 20 mg + 10 mg

Hard gelatin capsules of violet color, size No. 1. Contents of capsules - 2 round, biconvex white tablets (contain lisinopril and amlodipine) and 1 round, biconvex tablet, film-coated, yellow (contains rosuvastatin).

Dosage of 10 mg + 20 mg + 20 mg

Hard gelatin capsules of dark purple color, size No. 0. Contents of capsules - 2 round, biconvex tablets of white color (contain lisinopril and amlodipine) and 2 round, biconvex tablets, film-coated, yellow (contain rosuvastatin).

Pharmacotherapeutic group:The combined agent (blocker of "slow" calcium channels + angiotensin converting enzyme inhibitor + inhibitor of HMG-CoA reductase)
ATX: & nbsp
  • Rosuvastatin, amlodipine and lisinopril
    • Pharmacodynamics:

    Equamer® is a combined hypotensive and hypolipidemic drug. Part The preparation of Ecuymer® includes three active substances - amlodipine, lisinopril and rosuvastatin. The mechanism of action of the drug Ecwamer® is based on the pharmacological properties of the active substances.

    Amlodipine

    The dihydropyridine derivative blocking the "slow" calcium channels (BCCI) has antihypertensive and antianginal effects. It blocks "slow" calcium channels, reduces the transmembrane transition of calcium ions into the cell (mostly in the smooth muscle cells of the vessels, rather than in cardiomyocytes). Antianginal action is due to the expansion of coronary and peripheral arteries and arterioles:

    - with stenocardia reduces the severity of myocardial ischemia; expanding peripheral arterioles, reduces OPSS, reduces afterload on the heart, reduces the need for myocardium in oxygen;

    - Expanding coronary arteries and arterioles in unchanged and ischemic zones of the myocardium, increases the flow of oxygen into the myocardium (especially with vasospastic angina); prevents spasm of the coronary arteries (including caused by smoking).

    Have patients with stable angina, a single daily dose increases exercise tolerance, slows the development of angina attacks and (ischemic "segment depression ST, reduces the incidence of angina attacks and consumption of nitroglycerin and other nitrates.

    Has a long-term dose-dependent antihypertensive effect. Antihypertensive action is due to direct vasodilating effect on smooth muscle vessels. When hypertension single dose provides a clinically significant decrease in blood pressure (BP) over 24 hours (with the patient "lying" and "standing").

    Orthostatic hypotension with amlodipine is rare. Amlodipine does not cause a decrease in exercise tolerance, or a fraction of the left ventricular ejection. Reduces the degree of myocardial hypertrophy of the left ventricle. Does not affect the contractility and conductance of the myocardium, does not cause a reflex increase in the heart rate (HR), inhibits platelet aggregation, increases the glomerular filtration rate (GFR), and has a weak natriuretic effect. When diabetic nephropathy does not increase the severity of microalbuminuria. Does not have any adverse effect on metabolism and concentration of plasma lipids and can be used in the treatment of patients with bronchial asthma, diabetes and gout.Significant deprivation of blood pressure is observed after 6-10 h, the duration of the effect is 24 h.

    Have patients with diseases of the cardiovascular system (CCC) (including coronary atherosclerosis with one vessel and up to stenosis of 3 or more arteries, atherosclerosis of the zone arteries) who underwent myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA) or in patients with angina, the use of amlodipine prevents the development of thickening of the intima-media of the carotid arteries, reduces the mortality from myocardial infarction, stroke, PTCA, coronary artery bypass grafting; leads to a decrease in the number of hospitalizations for unstable angina and progression of chronic heart failure (CHF); reduces the frequency of interventions aimed at restoring coronary blood flow.

    Does not increase the risk of death or development of complications and deaths in patients with CHF (III-IV functional class by classification NYHA) on the background of therapy with digoxin, diuretics and angiotensin-converting enzyme (ACE) inhibitors. In patients with CHF (III-IV functional class by classification NYHA) non-ischemic etiology in the use of amlodipine, there is a possibility of pulmonary edema.

    Lisinopril

    Lizinopril - an ACE inhibitor.reduces the formation of angiotensin II from angiotensin I. Reducing the concentration of angiotensin II leads to a direct decrease in the release of aldosterone. Reduces the degradation of bradykinin and increases the synthesis of prostaglandins. Reduces the overall peripheral vascular resistance (OPSS), blood pressure, preload, pressure in the pulmonary capillaries, causes an increase in the minute volume of blood and increased tolerance of the myocardium to physical exertion in patients with CHF. Expands arteries more than veins. Some effects are explained by the effect on the tissue renin-angiotensin system. With prolonged use, myocardial hypertrophy and the walls of arteries of resistive type decrease.

    Improves the blood supply of the ischemic myocardium.

    ACE inhibitors prolong life expectancy in patients with CHF, slow the progression of left ventricular dysfunction in patients who underwent myocardial infarction without clinical manifestations of heart failure.

    The onset of action is 1 hour after ingestion. The maximum antihypertensive effect is determined after 6-7 hours and persists for 24 hours.With arterial hypertension, the effect is observed in the first days after the start of treatment, stable action develops after 1-2 months. With a sharp abolition of lisinopril ns marked increase in blood pressure. In addition to reducing blood pressure lisinopril reduces albuminuria. In patients with hyperglycemia contributes to the normalization of the function of the damaged glomerular endothelium. Lisinopril does not affect the concentration of glucose in the blood in patients with diabetes mellitus and does not increase the incidence of hypoglycemia.

    Rosuvastatin

    Rosuvastatin is a selective, competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A into mevalonate, the precursor of cholesterol. The main target of the action of rosuvastatin is liver, where the synthesis of cholesterol (Cholesterol) and catabolism of low density lipoproteins (LDL).

    Rosuvastatin increases the number of "liver" LDL receptors on the cell surface, increasing the uptake and catabolism of LDL, which in turn leads to inhibition of the synthesis of very low density lipoproteins (VLDL), thereby reducing the total number of LDL and VLDL.

    Rosuvastatin decreases the increased concentration of LDL cholesterol (LDL-C), total cholesterol and triglycerides (TG) and increases the concentration of cholesterol in high density lipoprotein (HDL-C) and also reduces the concentration with apolipoprotein B (apoB), neLPVP cholesterol, LDL-VLDL , TG-VLDL and increases the concentration of apolipoprotein A-I (ApoA-I) (See. Tables 1 and 2) decreases the ratio of LDL-C / HDL-C, total cholesterol / HDL-C, LDL-neLPVP / HDL-C ratio and apoB / ApoA-1.

    The therapeutic effect appears in the first week after the start of treatment with rosuvastatin, and after 2 weeks of treatment up to 90% of the maximum possible. The maximum therapeutic effect is usually achieved by the 4th week and is maintained with regular admission.

    Table 1. Dose-dependent effect in patients with primary hypercholesterolemia (type IIa and IIb according to Fredrickson classification) (the average adjusted percentage change compared to the original value).

    Dose

    amount

    patients

    HS-

    LDL

    General information

    HS

    HS-

    HDL

    TG

    xs-

    non-HDL

    Apo B

    Apo A-1

    Placebo

    13

    -7

    -5

    3

    -3

    -7

    -3

    0

    10 mg

    17

    -52

    -36

    14

    -10

    -48

    -42

    4

    20 mg

    17

    -55

    -40

    8

    -23

    -51

    -46

    5

    40 mg

    18

    -63

    -46

    10

    -28

    -60

    -54

    0

    Table 2. Dose-dependent effect in patients with hypertriglyceridemia (type IIb and IV according to Fredrickson's classification) (the average percentage change compared to the original value).

    Dose

    amount

    patients

    TG

    HS-

    LDL

    General information

    HS

    HS-

    HDL

    XFROM-

    non-HDL

    HS-

    VLDLP

    TG-

    VLDLP

    Placebo

    26

    1

    5

    1

    -3

    2

    2

    6

    10 mg

    23

    -37

    -45

    -40

    8

    -49

    -48

    -39

    20 mg

    27

    -37

    -31

    -34

    22

    -43

    -49

    -40

    40 mg

    25

    -43

    -43

    -40

    17

    -51

    -56

    -48














    Clinical efficiency

    Rosuvastatin is effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia, regardless of race, sex or age, including patients with diabetes mellitus and familial hypercholesterolemia.

    Have 80% of patients with hypercholesterolemia type IIa and IIb according to the Fredrickson classification (the average initial concentration of LDL-C is about 4.8 mmol / L) against the background of rosuvastatin 10 mg, the concentration of LDL-C is less than 3 mmol / l.

    In patients with homozygous familial hypercholesterolemia who took rosuvastatin in a dose of 20 mg and 40 mg, the average decrease in the concentration of LDL-C was 22%.

    In patients with hypertriglyceridemia with an initial TG concentration of 273 mg / dl to 817 mg / dL, rosuvastatin in doses from 5 mg to 40 mg once a day for 6 weeks, the concentration of TG in blood plasma decreased significantly (see Table 2).The additive effect is noted in combination with fenofibrate for the concentration of triglycerides and with nicotinic acid in relation to the concentration of cholesterolBP (see section "Special instructions").

    Pharmacokinetics:

    Amlodipine

    Suction

    After oral administration amlodipine slowly and almost completely absorbed from the gastrointestinal tract. The maximum concentration (CmOh) in the blood plasma is achieved 6-12 hours after admission. The average absolute bioavailability is 64-80%. Simultaneous food intake does not affect the absorption of amlodipine.

    Distribution and binding to blood plasma proteins

    The average volume of distribution is 21 l / kg body weight, indicating that most of the amlodipine is in the tissues, and the smaller is in the blood. Most of the amlodipine, which is in the blood (97.5%), binds to blood plasma proteins, equilibrium concentrations (Css) in blood plasma are achieved after 7-8 days of constant admission of amlodipine. Amlodipine penetrates through the blood-brain and placental barrier.

    Metabolism

    Amlodipine undergoes a slow but active metabolism in the liver in the absence of a significant effect of "primary transmission" through the liver. Metabolites do not have significant pharmacological activity.

    Excretion

    After a single admission of amlodipine, the elimination half-life (T1/2) varies from 35 to 50 hours, with repeated use is approximately 45 hours. About 60% of the ingested dose is excreted by the kidneys mainly in the form of metabolites, 10% - unchanged, and 20-25% - through the intestines with bile. Total clearance of amlodipine (leaves 0.116 ml / s / kg (7 ml / min / kg, 0.42 l / h / kg). Amlodipine not removed during hemodialysis.

    Pharmacokinetics the specific groups patients

    Patients with hepatic insufficiency

    The elongation T1/2 in patients with hepatic insufficiency suggests that with prolonged use, cumulation of amlodipine in the body will be higher (increases to 60 h).

    Patients with renal insufficiency

    Renal failure does not have a significant effect on the pharmacokinetics of amlodipine.

    Elderly patients (over 65 years of age)

    In elderly patients, excretion of amlodipine is slowed (T1/2 - 65 h) compared with young patients, but this difference has no clinical significance.

    Lisinopril

    Suction

    After oral administration, about 25% of lisinopril is absorbed from the gastrointestinal tract. Simultaneous food intake does not affect the absorption of lisinopril.Absorption is on average 30%, bioavailability is 29%.

    Distribution and binding to blood plasma proteins

    After ingestion CmOh lisinopril in blood plasma is achieved in 6-8 hours. Poorly binds to blood plasma proteins.

    Lizinopril weakly penetrates through the blood-brain and placental barrier.

    Metabolism

    Lizinopril is not biotransformed in the body.

    Excretion

    Lizinopril is excreted by the kidneys unchanged. T1/2 is 12 hours.

    Pharmacokinetics the separate patient groups

    Have patients with CHF absorption and clearance of lisinopril reduced, bioavailability is 16%.

    In patients with renal insufficiency (creatinine clearance less than 30 ml / min), the concentration of lisinopril is several times higher than the plasma concentration in healthy volunteers, with an increase in the time to reach CmOh in blood plasma and an increase in T1/2.

    In elderly patients, the concentration of lisinopril in the blood plasma and the area under the concentration-time curve are 2 times greater than in young patients.

    In patients with liver cirrhosis, the bioavailability of lisinopril is reduced by 30%, and the clearance by 50% compared to patients with normal liver function.

    In elderly patients, the concentration of lisinopril in the blood plasma is increased, on average, on 60%.

    Rosuvastatin

    Suction

    FROMmOh rosuvastatin in the blood plasma is reached approximately 5 hours after ingestion. Absolute bioavailability is approximately 20%.

    Distribution and binding to blood plasma proteins

    The volume distribution of rosuvastatin is approximately 134 liters. Approximately 90% of rosuvastatin binds to blood plasma proteins, mainly albumin.

    Metabolism

    The metabolism of rosuvastatin occurs predominantly in the liver, which is the main site for the synthesis of cholesterol and the metabolism of LDL-C. It is subject to limited metabolism (about 10%). Rosuvastatin is a non-core substrate for metabolism by isoenzymes of the cytochrome P450 system. The main isoenzyme involved in the metabolism of rosuvastatin is isoenzyme OYP2C9. Isozymes CYP2C19, CYP3A4 and CYP2D6 are less involved in metabolism.

    The main revealed metabolites of rosuvastatin are N-desmethyl and lactone metabolites. N-desmethyl is about 50% less active than rosuvastatin, lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity of inhibiting the circulating HMG-CoA reductase is provided by rosuvastatin, the rest - by its metabolites.

    Excretion

    About 90% of the dose is excreted unchanged through the intestine (including absorbed and unabsorbed rosuvastatin). The rest is excreted by the kidneys. Plasma half-life is approximately 19 hours. The half-life does not change with an increase in the dose of the drug. Average geometric the plasma clearance is approximately 50 l / h (coefficient of variation 21.7%). As in the case of other HMG-CoA reductase inhibitors, a membrane cholesterol transporter involved in the hepatic elimination of rosuvastatin plays an important role in the hepatic elimination of rosuvastatin.

    Linearity

    The systemic exposure of rosuvastatin increases in proportion to the dose. Pharmacokinetic parameters do not change with daily intake.

    Pharmacokinetics in selected patient groups

    Sex and age

    Sex and age do not have a clinically significant effect on the pharmacokinetics rosuvastatin.

    RAsian Affiliation

    Pharmacokinetic studies showed approximately a twofold increase in the median AUC (area under the concentration-time curve) and CmOh rosuvastatin in patients of the Mongoloid race (Japanese, Chinese, Filipinos,Vietnamese and Koreans) in comparison with patients of the European race; In patients of Indian nationality, studies showed an increase in the median AUC and CmOh in 1,3 times. Pharmacokinetic analysis did not reveal clinically significant differences in pharmacokinetics among representatives of Caucasoid and Negroid races.

    Patients with renal insufficiency

    In patients with mild to moderate renal failure, the plasma concentration of rosuvastatin or N-desmethyl does not change significantly. In patients with severe renal failure (CC less than 30 ml / min), the concentration of rosuvastatin in blood plasma is 3 times higher, and the concentration N-desmethyl is 9 times higher than that of healthy volunteers. The concentration of rosuvastatin in blood plasma in patients on hemodialysis was approximately 50% higher than in healthy volunteers.

    Patients with hepatic insufficiency

    Have patients with different stages of hepatic insufficiency no increase in T1/2 rosuvastatin in patients with a score of 7 or lower on the Child-Pugh scale. In two patients with scores of 8 and 9 on the Child-Pugh scale, an increase in T1/2, at least in 2 times.The experience with rosuvastatin in patients with a score above 9 but Child-Pugh scale is absent.

    Genetic polymorphism

    Inhibitors of HMG-CoA reductase, including rosuvastatin, are associated with transport proteins OATP1B1 (the polypeptide of the transport of organic anions, involved in the capture of statins by hepatocytes) and BCRP (efflux conveyor).

    In carriers of genotypes SLC01B1 (OATP1B1) C.521SS and ABCG2 (BCRP) C.421AA there was an increase in exposure (AUC) to rosuvastatin 1.6 and 2.4 times, respectively, compared with carriers of genotypes SLC01B1 P.521TT and ABCG2 C.421SS.

    Indications:

    Ekvamer® shown as replacement therapy in adult patients whose condition is already adequately controlled reception of amlodipine and rosuvastatin lisinopril at the same doses as in the preparation Ekvamer®, in the treatment of hypertension and related dyslipidaemia:

    - primary hypercholesterolemia (type IIbut according to Fredrickson's classification, with the exception of family heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb according to Fredrickson's classification), when diet and other non-pharmacological methods (for example, physical exercises, weight loss) are insufficient;

    - family homozygous hypercholesterolemia, when diet or other lipid-lowering therapy (eg, LDL-apheresis) is not effective enough;

    - Hypertriglyceridemia (type IV according to Fredrickson classification).

    Contraindications:

    - Hypersensitivity to amlodipine or other derivatives dihydropyridine.

    - Hypersensitivity to lisinopril or other ACE inhibitors.

    - Hypersensitivity to rosuvastatin.

    - Hypersensitivity to any of the excipients of the drug.

    - Angioedema in history, including the use of ACE inhibitors.

    - Hereditary or idiopathic angioedema.

    - Severe arterial hypotension (systolic blood pressure less than 90 mm Pg.).

    - Obstruction of the left ventricular outflow tract (including severe aortic stenosis).

    - Hemodynamically unstable heart failure after acute myocardial infarction.

    - The simultaneous use of the drug Ecwamer® with aliskiren-containing drugs in patients with diabetes mellitus or renal insufficiency (GFR less than 60 ml / min / 1.73 m2).

    - Liver disease in the active phase, including a persistent increase in the activity of transaminases in the blood serum, as well as any increase in the activity of transaminases (more than 3 times compared with the upper limit of the norm).

    - Severe renal dysfunction (KK less than 30 ml / min).

    - Myopathy.

    - Simultaneous reception of cyclosporine.

    - Predisposition to the development of myotoxic complications.

    - In women: pregnancy, the period of breastfeeding, the lack of adequate methods of contraception.

    - Children under 18 years of age (efficacy and safety not established).

    - Lactose intolerance, lactase deficiency or glucose-galactose malabsorption. Patients with hepatic insufficiency

    The experience with rosuvastatin in patients with a score above 9 on the Child-Pugh scale is not available (see the section "Pharmacokinetics").

    Carefully:

    Aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, arterial hypotension, cerebrovascular diseases (including cerebral circulatory insufficiency), ischemic heart disease, coronary insufficiency, CHF of non-ischemic etiology III-IV functional class by classification NYHA, acute myocardial infarction (and within 1 month after it), unstable angina, sinus node weakness syndrome (severe tachycardia or bradycardia), severe autoimmune systemic connective tissue diseases at t.ch.systemic lupus erythematosus, scleroderma), oppression of bone marrow hematopoiesis, diabetes mellitus, hyperkalemia, bilateral stenosis of the renal arteries, stenosis of the single kidney artery, condition after kidney transplantation, renal failure of mild and moderate severity (KK 30-80 ml / min), azotemia, primary aldosteronism, diet with restriction of table salt, conditions accompanied by a decrease in the volume of circulating blood (including vomiting, diarrhea), advanced age, liver failure of mild severity (5-6 points according to Child-Pugh) or moderate (7-9 points on a scale Child-Pugh), hypothyroidism, personal or family history of hereditary muscular diseases and previous history of muscle toxicity with the use of other HMG-CoA reductase inhibitors or fibrates, alcohol abuse, conditions in which increased plasma concentrations of rosuvastatin, race (Mongoloid race), simultaneous fibrate intake, history of liver disease, sepsis, extensive surgical intervention , trauma, severe metabolic, endocrine or water-electrolyte disorders or uncontrolled convulsive seizures.

    Pregnancy and lactation:

    Pregnancy

    The use of the drug Ecuamer is contraindicated during pregnancy.

    Adequate strictly controlled clinical studies to study the effects of the drug Equamer ® during pregnancy were not conducted.

    Admission of ACE inhibitors in the second and third trimesters of pregnancy can cause fetal and newborn death. It is possible to develop low salinity during pregnancy, as well as hypoplasia of the skull bones, deformation of the bones of the skull and face, hypoplasia of the lungs and impaired renal development in the newborn.

    Because cholesterol and other cholesterol biosynthesis products are important for fetal development, the potential risk of inhibiting HMG-CoA reductase is greater than the benefit of using rosuvastatin during pregnancy.

    Women of reproductive age should apply adequate methods of contraception. In case of pregnancy in the process of therapy, the drug should be immediately discontinued and, if necessary, alternative treatment should be prescribed.

    Do not start therapy with the drug Equamer ® during pregnancy. When planning pregnancy, you need to switch to alternative therapy with a proven safety profile during pregnancy.

    Breastfeeding period

    The use of the drug Ecuamer is contraindicated in the period of breastfeeding. It is not known whether the active substances are excreted into breast milk. It is known that they penetrate the milk of lactating rats. If you need to use the drug during lactation, breastfeeding should be discontinued.

    Fertility

    Adequate strictly controlled clinical studies to study the effect of the drug Ecuymer® on fertility have not been conducted.

    Dosing and Administration:

    Mode of application

    Equamer® can be taken regardless of the time you eat.

    Doses

    As a rule, the combination drug with fixed doses is not suitable for initial therapy.

    Equamer® is used as a substitute therapy in adult patients who already receive amlodipine, lisinopril and rosuvastatin in the same doses as in this preparation, and in which the titrated optimal maintenance doses are:

    Titrated optimal maintenance doses

    Preparation Equamer®

    amlodipine - 5 mg, lisinopril - 10 mg and rosuvastatin - 10 mg

    capsules with a dosage of 5 mg + 10 mg + 10 mg

    amlodipine - 5 mg, lisinopril - 10 mg and rosuvastatin - 20 mg

    capsules with a dosage of 5 mg + 10 mg + 20 mg

    amlodipine - 10 mg, lisinopril - 20 mg and rosuvastatin - 10 mg

    capsules with a dosage of 10 mg + 20 mg + 10 mg

    amlodipine - 10 mg, lisinopril - 20 mg and rosuvastatin - 20 mg

    capsules with a dosage of 10 mg + 20 mg + 20 mg

    The recommended dose of Ecuamer is 1 capsule per day. The maximum daily dose is 1 capsule.

    In the event that a dose adjustment is necessary, titration of the doses should be carried out by applying separately amlodipine, lisinopril and rosuvastatin.

    Special patient groups

    Patients with renal insufficiency

    During therapy with the drug Equamer®, kidney function, potassium and sodium in the blood plasma should be monitored. If the kidney function deteriorates, EcuMer® should be discarded. Such patients are recommended individual selection of doses separate active components. The use of the drug Ecwamer® in patients with severe renal failure is contraindicated in all doses (see section "Contraindications").

    Patients with hepatic insufficiency

    The drug Ecuymer® is contraindicated in patients with liver diseases in the active phase and patients with severe impairment of liver function (more than 9 on the Child-Pugh scale) (see "Contraindications").

    Children and adolescents (under 18 years of age)

    The safety and efficacy of EcuMer® in children and adolescents have not been established.

    Elderly patients (over 65 years of age)

    In older patients, the preparation of Ecuammer® should be used with caution.

    In clinical studies, no data were obtained on the change in the profile of the efficacy or safety of amlodipine, lisinopril or rosuvastatin, depending on age.

    Race

    When studying the pharmacokinetic parameters of rosuvastatin in patients belonging to different races, an increase in the systemic concentration of rosuvastatin in blood plasma among patients of the Mongoloid race was noted (see section "Special instructions"). This fact should be taken into account when prescribing the drug EcuMer® to this group of patients. When rosuvastatin is prescribed in a dose of 10 mg and 20 mg, the recommended initial dose of rosuvastatin for patients of the Mongoloid race should be 5 mg.

    Genetic polymorphism

    In carriers of genotypes SLC01B1 (OATP1B1) C.521SS and ABCG2 (BCRP) C.421AA increased exposure (AUC) to rosuvastatin in comparison with carriers of genotypes SLC01B1 P.521TT and ABCG2 C.421SS. For patient carriers of genotypes C.521SS and C.421AA the recommended maximum dose of rosuvastatin is 20 mg per day (see section "Pharmacokinetics").

    Concomitant therapy

    Rosuvastatin binds to various transport proteins (in particular, to OATP1B1 and BCR.P). When rosuvastatin is used together with medicinal products (such as ciclosporin, some human immunodeficiency virus (HIV) protease inhibitors, including a combination of ritonavir with atazanavir, lopinavir and / or tipranavir), which increase the concentration of rosuvastatin in blood plasma due to interaction with transport proteins, may increase the risk of myopathy (including rhabdomyolysis) (see " Special instructions "and" Interaction with other medicinal products "). In such cases, the possibility of appointing alternative therapy or temporary discontinuation of rosuvastatin. If the use of the above drugs is necessary, the relationship between the benefit and the risk of concomitant therapy with rosuvastatin should be evaluated and the possibility of depriving its dose should be considered (see section "Interaction with other drugs").

    Side effects:

    Undesirable adverse reactions are presented according to the system-organ classes according to the classification MedDRA and with the frequency of occurrence:

    Very often - 1/10 appointments (≥10%)

    Often - 1/100 of appointments (≥1%, but <10%)

    Not infrequently - 1/1000 appointments (≥0.1%, but <1%)

    Rarely - 1/10000 prescriptions (≥0.01%, at <0.1%)

    Very rarely - less than 1 / 10,000 appointments (<0.01%)

    The frequency is unknown - there is not enough data to estimate the frequency of development.

    Within each group, adverse reactions are distributed in order of decreasing importance.

    Separate treatment with amlodipine, lisinopril and rosuvastatin reported the following undesirable side reactions:

    Amlodipine

    Violations of the blood and lymphatic system

    Rarely: thrombocytopenic purpura, leukopenia, thrombocytopenia.

    Immune system disorders

    Infrequently: skin itching, rash (including erythematous and maculopapular rash, urticaria);

    Rarely: angioedema, erythema multiforme.

    Disorders from the metabolism and nutrition

    Rarely: hyperglycemia.

    Disorders of the psyche

    Infrequently: lability of mood, unusual dreams, increased excitability, depression, anxiety;

    Rarely: apathy, agitation, amnesia.

    Disturbances from the nervous system

    Often: headache, dizziness, fatigue, drowsiness;

    Infrequently: asthenia, malaise, hypoesthesia, paresthesia, peripheral neuropathy, tremor, muscle rigidity, insomnia, taste perversion;

    Rarely: convulsions;

    Rarely: Migraine, increased sweating, ataxia, parosmia.

    Disturbances on the part of the organ of sight

    Infrequently: diplopia, accommodation disorder, xerophthalmia, conjunctivitis, eye pain, visual impairment.

    Hearing disorders and labyrinthine disorders

    Infrequently: noise in ears.

    Heart Disease

    Often: increased heart rate;

    Rarely: development or aggravation of chronic heart failure, heart rhythm disturbances (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction, chest pain.

    Vascular disorders

    Often: peripheral edema (ankles and feet), "hot flashes";

    Infrequently: marked decrease in blood pressure;

    Rarely: fainting, vasculitis, orthostatic hypotension.

    Disturbances from the respiratory system, chest and mediastinal organs

    Infrequently: shortness of breath, rhinitis, nosebleeds;

    Rarely: cough.

    Disorders from the digestive system

    Often: nausea, abdominal pain;

    Infrequently: vomiting, constipation, diarrhea, flatulence, dyspepsia, anorexia, dryness of the oral mucosa, thirst;

    Rarely: gingival hyperplasia, increased appetite;

    Rarely: pancreatitis, gastritis.

    Disturbances from the liver and bile ducts

    Rarely: jaundice (usually cholestatic), hyperbilirubinemia, increased activity of "hepatic" transaminases, hepatitis.

    Disturbances from the skin and subcutaneous tissues

    Rarely: dermatitis;

    Rarely: alopecia, xeroderma, a "cold" sweat, a violation of skin pigmentation.

    Disturbances from musculoskeletal and connective tissue

    Infrequently: arthralgia, muscle cramps, myalgia, back pain, arthrosis;

    Rarely: myasthenia gravis.

    Disorders from the kidneys and urinary tract

    Infrequently: frequent urination, painful urination, nocturia;

    Rarely: dysuria, polyuria.

    Violations of the genitals and mammary gland

    Infrequently: erectile dysfunction, gynecomastia.

    General disorders and disorders at the site of administration

    Infrequently: pain of unspecified localization, increase / decrease in body weight.

    Lisinopril

    Violations of the blood and lymphatic system

    Rarely: reduction of hemoglobin and hematocrit;

    Rarely: oppression of bone marrow function, lymphadenopathy, leukopenia, neutropenia, agranulocytosis, thrombocytopenia, hemolytic anemia, anemia;

    Frequency unknown: erythropenia.

    Disorders from the immune system systems

    Infrequently: skin rash, itching;

    Rarely: angioedema, swelling of the face, limbs, lips, tongue, epiglottis and / or larynx;

    Rarely: intestinal angioedema, autoimmune diseases, an increase in the titer of antinuclear antibodies, an increase in the rate of erythrocyte sedimentation (ESR);

    Frequency unknown: eosinophilia, leukocytosis, fever (there are reports on the development volchanochnopodobnogo syndrome which may include fever, myalgia, arthralgia / arthritis, increased titer of antinuclear antibodies, increased erythrocyte sedimentation rate, eosinophilia, leukocytosis, may also develop a rash, photosensitivity reactions or other cutaneous manifestations) .

    Disorders from the endocrine system

    Frequency unknown: syndrome of inadequate secretion of antidiuretic hormone.

    Disorders from the metabolism and nutrition

    Rarely: hypoglycemia.

    Disorders of the psyche

    Often: sleep disturbance;

    Infrequently: mood lability;

    Rarely: confusion of consciousness;

    Frequency unknown: confusion, depression.

    Disturbances from the nervous system

    Often: dizziness, headache;

    Infrequently: paresthesia, drowsiness;

    Rarely: asthenic syndrome;

    Frequency unknown: syncope, convulsive twitching of the muscles of the face and limbs.

    Heart Disease

    Infrequently: chest pain, myocardial infarction (due to a pronounced decrease in blood pressure in groups of patients at increased risk);

    Rarely: tachycardia, bradycardia, aggravation of the course of chronic cardiac insufficiency, violation of atrioventricular conduction, heart palpitations.

    Vascular disorders

    Often: marked decrease in blood pressure;

    Infrequently: impaired cerebral circulation (due to a pronounced decrease in blood pressure the groups of patients at increased risk), Raynaud's syndrome;

    Rarely: orthostatic hypotension;

    Frequency unknown: vasculitis.

    Disturbances from the respiratory system, chest and mediastinal organs

    Often: "dry" cough, sinusitis, allergic alveolitis / eosinophilic pneumonia;

    Infrequently: rhinitis;

    Rarely: bronchospasm;

    Frequency unknown: dyspnea.

    Disorders from the digestive system

    Infrequently: dyspepsia, perversion of taste, abdominal pain;

    Rarely: dryness of the oral mucosa;

    Rarely: pancreatitis;

    Frequency unknown: anorexia.

    Disturbances from the liver and bile ducts

    Often: liver failure;

    Rarely: hepatocellular and cholestatic jaundice, hepatitis.

    Disturbances from the skin and subcutaneous tissue

    Infrequently: skin rash, itching;

    Rarely: urticaria, alopecia, psoriasis, photosensitivity;

    Rarely: increased sweating, pemphigus, Stevens-Johnson syndrome, toxic epidermal necrolysis, exudative erythema multiforme, pseudolymphoma of the skin.

    Disturbances from musculoskeletal and connective tissue

    Frequency unknown: myalgia, arthralgia / arthritis.

    Disorders from the kidneys and urinary tract

    Often: impaired renal function;

    Rarely: acute renal failure, uremia;

    Rarely: oliguria, anuria;

    Frequency unknown: proteinuria.

    Violations of the genitals and mammary gland

    Infrequently: decreased potency;

    Rarely: gynecomastia.

    Impact on the results of laboratory and instrumental studies

    Infrequently: hyperkalemia, hyponatremia, increased urea concentration and serum creatinine;

    Rarely: increased activity of "hepatic" enzymes, hyperbilirubinemia.

    With simultaneous use of ACE inhibitors and gold preparations for intravenous administration (sodium aurotomy malate) describes a symptom complex, which includes flushing of the facial skin, nausea, vomiting and a decrease in blood pressure.

    Rosuvastatin

    Side effects observed with the use of rosuvastatin, usually expressed slightly and pass independently. As with other inhibitors of HMG-CoA reductase, the incidence of side effects is mainly dose-dependent.

    Violations of the blood and lymphatic system

    Frequency unknown: thrombocytopenia.

    Immune system disorders

    Rarely: hypersensitivity reactions, including angioedema.

    Disorders from the endocrine system

    Often: diabetes mellitus type 2 (the frequency will depend on the presence or absence of risk factors (fasting glucose concentration> 5.6 mmol / L, BMI> 30 kg / m2, increased concentration of triglycerides, arterial hypertension in history)).

    Disorders of the psyche

    Frequency unknown: depression.

    Disturbances from the nervous system

    Often: headache, dizziness;

    Rarely: polyneuropathy, loss or loss of memory;

    Frequency unknown: peripheral neuropathy, sleep disorders (including insomnia and "nightmarish" dreams).

    Infringements from respiratory system, chest and mediastinal organs

    Frequency unknown: cough, shortness of breath.

    Disorders from the digestive system

    Often: constipation, nausea, abdominal pain;

    Rarely: pancreatitis;

    Frequency unknown: diarrhea.

    Disturbances from the liver and bile ducts

    Rarely: increased activity of "liver" transaminases;

    Rarely: jaundice, hepatitis.

    Disturbances from the skin and subcutaneous tissues

    Infrequently: skin itching, rash, hives;

    Frequency unknown: Stevens-Johnson syndrome.

    Disturbances from musculoskeletal and connective tissue

    Often: myalgia;

    Rarely: Myopathy (including myositis), rhabdomyolysis with or without acute renal failure;

    Rarely: arthralgia;

    Frequency unknown: immuno-mediated necrotizing myopathy, tendon diseases, in some cases complicated by rupture, temporary increase in activity of creatine phosphokinase (CK). In the case of increased activity of CK (more than 5 times compared with the upper limit of the norm) therapy should be suspended (see section "Special instructions").

    Infringements from kidney and urinary tract

    Rarely: hematuria;

    Frequency unknown: proteinuria.

    Violations of the genitals and mammary gland

    Frequency unknown: gynecomastia.

    General disorders and disorders at the site of administration

    Often: asthenia;

    Frequency unknown: peripheral edema.

    Impact on the results of laboratory and instrumental studies

    Frequency unknown: increased bilirubin concentration, blood glucose, increased glycosylated hemoglobin concentration, gamma-glutamyltranspeptidase activity, alkaline phosphatase, thyroid dysfunction.

    With the use of certain HMG-CoA reductase inhibitors, the following side effects have been reported: sexual dysfunction;

    in extremely rare cases, interstitial lung disease, especially with prolonged therapy (see section "Special instructions").

    If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, please tell your doctor.

    Overdose:

    There is no evidence of an overdose of Ecuymer®.

    Amlodipine

    Symptoms: marked decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (risk of development of severe and persistent arterial hypotension, including with the development of shock and death).

    Treatment: gastric lavage, the appointment of activated charcoal (especially in the first 2 hours after an overdose), maintaining the function of the cardiovascular system, elevated position of the lower limbs, control of the functions of the cardiovascular and respiratory systems, control of the volume of circulating blood (BCC) and diuresis. To restore the vascular tone - the use of vasoconstrictor (in the absencecontraindications to their use); to eliminate the effects of calcium channel blockade - intravenous calcium gluconate. Hemodialysis is ineffective.

    Lisinopril

    Symptoms: marked decrease in blood pressure, dry mouth, drowsiness, delay urination, constipation, anxiety, increased irritability, impaired renal function, water-electrolyte balance, tachycardia, bradycardia, collapse, hyperventilation of the lungs, dizziness.

    Treatment: symptomatic therapy, intravenous injection of 0.9% solution of sodium chloride and, if possible, the use of vasopressors, control of blood pressure, water-electrolyte balance. With stable bradycardia, an artificial pacemaker is possible. It is possible to use hemodialysis (see instructions for patients on hemodialysis in the section "Special instructions").

    Rosuvastatin

    With the simultaneous administration of several daily doses, the pharmacokinetic parameters of rosuvastatin do not change.

    There is no specific treatment for an overdose of rosuvastatin. In case of an overdose, it is recommended to carry out symptomatic treatment and measures aimed at maintaining the functions of vital organs and systems.It is necessary to monitor the liver function and the activity of CK. It is unlikely that hemodialysis will be effective.

    Interaction:

    Amlodipine

    Amlodipine can safely be used to treat arterial hypertension along with thiazide diuretics, alpha-adrenoblockers, beta-blockers, or ACE inhibitors. In patients with stable angina pectoris amlodipine can be combined with other antianginal agents, for example, with long-acting or short-acting nitrates, beta-blockers.

    Unlike other BCCI, the clinically significant interaction of amlodipine (III generation BCCI) was not detected when combined with non-steroidal anti-inflammatory drugs (NSAIDs), including indomethacin. It is possible to strengthen the anti-anginal and antihypertensive action of BCCC when combined with thiazide and loop diuretics, ACE inhibitors, beta-adrenoblockers and nitrates, as well as enhance their antihypertensive action when combined with alpha-blockers, antipsychotics.

    Although in the study of amlodipine, a negative inotropic effect was usually not observed, however,some BCCI may increase the severity of the negative inotropic effect of antiarrhythmic agents that cause lengthening of the interval QT (eg, amiodarone and quinidine).

    Amlodipine can also be safely administered concomitantly with antibiotics and hypoglycemic agents for oral administration.

    A single dose of 100 mg sildenafil in patients with essential hypertension does not affect the pharmacokinetics parameters of amlodipine.

    Repeated use of amlodipine in a dose of 10 mg and atorvastatin in a dose of 80 mg is not accompanied by significant changes in pharmacokinetics atorvastatin.

    Simvastatin: simultaneous repeated use of amlodipine in a dose of 10 mg and simvastatin at a dose of 80 mg leads to an increase in the exposure of simvastatin by 77%. In such cases, the dosage of simvastatin should be limited to 20 mg.

    Rozuvastatin: with simultaneous repeated use of amlodipine in a dose of 10 mg and rosuvastatin at a dose of 20 mg, an increase of about 28% AUC and by 31% CmOh rosuvastatin. The exact mechanism of interaction is unknown. It is expected that this effect will not be of clinical significance with the daily use of the drug Ecamer®, as it is only shown to those patients who are already receiving lisinopril, amlodipine and rosuvastatin in the same doses as in this combination.

    Ethanol (drinks containing alcohol): amlodipine with a single and repeated application in a dose of 10 mg does not affect the pharmacokinetics of ethanol.

    Antiviral drugs (ritonavir): increases plasma concentrations of BCCI, including amlodipine.

    Neuroleptics and isoflurane: increased antihypertensive effect of dihydropyridine derivatives.

    Calcium preparations can reduce the effect of BCCI.

    In the joint application of BCCI with lithium preparations (for amlodipine data are absent), the manifestation of their neurotoxicity may be enhanced (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

    Studies of simultaneous use of amlodipine and cyclosporine in healthy volunteers and all patient groups, except for patients after kidney transplantation, have been performed. Various studies of the interaction of amlodipine with cyclosporine in patients after kidney transplantation show that the use of this combination may not lead to any effect, or increase the minimum concentration of cyclosporin to varying degrees to 40%.These data should be taken into account and the concentration of cyclosporine in this group of patients should be monitored while cyclosporine and amlodipine are used simultaneously.

    Does not affect serum concentration digoxin and its renal clearance.

    Has no significant effect on the action warfarin (prothrombin time).

    Cimetidine does not affect the pharmacokinetics of amlodipine.

    In studies in vitro Amlodipine ns affects binding to plasma proteins digoxin, phenytoin, warfarin and indomethacin.

    Grapefruit juice: simultaneous single intake of 240 mg of grapefruit juice and 10 mg of amlodipine inside is not accompanied by a significant change in the pharmacokinetics of amlodipine. Nevertheless, it is not recommended to use grapefruit juice and amlodipine At the same time, as in the genetic polymorphism of the isoenzyme CYP3A4 it is possible to increase the bioavailability of amlodipine and, consequently, to increase the antihypertensive effect.

    Aluminum or magnesium-containing antacids: their single administration does not significantly affect the pharmacokinetics of amlodipine.

    Inhibitor inhibitors CYP3A4: with the simultaneous use of diltiazem 180 mg and amlodipine at a dose of 5 mg in elderly patients (from 69 to 87 years) with arterial hypertension, an increase in the system exposure of amlodipine by 57%. The simultaneous use of amlodipine and erythromycin in healthy volunteers (18 to 43 years old) does not lead to significant changes in exposure to amlodipine (an increase AUC on 22%). Despite the fact that the clinical significance of these effects is not completely clear, they can be more pronounced in elderly patients.

    Powerful inhibitors of isoenzyme CYP3A4 (eg, ketoconazole, itraconazole) can lead to an increase in the concentration of amlodipine in the blood plasma to a greater extent than diltiazem. It should be used with caution amlodipine and isoenzyme inhibitors CYP3A4.

    Inductors CYP3A4: data on the effect of inducers of isoenzyme CYP3A4 there is no pharmacokinetics of amlodipine. It is necessary to carefully monitor blood pressure while using amlodipine and isoenzyme inducers CYP3A4.

    Lisinopril

    When used simultaneously with potassium-sparing diuretics (spironolactone, eplerenone (spironolactone derivative), trpamterene, amiloride), potassium preparations, potassium-containing salt substitutes the risk of developing hyperkalemia increases, especially in patients with impaired renal function.

    When used simultaneously with diuretics - marked decrease in blood pressure. Concomitant use of lisinopril with beta-blockers, blockers "slow" calcium channel blockers, diuretics, tricyclic antidepressants / antipsychotics enhances antihypertensive action.

    When used simultaneously with nonsteroidal anti-inflammatory drugs (indomethacin and etc.), including acetylsalicylic acid> 3 g / day, estrogens, and adrenomimetics - decrease in antihypertensive action of lisinopril.

    Ppand simultaneous use with lithium preparations - slowing the excretion of lithium from the body.

    Simultaneous application with antacids and colestyramine slows down absorption in the gastrointestinal tract.

    Ethanol strengthens the action of lisinopril.

    Double blockade of the renin-angiotensin-aldosterone system (RAAS) by simultaneous application angiotensin II receptor antagonists (APA II), ACE inhibitors or aliskiren is associated with an increased incidence of arterial hypotension,hyperkalemia and renal dysfunction (including renal "sufficiency") compared with the use of one drug acting on RAAS.

    When used simultaneously with insulin and hypoglycemic agents for oral administration increases the risk of developing hypoglycemia.

    With simultaneous use of ACE inhibitors and preparations of gold for intravenous administration (sodium aurotomy malate) the symptom complex is described, including flushing of facial skin, nausea, vomiting and lowering blood pressure.

    The simultaneous use of lisinopril with acetylsalicylic acid as an antiplatelet agent, thrombolytic agents, beta-blockers and / or nitrates is not contraindicated.

    Simultaneous application with selective serotonin reuptake inhibitors can lead to severe hyponatraemia.

    Simultaneous application with allopurinol. procainamide, cytostatics may increase the risk of leukopenia.

    Rosuvastatin

    The effect of other drugs on rosuvastatin

    Inhibitors of transport proteins: rosuvastatin communicates with some transport proteins, in particular with OATP1B1 and BCRP. The concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in the concentration of rosuvastatin in the blood plasma and an increased risk of myopathy (see Table 3 and the sections on "Dosage and administration" and "Special instructions").

    Cyclosporine: with simultaneous application of rosuvastatin and cyclosporine AUC rosuvastatin was an average of 7 times higher than that seen in healthy volunteers (see section "Contraindications"). Does not affect the plasma concentration of cyclosporine. Rosuvastatin contraindicated in patients receiving ciclosporin (see section "Contraindications").

    Inhibitors of the human immunodeficiency virus protease: despite the fact that the exact mechanism of interaction is unknown, joint intake of HIV protease inhibitors can lead to a significant increase in exposure to rosuvastatin. A pharmacokinetic study on simultaneous use of 20 mg rosuvastatin and a combined preparation containing two HIV protease inhibitors (400 mg lopinavir / 100 mg ritonavir) in healthy volunteers resulted in approximately a two-fold and five-fold increase AUC(0-24) and Cmax respectively. Therefore, simultaneous administration of rosuvastatin and HIV protease inhibitors in the treatment of patients with human immunodeficiency virus is not recommended (see section "Specific guidance" and Table 3).

    Gemfibrozil and other lipid-lowering drugs: joint application rosuvastatin and gemfibrozil leads to an increase in 2 times the maximum concentration of rosuvastatin in blood plasma, as well as an increase AUC rosuvastatin (see section "Special instructions"). Based on the data on the specific interaction, it is expected pharmacokinetically significant interaction with fenofibrate, possibly pharmacodynamic interaction.

    Gemfibrozil, fenofibrate, other fibrates and a nicotinic acid in lipid-lowering doses (more than 1 g / day) increase the risk of myopathy with simultaneous application with HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy and when applied in monotherapy (see section "Special instructions" ).

    Ezetimibe: simultaneous application of rosuvastatin in a dose of 10 mg and ezetimibe at a dose of 10 mg was accompanied by an increase AUC rosuvastatin in patients with hypercholesterolemia (see Table 3).It can not be ruled out that the risk of side effects increases due to the pharmacodynamic interaction between rosuvastatin and ezetimibe.

    Antacids: simultaneous application of rosuvastatin and antacid suspensions, containing aluminum or magnesium hydroxide, leads to a decrease in the plasma concentration of rosuvastatin by approximately 50%. This effect is less pronounced if antacids are administered 2 hours after rosuvastatin administration. The clinical significance of this interaction has not been studied.

    Erythromycin: simultaneous application of rosuvastatin and erythromycin leads to a decrease AUC(().t) rosuvastatin by 20% and Cmax rosuvastatin by 30%. Such interaction can arise as a result of increased intestinal motility caused by the intake of erythromycin.

    Fusidic acid: Studies on the interaction of rosuvastatin and fusidic acid have not been conducted. As with other inhibitors of HMG-CoA reductase, post-marketing reports were received on cases of rhabdomyolysis with the combined use of rosuvastatin and fusidic acid. Patients should be closely monitored.If necessary, a temporary discontinuation of rosuvastatin is possible.

    Isozymes of cytochrome P450: research results in vivo and in vitro showed that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. Besides, rosuvastatin is a weak substrate for these enzymes. Therefore, interaction of rosuvastatin with other drugs at the metabolic level with the participation of cytochrome P450 isoenzymes is not expected. There was no clinically significant interaction between rosuvastatin and fluconazole (isozyme inhibitor CYP2C9 and CYP3A4) and ketoconazole (inhibitor of isoenzymes CYP2A6 and CYP3A4).

    Interaction with drugs, which requires correction of the dose of rosuvastatin (see Table 3)

    The dose of rosuvastatin should be adjusted when it is necessary to use it together with drugs that increase the exposure to rosuvastatin. If the exposure is expected to be 2 times or more, the initial dose of rosuvastatin should be 5 mg once a day. Also, the maximum daily dose of rosuvastatin should be adjusted,so that the expected exposure to rosuvastatin does not exceed that for a dose of 40 mg taken without the simultaneous administration of medications that interact with rosuvastatin. For example, the maximum daily dose of rosuvastatin with simultaneous use with gemfibrozil is 20 mg (1.9 times increase in exposure), with ritonavir / atazanavir 10 mg (increase in exposure 3.1 times).

    Table 3. Effect of concomitant therapy on exposure to rosuvastatin (AUC, data are listed in descending order) - results of published clinical trials

    Complementary therapy regimen

    Mode of taking rosuvastatin

    Change AUC rosuvastatin

    Cyclosporine 75-200 mg 2 times a day, 6 months.

    10 mg 1 time per day, 10 days

    An increase of 7.1 times

    Atazanavir 300 mg / ritonavir 100 mg 1 time per day, 8 days

    10 mg once

    Increase 3.1-fold

    Lopinavir 400 mg / ritonavir 100 mg 2 times per day, 17 days

    20 mg 1 time per day, 7 days

    An increase of 2.1 times

    Gemfibrozil 600 mg 2 times a day, 7 days

    80 mg once

    Increase 1.9 times

    Eltrombopag 75 mg 1 time per day, 10 days

    10 mg once

    Increase 1.6 times

    Darunavir 600 mg / ritonavir 100 mg 2 times per day, 7 days

    10 mg 1 time per day, 7 days

    Increase by 1.5 times

    Tipranavir 500 mg / ritonavir 200 mg 2 times at day, 11 days

    10 mg once

    Increase by 1.4 times

    Dronedarone 400 mg 2 times a day.

    No data

    Increase by 1.4 times

    Itraconazole 200 mg 1 time per day, 5 days

    10 mg or 80 mg once

    Increase by 1.4 times

    Ezetimibe 10 mg 1 time per day, 14 days

    10 mg once a day, 14 days

    Increase by 1.2 times

    Fosamprenavir 700 mg / ritonavir 100 mg 1 times a day, 8 days

    10 mg once

    Without changes

    Aleglitazar 0.3 mg, 7 days

    40 mg, 7 days

    Without changes

    Silymarin 140 mg 3 times a day, 5 days

    10 mg once

    Without changes

    Fenofibrate 67 mg 3 times a day, 7 days

    10 mg, 7 days

    Without changes

    Rifampin 450 mg once a day, 7 days

    20 mg once

    Without changes

    Ketoconazole 200 mg 2 times per day, 7 days

    80 mg once

    Without changes

    Fluconazole 200 mg 1 time per day, 11 days

    80 mg once

    Without changes

    Erythromycin 500 mg 4 times per day, 7 days

    80 mg once

    Decrease by 28%

    Baikalin 50 mg 3 times a day, 14 days

    20 mg once

    Decrease by 47%

    Clopidogrel 300 mg (loading dose), then 75 mg after 24 hours

    20 mg once

    2 times increase

    Symeprevir 152 mg 1 time per day, 7 days

    10 mg once

    An increase of 2.8 times

    Effect of rosuvastatin on other drugs

    Antagonists of vitamin K: as in the case of other HMG-CoA reductase inhibitors, initiation of rosuvastatin therapy or an increase in the dose of rosuvastatin in patients receiving both vitamin K antagonists (for example, warfarin or other coumarin anticoagulants) may lead to an increase in the international normalized relationship (INR). Abolition or reduction of the dose of rosuvastatin causes a decrease in MNO. In such cases, the INR should be monitored.

    Oral contraceptives / hormone replacement therapy: simultaneous use of rosuvastatin and oral contraceptives increases the AUC of ethinylestradiol and AUC norgestrel by 26% and 34%, respectively. Such an increase in plasma concentration should be taken into account when choosing a dose of oral contraceptives. Pharmacokinetic data on concurrent use Rozovastatin and hormone replacement therapy are absent. It is impossible to exclude a similar effect with the simultaneous use of rosuvastatin and hormone replacement therapy. However, this combination was widely used at the time of clinical trials and was well tolerated by patients.

    Other medicines: no clinically significant interaction between rosuvastatin and digoxin is expected.

    Special instructions:

    If you have been hospitalized, tell your doctor that you are taking Ecuymer ®.

    If you forget to take the capsule of the drug EcuMera, wait and take the next capsule at the usual time. Do not take a double dose to make up the missed dose.

    When using the preparation of Ecuymer®, recommendations for the use of the individual components of the preparation, detailed below, should be taken into account.

    Amlodipine

    It is necessary to maintain dental hygiene and supervision at the dentist (to prevent soreness, bleeding and gingival hyperplasia).

    Have elderly patients may increase T1 / 2 and decrease the clearance of amlodipine. Dosage adjustment is not required, but more careful monitoring is necessary behind patients of this category.

    The efficacy and safety of the use of amlodipine in hypertensive crisis is not established.

    Despite the absence of the "cancellation" syndrome in BCC, it is desirable to stop amlodipine treatment, gradually reducing the dose of the drug.

    Against the background of the use of amlodipine in patients with CHF of non-ischemic origin III and IV functional class by classification NYHA There was an increase in the incidence of pulmonary edema, despite the absence of signs of worsening heart failure.

    Lisinopril

    Symptomatic arterial hypotension

    Most often, a marked decrease in blood pressure occurs with a decrease in bcc caused by diuretic therapy, a reduction in table salt in the diet, dialysis, diarrhea and vomiting (see the sections "Interaction with other drugs" and "Side effect"). In patients with CHF, as with concomitant renal disease Mr.insufficiency, and in its absence, it is possible to develop symptomatic arterial hypotension. It was more often detected in patients with severe heart failure as a result of the use of large doses of diuretic, hyponatremia or impaired renal function. In such patients, therapy should be started under the strict supervision of a physician (with care to select a dose of lisinopril and diuretics). Similar rules should be adhered to when prescribing lisinopril to patients with coronary heart disease, cerebrovascular insufficiency, in which a sharp decrease in blood pressure can lead to myocardial infarction or stroke.

    In case of a marked decrease in blood pressure, the patient should be laid and, if necessary, compensated for fluid loss (intravenous infusion of 0.9% sodium chloride solution).

    Transient hypotensive reaction is not a contraindication for taking the next dose of lisinopril.

    With the use of lisinopril in some patients with CHF, but with normal or reduced blood pressure, there may be a decrease in blood pressure, which is usually not a reason for stopping therapy. In the event that arterial hypotension becomes symptomatic, a dose reduction or discontinuation of lisinopril therapy is necessary.

    In patients who have a risk of developing symptomatic arterial hypotension (on a diet with restriction of table salt or salt-free diet) with or without hyponatremia, as well as in patients who received high doses of diuretics. Before beginning treatment, it is necessary to compensate for the loss of fluid and salts.

    It is necessary to monitor the antihypertensive effect of the initial dose of lisinopril.

    Stenosis of the aortic and mitral valve / hypertrophic obstructive cardiomyopathy

    As with other ACE inhibitors, lisinopril should be administered with caution to patients with mitral valve stenosis and obstruction output a path of the left ventricle (aortic stenosis or hypertrophic obstructivecardiomyopathy).

    Acute myocardial infarction

    The use of standard therapy (thrombolytics, acetylsalicylic acid as an antiaggregant agent, beta-blockers).

    Lizinopril can be used together with intravenous nitroglycerin or with the use of transdermal nitroglycerin systems.

    Therapy with lisinopril should not be started in patients with acute myocardial infarction who have a risk of further serious hemodynamic deterioration after PThe use of vasodilators (patients with a systolic blood pressure of 100 mm Hg or lower, patients with cardiogenic shock). During the first 3 days after myocardial infarction, the dose of lisinopril should be reduced if systolic blood pressure is 120 mm Hg. Art. or lower. Maintenance doses of lisinopril should be reduced to 5 mg or temporarily to 2.5 mg if systolic blood pressure is 100 mm Hg. Art. or lower. If arterial hypotension persists (systolic blood pressure less than 90 mm Hg for more than 1 hour), do not continue to use lisinopril.

    Function violation kidneys

    In patients with CHF, a marked decrease in blood pressure after initiation of treatment with ACE inhibitors may lead to a further deterioration in kidney function. Cases of acute renal failure are noted.

    In patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney receiving ACE inhibitors, there was an increase in serum urea and serum creatinine, usually reversible after discontinuation of treatment and more common in patients with renal insufficiency.

    Lizinopril is not used for acute myocardial infarction in patients with severe renal dysfunction, which is established when the serum creatinine concentration exceeds 177 μmol / L and / or proteinuria exceeds 500 mg / day. If renal dysfunction develops during the treatment with lisinopril (a serum creatinine concentration greater than 265 μmol / L, or doubling in comparison with the pre-treatment value), the physician should assess the need for further use of lisinopril.

    Hypersensitivity / Angioedema

    The angioedema of the linden, limbs, lips, tongue, epiglottis and / or larynx that may occur at any time of therapy has rarely been seen in patients treated with an ACE inhibitor, including lisinopril. In this case, the therapy with lisinopril should be stopped as soon as possible and the patient should be monitored before the symptoms regress completely. In cases where the edema occurs only on the face and lips, this condition often passes without treatment, but it is possible to use antihistamines.

    Angioedema with edema of the larynx can be fatal. Swelling of the tongue, epiglottis or larynx can be the cause of airway obstruction, therefore it is necessary to immediately carry out appropriate therapy (0.3-0.5 ml of 1: 1000 epinephrine (epinephrine) solution subcutaneously) and / or take measures to ensure airway patency. It was noted that patients of the Negroid race, PACE inhibitors, angioneurotic edema developed more often than in patients of other races.

    In patients taking ACE inhibitors, there was rarely an intestinal angioedema. These patients complained of abdominal pain (with or without nausea and vomiting); in some cases, the previous angioedema was not observed, and the activity of C-1 esterase was within normal limits.Intestinal angioedema has been diagnosed by computed tomography of the gastrointestinal tract or ultrasound research, or surgical intervention; the symptoms disappeared after the withdrawal of the ACE inhibitor. When conducting differential diagnosis of abdominal pain in patients taking ACE inhibitors, development intestinal angioedema.

    Patients who have a history of angioedema, unrelated to previous treatment with ACE inhibitors, may have an increased risk of developing it during treatment with an AIIF inhibitor (see also "Contraindications"),

    Anaphylactic reactions for the procedure of desensitization

    In patients receiving ACE inhibitors during the course of desensitization (for example, the venom of Hymenoptera), in very rare cases development of life threatening anaphylactic reactions is possible. This can be avoided if the ACE inhibitor is temporarily discontinued before each desensitization procedure begins.

    Impaired liver function

    The use of ACE inhibitors can lead to the development of cholestatic jaundice with progression up to fulminant liver necrosis,therefore, it is necessary to stop taking lisinopril with an increase in the activity of "liver" transaminases and the appearance of symptoms of cholestasis.

    Patients on hemodialysis

    Anaphylactic reactions are also observed in patients on hemodialysis using high-flux membranes (for example, AN69®) and taking concomitantly ACE inhibitors. If you need hemodialysis, you need to use a different type of membrane or another antihypertensive drug.

    Cough

    When an ACE inhibitor was used, a "dry", prolonged cough, which disappeared after discontinuation of treatment with an ACE inhibitor, was noted. When a differential diagnosis of cough is necessary to consider and cough caused by the use of an ACE inhibitor.

    Surgery / General Anesthesia

    In patients whose condition requires extensive surgical intervention or general anesthesia with drugs that cause arterial hypotension, lisinopril can block the formation of angiotensin II with compensatory release of renin.

    The pronounced decrease in blood pressure, which is considered a consequence of this mechanism, can be eliminated by increasing the volume of circulating blood.

    Before surgery (including dental surgery), the surgeon / anesthesiologist should be informed of the use of an ACE inhibitor.

    Hyperkalemia

    There have been reports of hyperkalemia.

    Risk factors for the development of hyperkalemia include renal failure, diabetes mellitus, and simultaneous use of potassium-sparing diuretics (spironolactone, eplerenone (spironolactone derivative), triamterene and amiloride), potassium or salt substitutes containing potassium, especially in patients with impaired renal function.

    If it is necessary to simultaneously use lisinopril and these drugs, it is recommended to observe precautions and regularly monitor the potassium content in the blood serum.

    Patients with diabetes mellitus

    In patients with diabetes who take hypoglycemic drugs inside or receiving insulin, during the first month of treatment with an ACE inhibitor, careful monitoring of the glucose concentration in the blood plasma should be carried out.

    Double blockade of RAAS with antagonists of angiotensin-II (ARA II). inhibitors APF or aliskirenom

    It was proved that with the simultaneous use of antagonists of angiotensin-II ARA II), ACE inhibitors or aliskiren increases the risk of developing arterial hypotension, hyperkalemia, renal dysfunction (including acute renal failure). For this reason, combined use of ARA II, ACE inhibitors or aliskiren is not recommended.

    If the use of this therapy is necessary, it is recommended to observe a specialist, closely monitor the function of the kidneys, blood pressure and the content of electrolytes in the blood serum.

    ACE inhibitors, APA II should not be used in patients with diabetic nephropathy.

    Systemic connective tissue diseases

    In patients with severe autoimmune systemic diseases of connective tissue (including systemic lupus erythematosus, scleroderma) lisinopril should be used with caution.

    Elderly patients

    In elderly patients, the use of standard doses of lisinopril leads to a higher concentration of lisinopril in the blood, therefore special care is required in determining the dose, despite the fact that the differences in antihypertensive action of lisinopril in elderly and younger patientsrevealed.

    Rosuvastatin

    In patients receiving rosuvastatin, proteinuria can be detected. Changes in the amount of protein in the urine (from absence or trace amounts to ++ or more) are observed in less than 1% of patients receiving 10-20 mg of rosuvastatin and approximately 3% of patients receiving 40 mg of rosuvastatin. A slight change in the amount of protein in the urine was noted with a dose of 20 mg. In most cases, proteinuria decreases or disappears during therapy and does not indicate the onset or progression of an existing kidney disease.

    From the side of the musculoskeletal system

    When rosuvastatin was used in all dosages, and especially when taking doses exceeding 20 mg, the following undesirable side reactions were reported: myalgia, myopathy, in rare cases rhabdomyolysis.

    Determination of the activity of creatine phosphokinase

    Determination of CKK activity should not be performed after intensive physical exertion or in the presence of other possible causes of increased activity of CK, which may lead to incorrect interpretation of the results. In the event that the initial activity of CK is significantly increased (5 times higher than the upper limit of the norm), after 5-7 days, a second measurement should be made.Do not start therapy if a second test confirms the initial activity of CK (more than 5 times the upper limit of the norm).

    Before the start of therapy

    When prescribing rosuvastatin, as well as with the appointment of other inhibitors of HMG-CoA reductase, caution should be exercised in patients with existing risk factors for myopathy / rhabdomyolysis (see "With caution"). It is necessary to consider the risk / benefit ratio of therapy and to conduct clinical observation.

    During therapy

    The patient should be informed of the need to report immediately to the doctor about cases of sudden onset of muscle pain, muscle weakness, or spasms, especially in combination with malaise and fever. In such patients, the activity of CK should be determined. Therapy should be discontinued if the activity of CK is significantly increased (more than 5 times compared with the upper limit of the norm) or if the symptoms from the muscles are pronounced and cause daily discomfort (even if the activity of CK is 5 times lower compared to the upper limit of the norm ). If the symptoms disappear and CPK activity returns to normal,should consider the re-appointment of rosuvastatin or other inhibitors of HMG-CoA reductase in smaller doses with careful monitoring of the patient, routine monitoring of the activity of CKK in the absence of symptoms is not appropriate.

    There were no signs of increased effects on skeletal musculature with rosuvastatin and concomitant therapy. However, an increase in myositis and myopathy was reported in patients taking other HMG-CoA reductase inhibitors (statins) in combination with fibrin acid derivatives, including gemfibrozil, ciclosporin, nicotinic acid in lipid-lowering doses (more than 1 g / day), azole antifungal agents, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when combined with certain HMG-CoA reductase inhibitors. Thus, simultaneous use of rosuvastatin and gemfibrozil is not recommended. The risk / benefit ratio should be carefully weighed in the combined use of rosuvastatin and fibrates or nicotinic acid in lipid-lowering doses (more than 1 g / day). Contraindicated taking rosuvastatin 40 mg together with fibrates (see.section "Interaction with other drugs").

    After 2-4 weeks after starting treatment and / or increasing the dose of rosuvastatin, it is necessary to monitor the lipid metabolism (if necessary, adjust the dose of rosuvastatin).

    Control of liver function

    It is recommended to carry out the determination of liver function indices before the start of therapy and 3 months after the start of therapy. Taking rosuvastatin should stop or reduce its dose if the activity of "hepatic" transaminases in the serum is 3 times higher than the upper limit of the norm.

    In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, treatment of underlying diseases should be performed prior to treatment Rozuvastatin.

    Race

    AT During the study of pharmacokinetic parameters in patients belonging to the Mongoloid race, there was an increase in the systemic concentration of rosuvastatin by compared with the indices of patients of the European race (see the sections "Dosing and Administration" and "Pharmacokinetics").

    HIV protease inhibitors

    The combined use of rosuvastatin with HIV protease inhibitors is not recommended, see the "Interactions with Other Drugs" section).

    Interstitial lung disease

    Some inhibitors of HMG-CoA reductase (statins), especially for a long time, reported single cases of interstitial lung disease. Manifestations of the disease can be shortness of breath, unproductive cough and deterioration in overall health (weakness, weight loss and fever). If suspicion of interstitial lung disease should be stopped by statin therapy.

    Diabetes mellitus type 2

    In patients with a fasting glucose concentration of 5.6 to 6.9 mmol / L, rosuvastatin therapy was associated with an increased risk of developing type 2 diabetes mellitus.

    Excipients

    Lactose

    The drug EQUAMER® with a dosage of 5 mg + 10 mg + 10 mg and a dosage of 10 mg + 20 mg + 10 mg contains 48.10 mg of lactose monohydrate in each capsule. The drug Equamer® with a dosage of 5 mg + 10 mg + 20 mg and a dosage of 10 mg + 20 mg + 20 mg contains 96.20 mg lactose monohydrate in each capsule.

    Patients with such rare hereditary diseases as lactose intolerance, Lappease lactase deficiency or glucose-galactose malabsorption should not take the drug EcuMer.

    Dye azorubin

    The preparation Equamer® contains food coloring azorubin.

    Azorubin can cause the development of allergic reactions.

    Dye sunset sunset yellow

    The drug Equamer® dosage of 5 mg + 10 mg + 10 mg and 10 mg + 20 mg + 20 mg contains food coloring sunset yellow.

    Food coloring sunset yellow sunset can cause the development of allergic reactions.

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

    Data on the effect of the drug on the ability to drive vehicles and mechanisms are absent. In connection with the possible excessive decrease in blood pressure, dizziness, drowsiness and similar side effects, care should be taken when carrying out potentially hazardous activities requiring special attention and quick reactions (driving and other vehicles, working with moving mechanisms, dispatcher and operator work and etc.).

    Form release / dosage:

    Capsules, 5 mg + 10 mg + 10 mg, 5 mg + 10 mg + 20 mg, 10 mg + 20 mg + 10 mg, 10 mg + 20 mg + 20 mg.

    Packaging:

    5 capsules in a blister of PA / Al / PVC and aluminum foil. 6 blisters together with instructions for use are placed in a cardboard box. For 7 capsules in a blister of PA / Al / PVC and aluminum foil.For 4 blisters together with instructions for use are placed in a cardboard box. For 10 capsules in a blister of PA / Al / PVC and aluminum foil. For 3 blisters together with instructions for use are placed in a cardboard box.

    Storage conditions:

    In a place protected from moisture at a temperature of no higher than 30 ° C. Keep out of the reach of children.

    Shelf life:

    2 years.

    Do not use after the expiry date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-003094
    Date of registration:14.07.2015 / 29.01.2016
    Expiration Date:14.07.2020
    The owner of the registration certificate:GEDEON RICHTER, OJSC GEDEON RICHTER, OJSC Hungary
    Manufacturer: & nbsp
    Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary
    Information update date: & nbsp19.08.2016
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