Equamer caps 10mg + 20mg +10mg #30

Equamer instruction

You can buy Equamer here

Composition

on 1 capsule:
Dosage 5 mg + 10 mg + 10 mg
active ingredient: 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: microcrystalline cellulose, type 12 - 60.41 mg, microcrystalline cellulose, type 101 - 45.27 mg, lactose monohydrate - 48.1 mg, carboxymethyl starch sodium - 9.5 mg, magnesium hydroxide - 7.5 mg, magnesium stearate - 2 mg, Opadry II yellow - 2 mg (contains: polyvinyl alcohol 40.0%, titanium dioxide 23.5%, macrogol-3350 20.2%, talc 14.8%, iron dye yellow oxide 1.5% ), hard gelatin capsule - 76 mg- (contains: patented blue 0.00022% dye, azorubine dye 0.03684%, sunset sunflower yellow yellow 0.0204%, titanium dioxide 3.7037%, gelatin up to 100%).
Dosage 5 mg + 10 mg + 20 mg
active ingredient: 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).
excipients: microcrystalline cellulose, type 12–86.41 mg, microcrystalline cellulose, type 101–45.27 mg, lactose monohydrate — 96.2 mg, carboxymethyl starch sodium — 17.5 mg, magnesium hydroxide — 15 mg, magnesium tetarate 3 mg, Opadry II yellow - 4 mg (contains: polyvinyl alcohol 40.0%, titanium dioxide 23.5%, macrogol-3350 20.2%, talcum 14.8%, iron dye yellow oxide 1.5%), hard gelatin capsule - 76 mg (contains: azorubine dye 0.1600%, titanium dioxide 1.8519%, gelatin up to 100%).
Dosage 10 mg + 20 mg + 10 mg
active ingredient: amlodipine besylate - 13.88 mg (equivalent to amlodipine 0 mg), lisinopril dihydrate - 21.76 mg (equivalent to lisinopril 20 mg), rosuvastatin calcium - 10.4 mg (equivalent to rosuvastatin 10 mg).
excipients: microcrystalline cellulose, type 12 - 94.82 mg, microcrystalline cellulose, type 101 - 90.54 mg, lactose monohydrate - 48.1 mg, carboxymethyl starch sodium - 11 mg, magnesium hydroxide - 7.5 mg, magnesium stearate - 3 mg, Opadray II yellow - 2 mg (contains: polyvinyl alcohol 40.0%, titanium dioxide 23.5%, macrogol-3350 20.2%, talcum 14.8%, iron dye yellow oxide 1.5%), solid gelatin capsule - 76 mg (contains: dye azorubine 0.0882%, indigo carmine 0.0284%, titanium dioxide 2.2056%, gelatin up to 100%).
Dosage 10 mg + 20 mg + 20 mg
active ingredient: amlodipine besylate - 13.88 mg (equivalent to amlodipine 10 mg), lisinopril dihydrate - 21.76 mg (equivalent to lisinopril 20 mg), rosuvastatin calcium - 20.8 mg (equivalent to rosuvastatin 20 mg).
excipients: microcrystalline cellulose, type 12 - 120.82 mg, microcrystalline cellulose, type 101 - 90.54 mg, lactose monohydrate - 96.2 mg, sodium carboxymethyl starch - 19 mg, magnesium hydroxide - 15 mg, magnesium stearate - 4 mg , Opadray II yellow - 4 mg (contains: polyvinyl alcohol 40.0%, titanium dioxide 23.5%, macrogol-3350 20.2%, talcum 14.8%, iron dye yellow oxide 1.5%), hard gelatin capsule - 97 mg (contains: patented blue dye 0,02933%, dye azorubine 0.3067%, sunset dye yellow sunset 0.02355%, titanium dioxide 3.7037%, gelatin up to 100%).

Description

Dosage 5 mg + 10 mg + 10 mg
Light pink hard gelatin capsules, size No. 1. The contents of the capsules are 1 round, white biconvex tablet (containing lisinopril and amlodipine) and 1 round, film-coated biconvex tablet, yellow color contains rosuvastatin).
Dosage 5 mg + 10 mg + 20 mg
Pink hard gelatin capsules, size No. 1. The contents of the capsules are 1 round, white biconvex tablet (containing lisinopril and amlodipine) and 2 round, film-coated biconvex tablets, yellow (contain rosuvastatin).
Dosage 10 mg + 20 mg + 10 mg
The hard gelatin capsules are purple in color, size No. 1. The contents of the capsules are 2 round, white biconvex tablets (contain lisinopril and amlodipine) and 1 round, film-coated biconvex tablet, yellow (contains rosuvastatin).
Dosage 10 mg + 20 mg + 20 mg
Dark-violet hard gelatin capsules, size No. 0. The contents of the capsules are 2 round, biconvex tablets of white color (contain lisinopril and amlodipine) and 2 round, biconvex tablets coated with a film, yellow color (contain rosuvastatin).
Pharmacotherapeutic group:
combined agent (blocker of “slow” calcium channels + angiotensin-converting enzyme inhibitor + inhibitor of HMG-Co-A reductase).
ATH code:
C10BX07

Pharmacodynamics

Equamer is a combined antihypertensive and lipid-lowering drug. Equamer contains three active ingredients - amlodipine, lisinopril and rosuvastatin. The mechanism of action of the drug Equamer is based on the pharmacological properties of active substances.

Amlodipine

The dihydropyridine derivative is a blocker of “slow” calcium channels (BMCC), it has antihypertensive effect and antianginal effect. It blocks "slow" calcium channels, reduces the transmembrane transition of calcium ions into the cell (to a greater extent in vascular smooth muscle cells than in cardiomyocytes).

Antianginal action due to the expansion of coronary and peripheral arteries and arterioles:

    with angina reduces the severity of myocardial ischemia; expanding peripheral arterioles, reduces round focal disease, reduces afterload on the heart, reduces myocardial oxygen demand;
    expanding the coronary arteries and arterioles in the unchanged and ischemic areas 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).

In patients with stable angina, a single daily dose increases exercise tolerance, slows the development of strokes and ischemic ST depression, reduces the frequency of strokes and the consumption of nitroglycerin and other nitrates.
It has a long dose-dependent antihypertensive effect. The antihypertensive effect is due to the direct vasodilating effect on vascular smooth muscle. In case of arterial hypertension, a single dose provides a clinically significant decrease in blood pressure (BP) for 24 hours (in the patient's position "lying" and "standing").
Orthostatic hypotension is quite rare with amlodipine.
Amlodipine does not cause a decrease in exercise tolerance, left ventricular ejection fraction. Reduces the degree of hypertrophy of the left ventricular myocardium.
It has no effect on myocardial contractility and conductivity, does not cause a reflex increase in heart rate (HR), inhibits platelet aggregation, increases glomerular filtration rate (GFR), and has a weak natriuretic effect. In diabetic nephropathy does not increase the severity of microalbuminuria. It does not have any adverse effect on metabolism and plasma lipid concentration and can be used in the treatment of patients with bronchial asthma, diabetes mellitus and gout. A significant decrease in blood pressure is observed after 6-10 hours, the duration of the effect is 24 hours.
In patients with diseases of the cardiovascular system (CVS) (including coronary atherosclerosis with lesion of one vessel and up to stenosis of 3 or more arteries, atherosclerosis of the carotid arteries) who have had a myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA) or in patients with angina pectoris , the use of amlodipine prevents the development of carotid intimal media thickening, reduces mortality from myocardial infarction, stroke, PTCA, coronary artery bypass surgery;
leads to a decrease in the number of hospitalizations for unstable angina pectoris and progress to chronic heart failure (CHF); reduces the frequency of interventions aimed at restoring coronary blood flow.
It does not increase the risk of death or the development of complications and deaths in patients with XCN (III-IV functional class but the NYIIA classification) during therapy with digoxin, diuretics, and angiotensin-converting enzyme (ACE) inhibitors.
In patients with CHF (III-IV functional class according to the NYHA classification) of non-ischemic etiology when using amlodipine, there is a likelihood of pulmonary edema.

Lisinopril

Lisinopril - an ACE inhibitor, reduces the formation of angiotensin II from angiotensin I.
A decrease in the concentration of angiotensin II leads to a direct decrease in the release of aldosterone. Reduces the degradation of bradykinin and increases prostaglandin synthesis. Reduces total peripheral vascular resistance (OPS), blood pressure. preload, pressure in the pulmonary capillaries, causes an increase in the minute volume of blood and an increase in myocardial tolerance to physical exertion in patients with CHF. Expands arteries to a greater extent than veins. Some effects are attributed to effects on the tissue renin-angiotensin system. With prolonged use, hypertrophy of the myocardium and the walls of resistive arteries is reduced.
Improves blood supply to ischemic myocardium.
ACE inhibitors prolong life expectancy in patients with CHF, slow down the progression of left ventricular dysfunction in patients who have had a myocardial infarction without clinical manifestations of heart failure.
Onset of action - 1 hour after ingestion. The maximum antihypertensive effect is determined after 6-7 hours and lasts for 24 hours. With arterial hypertension, the effect is observed in the first days after the start of treatment, a stable effect develops after 1-2 months. With a sharp cancellation of lisinopril, no marked increase in blood pressure was observed. In addition to lowering blood pressure, lisinopril reduces albuminuria. In patients with hyperglycemia, it helps normalize the function of the damaged glomerular endothelium. Lisinopril does not affect the concentration of glucose in the blood of patients with diabetes mellitus and does not lead to an increase in hypoglycemia.

Rosuvastatin

Rosuvastatin is a selective, competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor of cholesterol. The main target of the action of rosuvastatin is where the synthesis of cholesterol (cholesterol) and the catabolism of low-density lipoproteins (LDL) take place.
Rosuvastatin increases the number of “hepatic” 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 lowers elevated concentrations of LDL cholesterol (LDL-C), total cholesterol and triglycerides (TG) and increases the concentration of high-density lipoprotein cholesterol (HDL-C), and also reduces the concentration of apolipoprotein B (ApoV), LDL-C, non-LPVP, C-lymphocytes, and cholesterol-HDL-C; TG-VLDL and increases the concentration of apolipoprotein AI (ApoA-I) (see Tables 1 and 2), decreases the C-LDL / C-HDL-C ratio, total C-C / C-C-HDL, C-C-HDL-C / C-C-HDL and A / A ratio. ApoA-1.
The therapeutic effect appears during the first week after the start of rosuvastatin therapy and after 2 weeks of treatment reaches 90% of the maximum possible.
The maximum therapeutic effect is usually achieved by the 4th week and is maintained with regular intake.

Clinical efficacy

Rosuvastatin is effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia, regardless of race, gender, or age, including patients with diabetes and familial hypercholesterolemia.
In 80% of patients with hypercholesterolemia type IIa and IIb according to Fredrickson's classification (the average initial concentration of LDL-C LDL is about 4.8 mmol / l) while receiving rosuvastatin in a dose of 10 mg, the concentration of LD-C LDL reaches less than 3 mmol / l.
In patients with homozygous familial hypercholesterolemia who took rosuvastatin at 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, who received rosuvastatin in doses of 5 mg and 40 mg once a day for 6 weeks, the plasma TG concentration significantly decreased (see table 2).
The additive effect is observed in combination with fenofibrate in relation to the concentration of triglycerides and with nicotinic acid in relation to the concentration of HDL-C (see "Special instructions").

Pharmacokinetics

Amlodipine

Suction
After oral administration, amlodipine is slowly and almost completely absorbed from the gastrointestinal tract. The maximum concentration (Cmax) in the blood plasma is reached 6-12 hours after administration. The average absolute bioavailability is 64-80%. A simultaneous meal does not affect the absorption of amlodipine.
Distribution and binding to plasma proteins
The average volume of distribution is 21 l / kg body weight, which indicates that most of the amlodipine is in the tissues, and a smaller part is in the blood. Most of the amlodipine in the blood (97.5%) binds to plasma proteins.
Equilibrium plasma concentrations (Css) are achieved after 7–8 days of continuous administration of amlodipine. Amlodipine penetrates 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 passage" through the liver. Metabolites do not have significant pharmacological activity.
Removal
After a single dose of amlodipine, the half-life (T½) 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. The total clearance of amlodipine is 0.116 ml / s / kg (7 ml / min / kg, 0.42 l / h / kg). Amlodinin is not removed by hemodialysis.

Pharmacokinetics in selected groups of patients

Patients with liver failure

Elongation of T½ in patients with hepatic insufficiency suggests that with prolonged use cumulation of amlodipine in the body will be higher (increases to 60 hours).

Patients with renal failure

Renal failure has no significant effect on the pharmacokinetics of amlodipine.

Elderly patients (over 65)

In older patients, the elimination of amlodipine is slow (T½ - 65 hours) compared with young patients, but this difference has no clinical significance.

Lisinopril

Suction
After ingestion, about 25% of lisinopril is absorbed from the gastrointestinal tract. Simultaneous food intake does not affect the absorption of lisinopril. Absorption averages 30%, bioavailability -29%.
Distribution and binding to plasma proteins
After ingestion C max of lisinopril in blood plasma is achieved after 6-8 hours. Poorly bound to plasma proteins.
Lisinopril weakly penetrates the hematoencephalic and placental barrier.
Metabolism
Lisinopril is not biotransformed in the body.
Removal
Lisinopril is excreted by the kidneys unchanged. T½ is 12 hours.

Pharmacokinetics in selected groups of patients

In patients with CHF, the absorption and clearance of lisinopril is reduced, the bioavailability is 16%.
In patients with renal insufficiency (creatinine clearance (CC) less than 30 ml / min), lisinopril concentration is several times higher than plasma levels in healthy volunteers, with an increase in plasma Cmax and an increase in T½.
Elderly patients have lisinopril concentration in the blood plasma and the area under the concentration-time curve is 2 times greater than in young patients.
In patients with cirrhosis of the liver, the bioavailability of lisinopril is reduced by 30%, and the clearance is 50% compared with patients with normal liver function.
In elderly patients, lisinopril concentration in plasma is increased, on average, by 60%.

Rosuvastatin

Suction
Cmax of rosuvastatin in blood plasma is reached approximately 5 hours after ingestion. Absolute bioavailability is approximately 20%.
Distribution and binding to plasma proteins
The volume of distribution of rosuvastatin is approximately 134 liters. Approximately 90% of rosuvastatin binds to plasma proteins, mainly albumin.
Metabolism
Rosuvastatin metabolism occurs predominantly in the liver, which is the main site of cholesterol synthesis and LDL-C metabolism. Subject to limited metabolism (about 10%). Rosuvastatin is a non-core substrate for metabolism by cytochrome P450 isoenzymes. The main isoenzyme involved in rosuvastatin metabolism is OYP2C9. CYP2C19, CYP3A4 and CYP2D6 isoenzymes are less involved in metabolism.
The main identified 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 on inhibition of circulating HMG-CoA reductase is provided by rosuvastatin, the rest is provided by its metabolites.
Removal
About 90% of the dose is excreted unchanged through the intestines (including absorbed and unabsorbed rosuvastatin). The rest is excreted by the kidneys. The plasma half-life is approximately 19 hours. The half-life does not change with increasing dose of Equamer. The geometric mean plasma clearance is approximately 50 l / h (coefficient of variation 21.7%). As in the case of other HMG-CoA reductase inhibitors, membrane cholesterol transporter, which plays an important role in hepatic elimination of rosuvastatin, is involved in the process of hepatic capture 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 groups of patients

Gender and Age

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

Race

Pharmacokinetic studies showed an approximately twofold increase in the AUC median (area under the concentration-time curve) and Rosuvastatin Cm in Mongoloid patients (Japanese, Chinese, Filipinos, Vietnamese and Koreans) compared with Caucasians; In Indian patients, studies showed an increase in the median AUC and C max by 1.3 times. Pharmacokinetic analysis revealed no clinically significant differences in pharmacokinetics among the Caucasoid and Negroid races.

Patients with renal failure

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

Patients with liver failure

In patients with different stages of liver failure, there was no increase in T½ of rosuvastatin in patients with a score of 7 or less on the Child-Pugh scale. Two patients with grades 8 and 9 on the Child-Pugh scale showed an increase in T½, at least 2 times. Experience with rosuvastatin in patients with a score above 9 on the Child-Pugh scale is absent.

Genetic polymorphism

HMG-CoA reductase inhibitors, including rosuvastatin, bind to the transport proteins OATP1B1 (a polypeptide of organic anion transport that participates in the capture of statins by hepatocytes) and BCRP (efflux transporter). In carriers of the SLC01B1 (OATP1B1) C.521CC and ABCG2 (BCRP) C.421AA genotypes, there was an increase in exposure (AUC) to rosuvastatin 1.6 and 2.4 times, respectively, compared with the SLC01B1 C.521TT and ABCG2 C.421CC genotypes .

Indications for use

Equamer is indicated as a replacement therapy in adult patients, whose condition is already adequately controlled by taking amlodipine, lisinopril and rosuvastatin in the same doses as in Equamer when treating arterial hypertension and concomitant dyslipidemia:

    primary hypercholesterolemia (Pa type according to Fredrickson classification, with the exception of familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type Fredrickson classification Pb) when diet and other non-drug methods (for example, exercise, weight loss) are insufficient;
    familial homozygous hypercholesterolemia, when diet or other lipid-lowering therapy (for example, LDL-apheresis) is not effective enough;
    hypertriglyceridemia (type IV according to Fredrickson's classification).

Contraindications for Equamer

    Hypersensitivity to amlodipine or other dihydropyridine derivatives.
    Hypersensitivity to lisinopril or other ACE inhibitors.
    Hypersensitivity to rosuvastatin.
    Hypersensitivity to any of the excipients of Equamer.
    Angioedema in history, including the use of ACE inhibitors.
    Hereditary or idiomatic angioedema.
    Severe arterial hypotension (systolic blood pressure less than 90 mm Hg. Art.).
    Obstruction of the excretory tract of the left ventricle (including severe aortic stenosis).
    Hemodynamically unstable heart failure after acute myocardial infarction.
    The simultaneous use of Equamer with aliskiren-containing drugs in patients with diabetes mellitus or renal insufficiency (GFR less than 60 ml / mip / 1.73 m2).
    Liver disease in the active phase, including a persistent increase in transaminase activity in serum, as well as any increase in transaminase activity (more than 3 times compared with the upper limit of normal).
    Severe renal dysfunction (CC less than 30 ml / min).
    Myopathy
    Simultaneous reception of cyclosporine.
    Predisposition to the development of myotoxic complications.
    In women: pregnancy, breastfeeding period, lack of adequate methods of contraception.
    Children's age up to 18 years (efficiency and safety are not established).
    Lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Patients with liver failure

Experience with rosuvastatin in patients with a score above 9 on the Child-Pugh scale is absent (see the Pharmacokinetics section).

Carefully

Aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, hypotension, cerebrovascular diseases (including cerebrovascular insufficiency), ischemic heart disease, coronary insufficiency, nonischemic etiology of CHF III-IV functional class NYHA classification, acute myocardial infarction (and within 1 month after it), unstable stenocardia, sick sinus syndrome (severe tachycardia for bradycardia), severe autoimmune systemic diseases of the connector Noi fabrics including systemic lupus erythematosus, scleroderma), inhibition of bone marrow hematopoiesis, diabetes mellitus, hyperkalemia, bilateral renal artery stenosis, single kidney artery stenosis, kidney transplantation, kidney transplantation, mild to moderate severity (CK 30-80 ml / min), azotemia, primary aldosteronism, diet with limitation of table salt, conditions accompanied by a decrease in the volume of circulating blood (including vomiting, diarrhea), old age, mild liver failure (5-6 point in the Child-Pugh scale) and moderate severity (7-9 points on the Child-Pugh scale), hypothyroidism, personal or family history of hereditary muscular diseases and previous history of muscle toxicity when using other HMG-CoA reductase inhibitors or fibrates, abuse alcohol, conditions in which an increase in plasma concentration of rosuvastatin is noted, race (Mongoloid race), simultaneous use of fibrates, history of liver disease, sepsis, extensive surgical interventions, injuries, severe ie metabolic, endocrine or water-electrolyte disorders, or uncontrolled seizures.

Use Equamer during pregnancy and breastfeeding

Pregnancy

Acadamer is contraindicated during pregnancy.
Adequate strictly controlled clinical studies on the action of Equamer during pregnancy have not been conducted.
Acceptance of ACE inhibitors in the second and third trimesters of pregnancy can cause death of the fetus and newborn. Perhaps the development of oligohydramnios during pregnancy, as well as hypoplasia of the bones of the skull, deformation of the bones of the skull and face, lung hypoplasia and impaired development of the kidneys in the newborn.
Since cholesterol and other cholesterol biosynthesis products are important for fetal development, the potential risk of inhibiting HMG-CoA reductase exceeds the benefits of rosuvastatin during pregnancy.
Women of reproductive age should use adequate methods of contraception. If pregnancy occurs during the course of therapy, Equamer should be immediately discontinued and, if necessary, alternative treatment should be prescribed.
Do not start therapy with Equamer during pregnancy. When planning pregnancy, it is necessary to switch to alternative therapy with a proven safety profile during pregnancy.

Breastfeeding period

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

Fertility

Adequate strictly controlled clinical studies on the effect of Equamer on fertility have not been conducted.

Dosage and administration

Mode of application

Equamer can be taken regardless of mealtime.

Doses

As a rule, the fixed-dose combination drug is not suitable for initial therapy.
The recommended dose of Equamer is 1 capsule per day. The maximum daily dose is 1 capsule.
If a dose adjustment is necessary, dose titration should be carried out using amlodipine, lisinopril and rosuvastatin separately.

Patients with renal failure

During therapy with Equamer, the kidney function, the content of potassium and sodium in the blood plasma should be monitored. In case of deterioration in renal function, Equamer should be canceled. Such patients are recommended individual selection of doses of individual active ingredients. The use of the drug Equamer in patients with severe renal insufficiency is contraindicated in all vines (see section “Contraindications”),

Patients with liver failure

Equamer is contraindicated in patients with active liver disease and in patients with severely impaired liver function (more than 9 points on the Child-Pugh scale) (see the “Contraindications” section).

Children and teenagers (under 18)

The safety and efficacy of Equamer in children and adolescents has not been established.

Elderly patients (over 65)

In elderly patients, Equamer should be used with caution.
In clinical studies, no data were obtained on the change in the efficacy or safety profile of amlodipine, lisinopril or rosuvastatin, depending on age.

Race

When studying the pharmacokinetic parameters of rosuvastatin in patients belonging to different races, there was an increase in the systemic concentration of rosuvastatin in the blood plasma among patients of the mongoloid race (see the section "Special Instructions"). This fact should be taken into account when prescribing Equamer to this group of patients. When prescribing rosuvastatin in a dose of 10 mg and 20 mg, the recommended starting dose of rosuvastatin for patients of the Mongoloid race should be 5 mg.

Genetic polymorphism

In carriers of the SLC01B1 genotypes (OATP1B1) C.521CC and ABCG2 (BCRP) C.421AA, there was an increase in exposure (AUC) to rosuvastatin compared to the carriers of the SLC01B1 C.521CC genotypes and ABCG2 C.421CC. For patients with genotypes p.521CC and C.421AA, the recommended maximum dose of rosuvastatin is 20 mg per day (see the Pharmacokinetics section).

Concomitant therapy

Rosuvastatin binds to various transport proteins (in particular, OATP1B1 and BCRP). When rosuvastatin is used together with medications (such as cyclosporine, some human immunodeficiency virus (HIV) protease inhibitors, including a combination of ritonavir with atazanavir, lopinavir and / or tipranavir), the concentration of rosuvastatin in the blood plasma may increase due to interaction with transport proteins the risk of myopathy (including rhabdomyolysis) (see the sections “Special Instructions” and “Interaction with Other Medicines”). In such cases, the possibility of prescribing alternative therapy or temporary discontinuation of rosuvastatin should be evaluated. If the use of the above preparations is necessary, the ratio of the benefits and risks of concomitant therapy with rosuvastatin should be evaluated and the possibility of reducing its dose should be considered (see the section "Interaction with Other Medicines").

Side effects of Equamer

Adverse adverse reactions are presented according to system-organ classes according to the MedDRA classification and with the frequency of occurrence:
Very often - 1/10 of appointments (> 10%)
Often - 1/100 appointments (> 1%, but <10%)
Infrequently - 1/1000 appointments (> 0.1%, but <1%)
Rarely - 1 / 10,000 appointments (> 0.01%, <0.1% each)
Very rarely - less than 1/10000 appointments (<0.01%)
Frequency unknown - insufficient data to estimate development frequency.
Within each group, adverse reactions are distributed in order of decreasing importance.
With separate treatment with amlodipine, lisinopril and rosuvastatin, the following undesirable adverse reactions were reported:

Amlodipine

Violations of the blood and lymphatic system
Very rarely: thrombocytopenic purpura, leukopenia, thrombocytopenia.
Immune system disorders
Infrequently: pruritus, rash (including erythematous and maculopapular rash, urticaria);
Very rare: angioedema, erythema multiforme.
Metabolic and nutritional disorders
Very rare: hyperglycemia.
Mental disorders
Infrequently: mood lability, unusual dreams, anxiety, depression, anxiety;
Very rarely: apathy, agitation, amnesia.
Nervous system disorders
Often: headache, dizziness, fatigue, drowsiness;
Infrequently: asthenia, malaise, hypesthesia, paresthesia, peripheral neuropathy, tremor, muscle rigidity, insomnia, taste perversion;
Seldom: spasms;
Very rarely: migraine, increased sweating, ataxia, parosmia.
Violations by the organ of vision
Infrequently: diplopia, disturbance of accommodation, xerophthalmia, conjunctivitis, pain in manholes, impaired vision.
Disturbances from an organ of hearing and labyrinth disturbances
Infrequently: tinnitus.
Heart disorders
Often: heart palpitations;
Very rarely: development or exacerbation of chronic heart failure, cardiac arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction, chest pain.
Vascular disorders
Often: peripheral edema (ankles and feet), "hot flashes";
Infrequently: pronounced decrease in blood pressure;
Very rare: fainting, vasculitis, orthostatic hypotension.
Disorders of the respiratory system, chest and mediastinum
Infrequently: shortness of breath, rhinitis, nosebleeds;
Very rarely: cough.
Disorders of 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;
Very rarely: pancreatitis, gastritis.
Disorders of the liver and biliary tract
Very rarely: jaundice (usually cholestatic), hyperbilirubinemia, increased activity of liver transaminases, hepatitis.
Violations of the skin and subcutaneous tissues
Rarely: dermatitis;
Very rarely: alopecia, xerodermia, “cold” sweat, impaired skin pigmentation.
Disorders of the musculoskeletal and connective tissue
Infrequently: arthralgia, muscle cramps, myalgia, back pain, arthrosis;
Rarely: myasthenia.
Kidney and urinary tract disorders
Infrequently: frequent urination, painful urination, nocturia;
Very rare: dysuria, polyuria.
Violations of the genital and breast
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
Seldom: decrease in hemoglobin and hematocrit;
Very rarely: inhibition of bone marrow function, lymphadenopathy, leukopenia, neutropenia, agranulocytosis, thrombocytopenia, hemolytic anemia, anemia;
Frequency unknown: erythropenia.
Immune system disorders
Infrequently: skin rash, itching;
Rarely: angioedema of the face, extremities, lips, tongue, epiglottis and / or larynx;
Very rarely: intestinal angioedema, autoimmune diseases, increased titer of antinuclear antibodies, increased erythrocyte sedimentation rate (ESR);
Frequency unknown: eosinophilia, leukocytosis, fever (there are reports of the development of lupus-like syndrome, which may include fever, myalgia, arthralgia / arthritis, an increase in antinuclear antibody titer, an increase in ESR, eosinophiligo, leukocytosis, may also develop a rash reaction, a reaction, a reaction, a reaction, a reaction, a reaction, an erythrocyte syndrome, an increase in ESR, eosinophiligo, leukocytosis, may develop a reaction, a reaction, a reaction, a ESR, an erythrocyte sedimentation rate, an increase in ESR, eosinophiligo, leukocytosis, may also develop a rash reaction, a reaction, a ESR, an erythrocyte sedimentation rate, an increase in ESR, eosinophiligo, leukocytosis, may also develop a rash, a reaction, a reaction, a reaction, a reaction, a reaction, a reaction, a reaction, a reaction, etc. skin manifestations).
Endocrine Disorders
Frequency unknown: inadequate secretion of antidiuretic hormone syndrome.
Metabolic and nutritional disorders
Very rare: hypoglycemia.
Mental disorders
Often: sleep disturbance;
Infrequently: mood lability;
Rarely: confusion;
Frequency unknown: confusion, depression.
Nervous system disorders
Often: dizziness, headache;
Infrequently: paresthesia, drowsiness;
rarely: asthenic syndrome;
Frequency unknown: syncope, convulsive twitching of the muscles of the face and limbs.
Heart disorders
Infrequently: chest pain, myocardial infarction (due to a pronounced decrease in blood pressure in high-risk patient groups);
Rarely: tachycardia, bradycardia, worsening of the course of chronic heart failure, impaired atrioventricular conduction, rapid heartbeat.
Vascular disorders
Often: pronounced decrease in blood pressure;
Infrequently: violation of cerebral circulation (due to pronounced decrease in blood pressure / high-risk patient groups), Raynaud's syndrome;
Rarely: orthostatic hypotension;
Frequency unknown: vasculitis.
Disorders of the respiratory system, chest and mediastinum
Often: "dry" cough, sinusitis, allergic alveolitis / eosinophilic pneumonia;
Infrequently: rhinitis;
Very rarely: bronchospasm;
Frequency unknown: shortness of breath.
Disorders of the digestive system
Infrequently: dyspepsia, taste perversion, abdominal pain;
Rarely: dryness of the oral mucosa;
Very rarely: pancreatitis;
Frequency unknown: anorexia.
Disorders of the liver and biliary tract
Often: liver failure;
Very rare: hepatocellular and cholestatic jaundice, hepatitis.
Violations of the skin and subcutaneous tissues
Infrequently: skin rash, itching;
Seldom: urticaria, alopecia, psoriasis, photosensitization;
Very seldom: increased sweating, pemphigus, Stevens-Johnson syndrome, toxic epidermal necrolysis, exudative erythema multiforme, skin pseudolymphoma.
Disorders of the musculoskeletal and connective tissue
Frequency unknown: myalgia, arthralgia / arthritis.
Kidney and urinary tract disorders
Often: impaired renal function;
Rarely: acute renal failure, uremia;
Very rarely: oliguria, anuria;
Frequency unknown: proteinuria.
Violations of the genital and breast
Infrequently: decrease in a potentiality;
Rarely: gynecomastia.
Impact on the results of laboratory and instrumental studies
Infrequently: hyperkalemia, hyponatremia, increased concentration of urea and creatinine in blood serum;
Seldom: increase in activity of "liver" enzymes, hyperbilirubinemia.
With simultaneous use of inhibitors of BLP and gold preparations for intravenous administration (sodium aurothiomalate), a symptom complex has been described, including facial flushing, nausea, vomiting and a decrease in blood pressure.

Rosuvastatin

The side effects observed when taking rosuvastatin are usually slightly pronounced and disappear on their own. As with the use of other inhibitors of HMG-CoA reductase, the frequency of side effects is mostly dose-dependent.
Violations of the blood and lymphatic system
Frequency unknown: thrombocytopenia.
Immune system disorders
Seldom: hypersensitivity reactions, including angioedema.
Endocrine Disorders
Often: type 2 diabetes mellitus (frequency will depend on the presence or absence of risk factors (fasting glucose concentration> 5.6 mmol / l, BMI> 30 kg / m2, an increased concentration of triglycerides, a history of arterial hypertension)).
Mental disorders
Frequency unknown: depression.
Nervous system disorders
Often: headache, dizziness;
Very rarely: polyneuropathy, memory loss or loss;
Frequency unknown: peripheral neuropathy, sleep disturbances (including insomnia and “nightmarish” dreams).
Disorders of the respiratory system, chest and mediastinum
Frequency unknown: cough, shortness of breath.
Disorders of the digestive system
Often: constipation, nausea, abdominal pain;
Rarely: pancreatitis;
Frequency unknown: diarrhea.
Disorders of the liver and biliary tract
Seldom: increase in activity of "liver" transaminases;
Very rare: jaundice, hepatitis.
Violations of the skin and subcutaneous tissues
Infrequently: pruritus, rash, urticaria;
Frequency unknown: Stevens-Johnson syndrome.
Disorders of the musculoskeletal and connective tissue
Often: myalgia;
Rarely: myopathy (including myositis), rhabdomyolysis with or without the development of acute renal failure;
Very rarely: arthralgia;
The frequency is unknown: immune-mediated necrotizing myopathy, tendon diseases, in some cases complicated by rupture, a temporary increase in the activity of creatine phosphokinase (CPK). In the case of increased activity of CPK (more than 5 times compared with the upper limit of the norm), therapy should be suspended (see the section "Special Instructions").
Kidney and urinary tract disorders
Very rarely: hematuria;
Frequency unknown: proteinuria.
Violations of the genital and breast
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

The frequency is unknown: an increase in the concentration of bilirubin, blood glucose, an increase in the concentration of glycosylated hemoglobin, the activity of gamma-glutamyltranspeptidase, alkaline phosphatase, thyroid gland dysfunction.
With the use of some HMG-CoA reductase inhibitors, the following skirt effects were reported:

    sexual dysfunction;
    in extremely rare cases, interstitial lung disease, especially with long-term therapy (see section "Special Instructions").

If any of the side effects indicated in the instructions are aggravated, or you have noticed any other side effects that are not indicated in the instructions, inform your doctor.

Overdose

Amlodipine

Symptoms: marked reduction in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (the risk of severe and persistent arterial hypotension, including the development of shock and death).
Treatment: gastric lavage, the appointment of activated carbon (especially in the first 2 h after overdose), maintaining the function of the cardiovascular system, the elevated position of the lower extremities, control functions of the cardiovascular and respiratory systems, control of circulating blood volume (BCC) and diuresis. To restore vascular tone - the use of vasoconstrictor agents (in the absence of contraindications to their use); to eliminate the effects of calcium channel blockade - intravenous calcium gluconate. Hemodialysis is ineffective.

Lisinopril

Symptoms: marked reduction in blood pressure, dry mouth, drowsiness, urinary retention, constipation, anxiety, irritability, renal dysfunction, water and electrolyte balance, tachycardia, bradycardia, collapse, hyperventilation of the lungs, dizziness.
Treatment: symptomatic therapy, intravenous administration of 0.9% sodium chloride solution and, if possible, the use of vazopressorov, control of blood pressure, water and electrolyte balance. With sustainable bradycardia, an artificial pacemaker can be set. Hemodialysis may be used (see instructions for patients on hemodialysis in the Special Instructions section).

Rosuvastatin

When several daily doses are taken simultaneously, the pharmacokinetic parameters of rosuvastatin do not change.
There is no specific treatment for an overdose of rosuvastatin. In case of 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 control liver function and CPK activity. It is unlikely that hemodialysis will be effective.

Interaction with other drugs

Amlodipine

Amlodipine can be safely used for the treatment of arterial hypertension along with thiazide diuretics, alpha-blockers, beta-blockers or ACE inhibitors. In patients with stable angina, amlodipine can be combined with other antianginal agents, for example, with prolonged or short-acting nitrates, beta-blockers.
Unlike other BMCC, clinically significant interaction of amlodipine (III generation of BMCC) was not found when combined with nonsteroidal anti-inflammatory drugs (NSAIDs), including indomethacin. It is possible to enhance the antianginal and antihypertensive effects of BMCA when used together with thiazide and “loop” diuretics, ACE inhibitors, beta-blockers and nitrates, as well as enhance their antihypertensive effect when combined with alpha-blockers, neuroleptics.
Although in the study of amlodipine, a negative inotropic effect was usually not observed, however, some BMCCs may increase the severity of the negative inotropic effect of antiarrhythmic drugs that cause prolongation of the QT interval (for example, amiodarone and quinidine).
Amlodipine can also be safely used simultaneously with antibiotics and typoglycemic agents for oral administration.
A single dose of 100 mg of sildenafil in patients with essential hypertension does not affect the parameters of amlodipine pharmacokinetics.
The 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 the pharmacokinetics of etorvastatin.
Simvastatin: simultaneous repeated use of amlodipine in a dose of 10 mg and simvastatin in a dose of 80 mg leads to an increase in the exposure of simvastatin by 77%. In such cases, the dose of simvastatin should be limited to 20 mg.
Rosuvastatin: with simultaneous repeated use of amlodipine at a dose of 10 mg and rosuvastatin at a dose of 20 mg, an increase of about 28% AUC and 31% Ctau rosuvastatin was observed. The exact mechanism of interaction is unknown. This effect is not expected to have clinical significance with the daily use of Ekvamer®, since it is indicated only to those patients who already receive lisinopril, amlodipine, and rosuvastatin in the same doses as in this combination.
Ethanol (alcohol-containing beverages): Amlodipine, when taken once and again at a dose of 10 mg, does not affect the pharmacokinetics of ethanol.
Antivirals (ritonavir): increases plasma concentrations of BCCA. including amlodipine.
Neuroleptics and isoflurane: increased antihypertensive effect of dihydropyridine derivatives.
Calcium preparations can reduce the effect of BCCA.
When combined with lithium preparations of BCCA (data are not available for amlodipine), it is possible to increase the manifestation of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).
Studies on the simultaneous use of amlodipine and cyclosporine in healthy volunteers and all groups of patients, with the exception of patients after kidney transplantation, have not been conducted. 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 cyclosporine 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 should be used simultaneously. Does not affect the serum concentration of digoxin and its renal clearance.
It has no significant effect on the effect of warfarin (prothrombin time).
Cimetidine does not affect the pharmacokinetics of amlodipine.
In in vitro studies, amlodipine does not affect the binding to plasma proteins of digoxin, phenytoin, warfarin, and indomethacin.
Grapefruit juice: a single dose of 240 mg of grapefruit juice and 10 mg of amlodipine orally is not accompanied by a significant change in the pharmacokinetics of amlodipine. However, it is not recommended to use grapefruit juice and amlodipine at the same time, since the genetic polymorphism of the CYP3A4 isoenzyme may increase the bioavailability of amlodipine and, consequently, increase the antihypertensive effect.
Aluminum- or magnesium-containing aptacids: their single dose does not have a significant effect on the pharmacokinetics of amlodipine.
CYP3A4 isoenzyme inhibitors: with simultaneous use of diltiazem at a dose of 180 mg and amlodipine at a dose of 5 mg in elderly patients (69 to 87 years) with arterial hypertension, an increase in systemic exposure to amlodipine is noted by 57%.

The simultaneous use of amlodipine and erythromycin in healthy volunteers (from 18 to 43 years old) does not lead to significant changes in the exposure to amlodipine (an increase in AUC by 22%). Although the clinical significance of these effects is not completely clear, they may be more pronounced in older patients.
Potent inhibitors of the isoenzyme CYP3A4 (for example, ketoconazole, itraconazole) can lead to an increase in the concentration of amlodipine in the blood plasma to a greater extent than diltiazem. Amlodipine and CYP3A4 isoenzyme inhibitors should be used with caution.
Inductors of isoenzyme SURZA4: there are no data on the effect of inducers of CYP3A4 isoenzyme on the pharmacokinetics of amlodipine. Blood pressure should be carefully monitored with simultaneous use of amlodipine and CYP3A4 isoenzyme inducers.

Lisipopril

When used simultaneously with potassium-sparing diuretics (spironolactone, eplerenone (a derivative of spironolactone), triamterene, amiloride), potassium preparations, potassium-containing salt substitutes, the risk of hyperkalemia increases, especially in patients with impaired renal function.
With simultaneous use with diuretics - a pronounced decrease in blood pressure.
The simultaneous use of lisinopril with beta-blockers, slow calcium channel blockers, diuretics, tricyclic antidepressants / neuroleptics enhances the severity of the antihypertensive effect.
With simultaneous use with nonsteroidal anti-inflammatory drugs (indomethacin, etc.), including acetylsalicylic acid> 3 g / day, estrogen, as well as adrenergic mimetics - a decrease in the antihypertensive effect of lisinopril.
With simultaneous use with lithium preparations - slow lithium removal from the body.
Simultaneous use with antacids and Kolestiramine slows down the absorption in the gastrointestinal tract.
Ethanol enhances the effect of lisinopril.
The double blockade of the renin-angiotensin-aldosterone system (RAAS) through the simultaneous use of angiotensin-II receptor antagonists (ARA II), ACE inhibitors or aliskiren is associated with an increased incidence of arterial hypotension, hyperkalemia and impaired renal function (including kidney failure) by compared with the use of a single drug acting on the RAAS.
When used simultaneously with insulin and hypoglycemic agents for oral administration increases the risk of hypoglycemia.
With the simultaneous use of ACE inhibitors and gold preparations for intravenous administration (sodium aurothiomalate), a symptom complex has been described, including facial flushing, nausea, vomiting and a decrease in blood pressure.
The simultaneous use of lisinopril with acetylsalicylic acid as an antiplatelet agent, thrombolytic agents, beta-blockers and / or nitrates is not contraindicated.
Concurrent use with selective serotonin reuptake inhibitors can lead to severe hyponatremia.
Simultaneous use with allopurinol, procainamide, cytotoxic drugs may increase the risk of leukopenia.

Rosuvastatin

Effect of other drugs on rosuvastatin
Transport protein inhibitors: Rosuvastatin binds to certain transport proteins, in particular, OATP1B1 and BCRP. The concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in plasma plasma concentration of rosuvastatin and an increased risk of myopathy (see Table 3 and the sections “Dosage and administration” and “Special instructions”).
Cyclosporine: with simultaneous use of rosuvastatin and cyclosporine, AUC of rosuvastatin was, on average, 7 times higher than that observed in healthy volunteers (see the “Contraindications” section). It does not affect the plasma concentration of cyclosporine. Rosuvastatin is contraindicated in patients taking cyclosporine (see section "Contraindications").
Human Immunodeficiency Virus Protease Inhibitors: Although the exact mechanism of interaction is unknown, co-administration of HIV protease inhibitors can lead to a significant increase in rosuvastatin exposure.
A pharmacokinetic study of simultaneous use of 20 mg of rosuvastatin and a combined preparation containing two HIV progease inhibitors (400 mg of lopinavir / 100 mg of rigonavir) in healthy volunteers resulted in an approximately twofold and fivefold increase in AUC (0-24) and Cmax of rosuvastatin, respectively. Therefore, the concomitant use of rosuvastatin and HIV protease inhibitors in the treatment of patients with human immunodeficiency virus is not recommended (see the section "Special Instructions" and Table 3).
Gemfibrozil and other hypolipidemic agents: the combined use of rosuvastatin and gemfibrozil leads to an increase in 2 times the maximum concentration of rosuvastatin in the blood plasma, as well as an increase in the AUC of rosuvastatin (see the section "Special Instructions"). Based on data on specific interactions, TC expects a pharmacokinetically significant interaction with fenofibrate, possibly pharmacodynamic interaction.
Gemfibrozil, fenofibrate, other fibrates and nicotinic acid in lipid-lowering doses (more than 1 g / day) increase the risk of myopathy, while being used with HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy and when used in monotherapy (see section "Special instructions").
Ezetimibe: the simultaneous use of rosuvastatin at a dose of 10 mg and ezetimibe at a dose of 10 mg was accompanied by an increase in the AUC of rosuvastatin in patients with hypercholesterolemia (see table 3). An increase in the risk of side effects due to the pharmacodynamic interaction between rosuvastatin and ezetimib cannot be ruled out.
Antacids: the simultaneous use of rosuvastatin and suspensions of antacids containing aluminum or magnesium hydroxide, reduces the plasma concentration of rosuvastatin by about 50%. This effect is less pronounced if antacids are applied 2 hours after taking rosuvastatin. The clinical significance of this interaction has not been studied.
Erythromycin: the simultaneous use of rosuvastatin and erythromycin leads to a decrease in AUC (0-24) of rosuvastatin by 20% and Cmax of rosuvastatin by 30%. Such an interaction may occur as a result of increased intestinal motility caused by taking erythromycin.
Fuzidova acid: studies on the interaction of rosuvastatin and fusidic acid was not conducted. As with the use of other HMG-CoA reductase inhibitors, postmarketing reports were received of cases of rhabdomyolysis with the combined use of rosuvastatin and fusidic acid. It is necessary to closely monitor patients. If necessary, it is possible to temporarily stop taking rosuvastatin.
Cytochrome P450 isoenzymes: the results of in vivo and in vitro studies have shown that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes.
In addition, rosuvastatin is a weak substrate for these enzymes. Therefore, the 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 (an inhibitor of CYP2C9 and CYP3A4 isoenzymes) and ketoconazole (an inhibitor of CYP2A6 and CYP3A4 isoenzymes).
Drug interactions that require dose adjustment of rosuvastatin (see table 3)
The dose of rosuvastatin should be adjusted, if necessary, its joint use with drugs that increase the exposure to rosuvastatin. If exposure is expected to increase by 2 times or more, the initial dose of rosuvastatin should be 5 mg once a day. The maximum daily dose of rosuvastatin should also be adjusted so that the expected exposure to rosuvastatin does not exceed that for a dose of 40 mg taken without the simultaneous prescription of drugs interacting with rosuvastatin. For example, the maximum daily dose of rosuvastatin, while using gemfibrozil, is 20 mg (1.9 times increase in exposure), with ritonavir / atazanavir - 10 mg (3.1 times increase in exposure).
The effect of rosuvastatin on other drugs
Vitamin K antagonists: As with other HMG-CoA reductase inhibitors, initiating rosuvastatin therapy or increasing the dosage of rosuvastatin in patients receiving vitamin K antagonists (for example, warfarin or other coumarin anticoagulants) may increase the international normalized ratio ( Mho). Canceling or lowering the dose of rosuvastatin can cause a decrease in Ml 10. In such cases, MHO should be monitored.
Oral contraceptives / hormone replacement therapy: the simultaneous use of rosuvastatin and oral contraceptives increases the AUC of these ni estradiola and AUC norgestrel by 26% and 34%, respectively. Such an increase in plasma concentration should be taken into account when selecting the dose of oral contraceptives. Pharmacokinetic data on the simultaneous use of rosuvastatin and hormone replacement therapy are not available. We cannot exclude a similar effect with the simultaneous use of rosuvastatin and hormone replacement therapy. However, this combination was widely used during clinical trials and was well tolerated by patients.
Other medications: the clinically significant interaction of rosuvastatin with digoxin is not expected.

special instructions

If you have been hospitalized, tell your doctor that you are taking Equamer.
If you also forgot to take the capsule of Equamer, wait and take the next capsule at the usual time. Do not take a double dose to make up the missed dose.
At use of the preparation Ekvamer® it is necessary to consider recommendations about use of separate components of a preparation, described in detail below.

Amlodipine

It is necessary to maintain dental hygiene and observation at the dentist (to prevent pain, bleeding and gum hyperplasia). Older patients may increase T½ and decrease the clearance of amlodipine. Changing doses is not required, but more careful observation 5 is needed in patients of this category.
The efficacy and safety of the use of amlodipine in hypertensive crisis has not been established.
Despite the absence of withdrawal syndrome in BMCC, it is advisable to stop the treatment with amlodinine, gradually reducing the dose of Equamer.
Amidipine was used in patients with CHF of non-ischemic genesis of functional class III and IV, according to the NYIIA classification, 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 pronounced decrease in blood pressure occurs with a decrease in BCC, caused by diuretic therapy, a decrease in salt in food, dialysis, diarrhea, and vomiting (see the sections "Interaction with Other Drugs" and "Side Effects"). In patients with CHF, both in the presence of concomitant renal failure and in its absence, symptomatic arterial hypertension may develop. It was more commonly 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 begin under the strict supervision of a physician (with caution, select the dose of lisinopril and diuretics). Similar rules should be followed when prescribing lisinopril to patients with ischemic heart disease, cerebrovascular insufficiency, in which a sharp decrease in blood pressure can lead to myocardial infarction or stroke.
In the case of a pronounced decrease in the patient's blood pressure, the patient should be laid down and, if necessary, compensated for the loss of fluid (intravenous infusion of 0.9% sodium chloride solution). The transient hypotensive reaction is not a contraindication for taking the next dose of lisinopril.
When lisinopril is used in some patients with XCH, but with normal or decreased blood pressure, there may be a decrease in blood pressure, which is usually not a reason to stop therapy. If arterial hypotension becomes symptomatic, it is necessary to reduce the dose or discontinue therapy with lisinopril.
Patients who are at risk of developing symptomatic hypotension (who are on a diet with salt restriction or salt-free diet) with or without hyponatremia, as well as in patients who received high doses of diuretics, must compensate for the loss of fluids and salts before starting treatment.
It is necessary to control the antihypertensive effect of the initial dose of lisinopril.
Aortic and mitral valve stenosis / hypertrophic obstructive cardiomyopathy
As in the case of other ACE inhibitors, lisinopril should be administered with caution to patients with mitral valve stenosis and obstruction of the left ventricular excretory tract (aortic stenosis or hypertrophic obstructive cardiomyopathy).
Acute myocardial infarction
The use of standard therapy (thrombolytics, acetylsalicylic acid as an antiplatelet agent, beta-blockers) is shown.
Lisinopril may be used in conjunction with the intravenous administration of nitroglycerin or with the use of transdermal systems nitroglycerin.
Lysinopril therapy should not be initiated in patients with acute myocardial infarction, who are at risk of