Ekvamer [Equamer] capsules 10mg+20mg+20mg, 30pcs

Composition

1 capsule contains: Active ingredient:  amlodipine bezylate – 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%, talc 14.8%, iron oxide yellow dye 1.5%), solid gelatin capsule – 97 mg (contains: blue patent dye 0.02933%, azorubin dye 0.3067%, sunset yellow dye 0.02355%, titanium dioxide 3.7037%, gelatin up to 100%).

Pharmacological action

Combined antihypertensive and lipid-lowering drug. Ekvamer® contains three active ingredients: amlodipine, lisinopril and rosuvastatin. The mechanism of action of Ekvamer® is based on the pharmacological properties of the active ingredients.

Amlodipine

Dihydropyridine derivative-slow calcium channel blocker (BMCC), has antihypertensive and antianginal effects. Blocks slow calcium channels, reduces the transmembrane transfer of calcium ions into the cell (more to vascular smooth muscle cells than to cardiomyocytes).

The antianginal effect is caused by dilation of the coronary and peripheral arteries and arterioles:

– with angina reduces the severity of myocardial ischemia; expanding peripheral arterioles, reduces OPSS, reduces afterload on the heart, reduces the need for myocardial oxygen;- dilating the coronary arteries and arterioles in unchanged and ischemic areas of the myocardium, increases oxygen supply to the myocardium (especially in vasospastic angina); prevents spasm of the coronary arteries (including those caused by smoking). In patients with stable angina, a single daily dose increases exercise tolerance, slows the development of angina attacks and ST-segment ischemic depression, reduces the frequency of angina attacks and consumption of nitroglycerin and other nitrates.

It has a long-term dose-dependent antihypertensive effect. The antihypertensive effect is due to the direct vasodilating effect on vascular smooth muscles. In arterial hypertension, a single dose provides a clinically significant reduction in blood pressure for 24 hours (in the patient’s lying and standing positions).

Orthostatic hypotension with the use of amlodipine is quite rare. Amlodipine does not cause a decrease in exercise tolerance, left ventricular ejection fraction. Reduces the degree of left ventricular myocardial hypertrophy. It does not affect the contractility and conduction of the myocardium, does not cause a reflex increase in heart rate, inhibits platelet aggregation, increases GFR, and has a weak natriuretic effect. In diabetic nephropathy, it does not increase the severity of microalbuminuria. It does not have any adverse effect on the metabolism and concentration of plasma lipids, 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 (including coronary atherosclerosis with damage to one vessel and up to stenosis of 3 or more arteries, carotid artery atherosclerosis), who have suffered a myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA) or in patients with angina, the use of amlodipine prevents an increase in the thickness of the intima-media complex of the carotid arteries, reduces mortality from myocardial infarction, stroke, PTCA, coronary artery bypass grafting; reduces the number of hospitalizations for unstable angina and the progression of chronic heart failure (CHF); reduces the frequency of interventions aimed at restoring coronary blood flow.

It does not increase the risk of death or development of complications and deaths in patients with CHF (NYHA functional class III-IV) during therapy with digoxin, diuretics and ACE inhibitors. In patients with CHF (NYHA functional class III-IV) of non-ischemic etiology, amlodipine is likely to cause pulmonary edema.

Lisinopril

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 the synthesis of prostaglandins. Reduces OPSS, blood pressure, preload, pressure in the pulmonary capillaries, causes an increase in minute blood volume and increased myocardial tolerance to physical exertion in patients with CHF. Dilates the arteries to a greater extent than the veins. Some of the effects are attributed to effects on the tissue renin-angiotensin system. With prolonged use, hypertrophy of the myocardium and arterial walls of the resistive type decreases.

Improves blood supply to the ischemic myocardium.

ACE inhibitors prolong life expectancy in patients with CHF, slow the progression of left ventricular dysfunction in patients who have had a myocardial infarction without clinical manifestations of heart failure. The onset of action is 1 hour after ingestion. The maximum hypotensive effect is determined after 6-7 hours and persists for 24 hours. With arterial hypertension, the effect is noted in the first days after the start of treatment, a stable effect develops after 1-2 months. When lisinopril was abruptly discontinued, there was no marked increase in blood pressure. In addition to lowering blood pressure, lisinopril reduces albuminuria. In patients with hyperglycemia, it helps to normalize the function of damaged glomerular endothelium. Lisinopril does not affect the concentration of glucose in the blood in patients with diabetes mellitus and does not lead to an increase in cases of hypoglycemia.

Rosuvastatin

Selective, competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a cholesterol precursor. The main target of rosuvastatin action is the liver, where cholesterol synthesis and LDL catabolism are carried out.

Rosuvastatin increases the number of LDL receptors on the surface of hepatocytes, increasing the uptake and catabolism of LDL, which, in turn, leads to inhibition of VLDL synthesis, thereby reducing the total amount of LDL and VLDL.

Rosuvastatin reduces the elevated concentration of LDL cholesterol (LDL-C), total cholesterol (Cs) and triglycerides (TG) and increases the concentration of high-density lipoprotein cholesterol (HDL-C), and also reduces the concentration of apolipoprotein B (apoB), HDL-C, VLDL-C, TG-VLDL and increases the concentration of apolipoprotein A-I (ApoA-I). I) (see tables 1 and 2), reduces the LDL-C/HDL-C ratio, total Cholesterol/HDL-C, Non-HDL-C/HDL-C, and the apoB/ApoA-I ratio.

The therapeutic effect appears within 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 4 weeks and is maintained with regular use.

Indications

Ekvamer® is indicated as a replacement therapy in adult patients whose condition is already adequately controlled by taking amlodipine, lisinopril and rosuvastatin at the same doses as in Ekvamer®, in the treatment of arterial hypertension and concomitant dyslipidemia:

• primary hypercholesterolemia (type PA classification Fredrickson, with the exception of family heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type DRUNK at Fredrickson classification) when diet and other non-pharmacological methods (e. g. exercise, weight reduction) are insufficient;
• family homozygous hypercholesterolemia, when the diet or other Lipetskaya therapy (e. g., LDL apheresis) is not effective enough;
• hypertriglyceridemia (type IV according to the classification of Fredrickson).

Contraindications

• Hypersensitivity to amlodipine or other dihydropyridine derivatives.
• Hypersensitivity to lisinopril or other ACE inhibitors.
• Hypersensitivity to rosuvastatin.
• Hypersensitivity to any of the excipients of the drug.
• Angioedema in the anamnesis, including from the use of ACE inhibitors.
• Hereditary or idiomatic angioedema.
• Severe arterial hypotension (systolic blood pressure less than 90 mm Hg).
• Left ventricular outflow tract obstruction (including severe aortic stenosis).
• Hemodynamically unstable heart failure after acute myocardial infarction.
• Concomitant use of Ekvamer® with aliskiren-containing drugs in patients with diabetes mellitus or renal insufficiency (GFR less than 60 ml / mip/1.73 m%^%2).
• Liver disease in the active phase, including a persistent increase in transaminase activity in the blood serum, as well as any increase in transaminase activity (more than 3 times compared to the upper limit of normal).
• Severe renal impairment (creatinine clearance less than 30 ml / min).
• Myopathy.
• Simultaneous administration of cyclosporine.
• Predisposition to the development of myotoxic complications.
• In women: pregnancy, breast-feeding, lack of adequate methods of contraception.
• Children under 18 years of age (efficacy and safety have not been established).
• Lactose intolerance, lactase deficiency, or glucose-galactose malabsorption.

Patients with hepatic insufficiency There is no experience of using rosuvastatin in patients with a score higher than 9 on the Child-Pugh scale (see the section “Pharmacokinetics”).

With caution, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, arterial hypotension, cerebrovascular diseases (including cerebral circulatory failure), coronary heart disease, coronary insufficiency, non-ischemic heart failure of NYHA functional class III-IV, acute myocardial infarction (and within 1 month after it), unstable angina, sinus node weakness syndrome (pronounced tachycardia (or bradycardia), severe autoimmune systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), bone marrow hematopoiesis suppression, diabetes mellitus, hyperkalemia, bilateral renal artery stenosis, single kidney artery stenosis, post-kidney transplant condition, mild to moderate renal failure (creatinine clearance 30-80 ml/min), azotemia, primary aldosteronism, diet with a restriction of table salt, conditions associated with a decrease in the volume of circulating blood (including vomiting, diarrhea), old age, mild liver failure (5-6 points on the Child-Pugh scale) and moderate severity (7-9 points on the Child-Pugh scale), hypothyroidism, personal or family history of hereditary muscle diseases and a previous history of muscle toxicity with the use of other HMG-CoA reductase inhibitors or fibrates alcohol abuse, conditions with elevated plasma concentrations of rosuvastatin, race Mongoloid), concomitant use of fibrates, a history of liver disease, sepsis, extensive surgery, injuries, severe metabolic, endocrine or water-electrolyte disorders, or uncontrolled seizures.

Side effects

Undesirable side effects are presented by 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 >Infrequently – 1/1000 appointments (>0.1%, but >Rare – 1/10000 appointments (>0.01%, by default >Very rare – less than 1/10000 appointments (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 significance. The following adverse reactions have been reported with separate treatment with amlodipine, lisinopril and rosuvastatin::

Amlodipine – Blood and lymphatic system disorders Very rare: thrombocytopenic purpura, leukopenia, thrombocytopenia. – Disorders of the immune system: Often: pruritus of the skin, rash (including erythematous and maculopapular rash, urticaria); Very rarely: angioedema, erythema multiforme. – Metabolic and nutritional disorders are very rare: hyperglycemia. – Mental disorders Often: lability of mood, unusual dreams, increased excitability, depression, anxiety; Very rarely: apathy, agitation, amnesia. – Nervous system disorders Often: headache, dizziness, increased fatigue, drowsiness; Infrequently: asthenia, malaise, hypesthesia, paresthesia, peripheral neuropathy, tremor, muscle rigidity, insomnia, taste distortion;Rarely: convulsions;Very rarely: migraine, increased sweating, ataxia, parosmia. – Visual disorders often: diplopia, accommodation disorders, xerophthalmia, conjunctivitis, joint pain, visual impairment. – Hearing disorders and labyrinth disorders often: tinnitus. – Heart disorders Often: increased heart rate; Very rarely: development or worsening 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: marked decrease in blood pressure;Very rarely: fainting, vasculitis, orthostatic hypotension. – Respiratory, thoracic and mediastinal disorders Often: shortness of breath, rhinitis, nosebleeds;Very rarely: cough. Digestive system disorders Often: nausea, abdominal pain; Infrequently: vomiting, constipation, diarrhea, flatulence, dyspepsia, anorexia, dry mouth, thirst;Rarely: gum hyperplasia, increased appetite;Very rarely: pancreatitis, gastritis. – Liver and biliary tract disorders are very rare: jaundice (usually cholestatic), hyperbilirubinemia, increased activity of “hepatic” transaminases, hepatitis. Skin and subcutaneous tissue disorders Rare: dermatitis; Very rare: alopecia, xeroderma, cold sweat, skin pigmentation disorders. -Musculoskeletal and connective tissue disorders Often: arthralgia, muscle cramps, myalgia, back pain, osteoarthritis; Rarely: myasthenia gravis. Renal and urinary tract disorders Often: frequent urination, painful urination, nocturia; Very rarely: dysuria, polyuria. Disorders of the genitals and mammary gland often: erectile dysfunction, gynecomastia. – General disorders and disorders at the injection site often: pain of unspecified localization, increase/decrease in body weight.

Lisinopril-Blood and lymphatic system disorders Rare: decreased hemoglobin and hematocrit; Very rare: bone marrow suppression, lymphadenopathy, leukopenia, neutropenia, agranulocytosis, thrombocytopenia, hemolytic anemia, anemia; Frequency unknown: erythropenia. – Immune system disorders Often: skin rash, pruritus;Rarely: angioedema of the face, extremities, lips, tongue, epiglottis and/or larynx;Very rarely: intestinal angioedema, autoimmune diseases, increased anti-nuclear antibody titer, 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, increased antinuclear antibody titer, increased ESR, eosinophiligo, leukocytosis, and possibly rash, photosensitivity reactions, or other skin manifestations). – Disorders of the endocrine system Frequency unknown: syndrome of inadequate secretion of antidiuretic hormone. – Metabolic and nutritional disorders are 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. – Cardiac disorders Often: chest pain, myocardial infarction (due to a pronounced decrease in blood pressure in high-risk groups of patients); Rarely: tachycardia, bradycardia, worsening of the course of chronic heart failure, violation of atrioventricular conduction, rapid heartbeat. – Vascular disorders Infrequently: marked decrease in blood pressure; Infrequently: cerebrovascular accident (due to a pronounced decrease in blood pressure / high-risk patient groups), Raynaud’s syndrome; Rarely: orthostatic hypotension; Frequency unknown: vasculitis. – Respiratory, thoracic and mediastinal disorders Often: dry cough, sinusitis, allergic alveolitis/eosinophilic pneumonia; Infrequently: rhinitis; Very rarely: bronchospasm; Frequency unknown: shortness of breath. – Disorders of the digestive system: Often: dyspepsia, taste distortion, 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 rarely: hepatocellular and cholestatic jaundice, hepatitis. – Skin and subcutaneous tissue disorders Often: skin rash, pruritus; Rarely: urticaria, alopecia, psoriasis, photosensitization; Very rarely: increased sweating, pemphigus, Stevens-Johnson syndrome, toxic epidermal necrolysis, exudative erythema multiforme, pseudolymphoma of the skin. -Musculoskeletal and connective tissue disorders Frequency unknown: myalgia, arthralgia/arthritis. – Disorders of the kidneys and urinary tract Often: impaired renal function; Rarely: acute renal failure, uremia; Very rarely: oliguria, anuria; Frequency unknown: proteinuria. – Disorders of the genitals and mammary gland often: decreased potency; Rarely: gynecomastia. Influence on the results of laboratory and instrumental studiesnot infrequently: hyperkalemia, hyponatremia, increased serum urea and creatinine concentrations; Rarely: increased activity of “liver” enzymes, hyperbilirubinemia. Concomitant use of LPF inhibitors and intravenous gold preparations (sodium aurothiomalate) has described a symptom complex that includes hyperemia of the facial skin, nausea, vomiting, and a decrease in blood pressure.

Rosuvastatin Side effects observed with rosuvastatin are usually mild and resolve on their own. As with other HMG-CoA reductase inhibitors, the frequency of side effects is mainly dose-dependent. – Disorders of the blood and lymphatic system Frequency unknown: thrombocytopenia. – Immune system disorders Rarely: hypersensitivity reactions, including angioedema.- Endocrine system disorders Often: type 2 diabetes mellitus (the frequency will depend on the presence or absence of risk factors (fasting glucose concentration >5.6 mmol / L, BMI > > 30 kg / m2, elevated triglyceride concentration, a history ofWhen ACE inhibitors and intravenous gold preparations (sodium aurothiomalate) are used simultaneously, a symptom complex is described, including facial skin hyperemia, nausea, vomiting, and a decrease in blood pressure. Concomitant use of lisinopril with acetylsalicylic acid as an antiplatelet agent, thrombolytics, beta-blockers and/or nitrates is not contraindicated. Concomitant use with selective serotonin reuptake inhibitors may result in severe hyponatremia. Concomitant use with allopurinol, procainamide, and cytostatics may increase the risk of leukopenia.

Rosuvastatin Effect of other drugs on Rosuvastatin inhibitors of transport proteins: rosuvastatin binds to some transport proteins, in particular to OATP1 In 1 and BCRP. Concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in the concentration of rosuvastatin in blood plasma and an increased risk of developing myopathy. Cyclosporine: when rosuvastatin and cyclosporine were co-administered, the AUC of rosuvastatin was on average 7 times higher than that observed in healthy volunteers (see section “Contraindications”). It does not affect the plasma concentration of cyclosporine. Rosuvastatin is contraindicated in patients taking cyclosporine. Human immunodeficiency virus protease inhibitors: Although the exact mechanism of interaction is unknown, co-use of HIV protease inhibitors can lead to a significant increase in rosuvastatin exposure. A pharmacokinetic study on the concomitant use of 20 mg rosuvastatin and a combination drug containing two HIV progease inhibitors (400 mg lopinavir/100 mg rigonavir) in healthy volunteers resulted in approximately a twofold and fivefold increase in AUC(0-24) and Cmax of rosuvastatin, respectively. Therefore, simultaneous use of rosuvastatin and HIV protease inhibitors in the treatment of patients with human immunodeficiency virus is not recommended. Gemfibrozil and other lipid-lowering agents: the combined use of rosuvastatin and gemfibrozil leads to a 2-fold increase in the maximum concentration of rosuvastatin in blood plasma, as well as an increase in the AUC of rosuvastatin. Based on specific interaction data, no pharmacokinetically significant interaction with fenofibrate is expected, and a pharmacodynamic interaction is possible. Gemfibrozil, fenofibrate, other fibrates and nicotinic acid in lipid-lowering doses (more than 1 g / day) increase the risk of myopathy when used simultaneously with HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy and when used in monotherapy. Ezetimibe: concomitant use of 10 mg rosuvastatin and 10 mg ezetimibe was associated with an increase in rosuvastatin AUC in patients with hypercholesterolemia. An increased risk of side effects due to the pharmacodynamic interaction between rosuvastatin and ezetimibe cannot be excluded. Antacids: concomitant use 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 applied 2 hours after taking rosuvastatin. The clinical significance of this interaction has not been studied. Erythromycin: concomitant use of rosuvastatin and erythromycin leads to a decrease in AUC(0-24) rosuvastatin by 20% and rosuvastatin Cmax by 30%. This interaction may occur as a result of increased intestinal motility caused by taking erythromycin. Fusidic acid: studies on the interaction of rosuvastatin and fusidic acid have not been conducted. As with other HMG-CoA reductase inhibitors, there have been post-marketing reports of cases of rhabdomyolysis with the combined use of rosuvastatin and fusidic acid. Patients should be closely monitored. If necessary, it is possible to temporarily stop taking rosuvastatin. Cytochrome P450 isoenzymes: 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, rosuvastatin is not expected to interact with other drugs at the level of metabolism involving cytochrome P450 isoenzymes. There was no clinically significant interaction between rosuvastatin and fluconazole (an inhibitor of the CYP2C9 and CYP3A4 isoenzymes) and ketoconazole (an inhibitor of the CYP2A6 and CYP3A4 isoenzymes). Drug interactions that require dose adjustment of rosuvastatin. The dose of rosuvastatin should be adjusted if it is necessary to use it together with drugs that increase exposure to rosuvastatin. If exposure is expected to increase by a factor of 2 or more, the initial dose of rosuvastatin should be 5 mg once daily. 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 concomitant use of drugs that interact with rosuvastatin. For example, the maximum daily dose of rosuvastatin when used concomitantly with gemfibrozil is 20 mg (1.9-fold increase in exposure), with ritonavir/atazanavir-10 mg (3.1-fold increase in exposure).

Effect of rosuvastatin on other vitamin K antagonist drugs: As with other HMG-CoA reductase inhibitors, initiation of rosuvastatin therapy or an increase in the dose of rosuvastatin in patients receiving concomitant vitamin K antagonists (for example, warfarin or other coumarin anticoagulants) may lead to an increase in the international normalized ratio (MHO). Discontinuation or reduction of the rosuvastatin dose may cause a decrease in Ml 10. In such cases, the MHO should be monitored. Oral contraceptives/Hormone replacement therapy: concomitant use of rosuvastatin and oral contraceptives increases the AUC of ethyl estradiol and norgestrel by 26% and 34%, respectively. Such an increase in plasma concentration should be taken into account when selecting the dose of oral contraceptives. There are no pharmacokinetic data on the concomitant use of rosuvastatin and hormone replacement therapy. A similar effect cannot be excluded 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 medicinal products: no clinically significant interaction of rosuvastatin with digoxin is expected.

How to take, course of use and dosage

Ekvamer® can be taken regardless of the meal time. Dosage As a rule, a combination drug with fixed doses is not suitable for initial therapy. Ekvamer® is used as a replacement therapy in adult patients who are already receiving amlodipine, lisinopril and rosuvastatin in the same doses as in this drug. The recommended dose of Ekvamer® is 1 capsule per day. The maximum daily dose is 1 capsule. If dose adjustment is necessary, titration should be performed using amlodipine, lisinopril and rosuvastatin separately. Special patient groups – Patients with renal insufficiency During therapy with Ekvamer®, renal function, potassium and sodium levels in blood plasma should be monitored. If renal function worsens, Ekvamer® should be discontinued. Individual selection of doses of individual active components is recommended for such patients. The use of Ekvamer® in patients with severe renal insufficiency is contraindicated in all doses (see section “Contraindications”), – Patients with hepatic insufficiency Ekvamer® is contraindicated in patients with active liver disease and patients with severe hepatic impairment (more than 9 points on the Child-Pugh scale) (see section “Contraindications”). – Children and teenagers (under 18 years of age)The safety and efficacy of Ekvamer® in children and adolescents has not been established. – Elderly patients (over 65 years of age)In elderly patients, Ekvamer® should be used with caution. In clinical trials, there were no data on changes in the efficacy or safety profile of amlodipine, lisinopril, or rosuvastatin depending on age. 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 Mongolian race was noted. This fact should be taken into account when prescribing Ekvamer® to this group of patients. When prescribing rosuvastatin at a dose of 10 mg and 20 mg, the recommended initial dose of rosuvastatin for patients of the Mongolian race should be 5 mg. – Genetic polymorphis M of carriers of genotypes SLC01B1 (OATR 1 In 1) C. 521CC and ABCG2 (BCRP) C. 421 AA there was an increase in exposure (AUC) to rosuvastatin compared with carriers of genotypes SLC01B1 P. 521 TT and ABCG2 p. 421 SS. For patients with C. 521 CC and C. 421 AA genotypes, the recommended maximum dose of rosuvastatin is 20 mg per day (see section 4.4).section “Pharmacokinetics”). Concomitant therapy: Rosuvastatin binds to various transport proteins (in particular, OATP1 In 1 and BCRP). Co-use of rosuvastatin with medicinal products (such as cyclosporine, certain human immunodeficiency virus (HIV) protease inhibitors, including ritonavir with atazanavir, lopinavir, and/or tipranavir) that increase the concentration of rosuvastatin in blood plasma due to interaction with transport proteins may increase the risk of myopathy (including rhabdomyolysis). In such cases, the possibility of prescribing alternative therapy or temporarily stopping rosuvastatin should be evaluated. If the use of the above drugs is necessary, the benefit-risk ratio of concomitant therapy with rosuvastatin should be evaluated and the possibility of reducing its dose should be considered.

Overdose

There are no data on overdose of Ekvamer.

Amlodipine

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

Treatment: gastric lavage, use of activated charcoal (especially in the first 2 hours after overdose), maintenance of the cardiovascular system, elevated position of the lower extremities, control of the functions of the cardiovascular and respiratory systems, control of the volume of circulating blood (BCC) and diuresis. To restore vascular tone – the use of vasoconstrictors (in the absence of contraindications to their use); to eliminate the consequences of calcium channel blockade – intravenous use of calcium gluconate. Hemodialysis is ineffective.

Lisinopril

Symptoms: marked decrease  Blood pressure, dry mouth, drowsiness, urinary retention, constipation, restlessness, increased irritability, impaired renal function, water-electrolyte balance, tachycardia, bradycardia, collapse, hyperventilation, dizziness.

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

Rosuvastatin

With simultaneous use 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 overdose, it is recommended to carry out symptomatic treatment and measures aimed at maintaining the functions of vital organs and systems. Monitoring of liver function and CKD activity is necessary. It is unlikely that hemodialysis will be effective.

Special instructions

If you are admitted to a hospital, tell your doctor that you are taking Ekvamer®. If you also forgot to take a capsule of Ekvamer®, please wait and take the next capsule at the usual time. Do not take a double dose to make up for a missed dose. When using the drug Ekvamer®, you should take into account the recommendations for the use of individual components of the drug, described in detail below. Amlodipine requires dental hygiene and dental supervision (to prevent soreness, bleeding, and gum hyperplasia). In elderly patients, the half-life may increase and the clearance of amlodipine may decrease. Dose changes are not required, but more careful monitoring of 5a patients in this category is necessary. The efficacy and safety of amlodipine in hypertensive crisis has not been established. Despite the absence of “withdrawal” syndrome in BMCC, it is advisable to stop treatment with amlodinine by gradually reducing the dose of the drug. When amlodipine was used, patients with non-ischemic CHF of NYIIA functional class III and IV had an increased incidence of pulmonary edema, despite the absence of signs of worsening heart failure. Lisinopril-symptomatic hypotension Most often, a marked decrease in blood pressure occurs with a decrease in BCC caused by diuretic therapy, a decrease in table 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 the absence of it, symptomatic arterial hypotension may develop. It was more often detected in patients with severe heart failure as a result of high-dose diuretics, hyponatremia, or impaired renal function. In such patients, therapy should be initiated under strict medical supervision (with caution, select the dose of lisinopril and diuretics). Similar rules should be followed 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 down and, if necessary, replenish the loss of fluid (intravenous infusion of 0.9% sodium chloride solution). A transient hypotensive reaction is not a contraindication for taking the next dose of lisinopril. When lisinopril is used, some patients with CHF, but with normal or reduced blood pressure, may experience a decrease in blood pressure, which is usually not a reason to stop therapy. If hypotension becomes symptomatic, it is necessary to reduce the dose or discontinue lisinopril therapy. In patients who are at risk of developing symptomatic hypotension (those on a salt-restricted or salt-free diet) with or without hyponatremia, as well as in patients who have received high doses of diuretics, it is necessary to compensate for fluid and salt loss before starting treatment. It is necessary to monitor the antihypertensive effect of the initial dose of lisinopril. Aortic and mitral valve stenosis/hypertrophic obstructive Cardiomyopathiesas with other ACE inhibitors, lisinopril should be administered with caution in patients with mitral valve stenosis and left ventricular outflow tract obstruction (aortic stenosis or hypertrophic obstructive cardiomyopathy). Acute myocardial infarction Standard therapy (thrombolytics, acetylsalicylic acid as an antiplatelet agent, beta-blockers) is contraindicated. Lisinopril can be used in combination with intravenous nitroglycerin or with the use of transdermal nitroglycerin systems. Lisinopril therapy should not be initiated in patients with acute myocardial infarction who are at risk of further serious hemodynamic deterioration after the use of vasodilators (patients with 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 the systolic blood pressure is 120 mm Hg or lower. Maintenance doses of lisinopril should be reduced to 5 mg or temporarily to 2.5 mg if the systolic blood pressure is 100 mm Hg or lower. If hypotension persists (systolic blood pressure is less than 90 mm Hg for more than 1 hour), lisinopril should not be continued. Impaired renal function in patients with CHF, a marked decrease in blood pressure after starting treatment with ACE inhibitors may lead to further deterioration of renal function. Cases of acute renal failure have been reported. In patients with bilateral renal artery stenosis or single kidney artery stenosis treated with ACE inhibitors, an increase in serum urea and creatinine concentrations was observed, which is usually reversible after discontinuation of treatment and is more common in patients with renal insufficiency. Lisinoporil is not used in acute myocardial infarction in patients with severe renal impairment, established when the concentration of serum creatinine exceeds 177 mmol/l, and/or proteinuria exceeds: < 0 mg / day. If renal dysfunction develops during lisinopril therapy (serum creatinine concentration exceeding 265 mmol / l, or doubling the value compared to the indicator before starting treatment), the doctor should evaluate the need for further use of lisinopril. Increased sensitivity/Angioedema angioedema of the face, extremities, lips, tongue, epiglottis, and / or larynx, which may occur during any period of therapy, has rarely been reported in patients treated with an ACE inhibitor, including lisinopril. In this case, lisinopril therapy should be discontinued as soon as possible and the patient should be monitored until symptoms fully regress. In cases where edema occurs only on the face and lips, this condition most often passes without treatment, but antihistamines can be used. Angioedema with laryngeal edema can be fatal.Edema of the tongue, epiglottis or larynx can cause airway obstruction, so it is necessary to immediately conduct appropriate therapy (0.3-0.5 ml of 1:1000 epinephrine solution subcutaneously) and/or take measures to ensure airway patency. It was noted that patients of the black race taking ACE inhibitors developed angioedema more often than in patients of other races. Intestinal angioedema was rarely observed in patients taking ACE inhibitors. These patients complained of abdominal pain (with or without nausea and vomiting); in some cases, there was no previous angioedema of the face, and C-1 esterase activity was within the normal range. Intestinal angioedema was diagnosed by computed tomography of the gastrointestinal tract or ultrasound examination, or by surgical intervention; symptoms disappeared after discontinuation of the ACE inhibitor. When making a differential diagnosis of abdominal pain in patients taking ACE inhibitors, the development of intestinal angioedema should be taken into account. Patients who have a history of angioedema that is not associated with previous treatment with ACE inhibitors may be at increased risk of developing angioedema during treatment with an ACE inhibitor (see also section “Contraindications”), Anaphylactic reactions during desensitization procedures, and patients receiving ACE inhibitors during desensitization (for example, hymenopteran venom), in very rare cases, life-threatening anaphylactic reactions may develop. This can be avoided by temporarily discontinuing the ACE inhibitor before starting each desensitization procedure. Impaired liver function The use of ACE inhibitors can lead to the development of cholestatic jaundice with progression up to fulminant liver necrosis, so it is necessary to stop taking lisinopril with increased activity of “hepatic” transaminases and the appearance of symptoms of cholestasis. Patients undergoing hemodialysis Anaphylactic reactions are also reported in patients undergoing hemodialysis using high-flow membranes (for example, AN69®) and taking ACE inhibitors at the same time. If hemodialysis is necessary, a different type of membrane or a different antihypertensive drug should be used. Cough When using an ACE inhibitor, a “dry”, prolonged cough was noted, which disappeared after stopping treatment with an ACE inhibitor. In the differential diagnosis of cough, it is necessary to take into account n cough caused by the use of an ACE inhibitor. Surgical intervention/General anaesthesia In patients whose condition requires extensive surgery or general anaesthesia with drugs that cause hypotension, lisinopril may block the formation of angiotensin II with compensatory renin release. A pronounced decrease in blood pressure, which is considered a consequence of this mechanism, can be attributed to an increase in the volume of circulating blood. Before surgery (including dental surgery I), the surgeon/anesthesiologist should be informed about the use of an ACE inhibitor. Hyperkalemia Cases of hyperkalemia have been reported. Risk factors for hyperkalemia include renal failure, diabetes mellitus, and concomitant use of potassium-sparing diuretics (spironolactone, eplerenone (a derivative of spironolactone), triamterene, and amiloride), potassium preparations, or salt substitutes containing potassium, especially in patients with impaired renal function. If the simultaneous use of lisinopril and these drugs is necessary, it is recommended to take precautionary measures and regularly monitor the content of potassium in the blood serum. Patients with diabetes mellitus Patients with diabetes mellitus who are taking oral hypoglycemic drugs or receiving insulin, during the first month of treatment with an ACE inhibitor, should carefully monitor the concentration of glucose in the blood plasma. Dual blockade of the RAAS with angiotensin II receptor antagonists (ARA II), ACE inhibitors or ALISKIREN It has been shown that concomitant use of angiotensin II receptor antagonists (ARA II), ACE inhibitors or aliskiren increases the risk of hypotension, hyperkalemia, and impaired renal function (including acute renal failure). For this reason, the combined use of ARA II, ACE inhibitors or aliskiren is not recommended. If the use of this therapy is necessary, it is recommended to monitor a specialist, careful monitoring of renal function, blood pressure and serum electrolytes. ACE inhibitors, ARA II should not be used in patients with diabetic nephropathy. Systemic connective tissue diseasesin patients with severe autoimmune systemic connective tissue diseases (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, so special care is required when determining the dose, despite the fact that there are no differences in the antihypertensive effect of lisinopril in elderly and young patients. Patients receiving rosuvastatin may develop proteinuria. Changes in the amount of protein in the urine (from no or trace amounts to ++ or more) are observed in less than 1% of patients receiving 10-20 mg of rosuvastatin, and in approximately 3% of patients receiving 40 mg of rosuvastatin. A slight change in the amount of protein in the urine was observed when taking a dose of 20 mg. In most cases, proteinuria decreases or disappears during therapy and does not indicate the occurrence of acute or progressive existing kidney disease. From the musculoskeletal systemthe following adverse reactions have been reported with the use of rosuvastatin in all dosages, and especially with doses exceeding 20 mg: myalgia, myopathy, and in rare cases rhabdomyolysis. Determination of creatine phosphokinase activity Determination of CPK activity should not be performed after intense physical exertion or in the presence of other possible causes of increased CPK activity, which may lead to incorrect interpretation of the results. If the initial CPK activity is significantly increased (5 times higher than the upper limit of normal), a second measurement should be performed after 5-7 days. You should not start therapy if a repeated test confirms the initial CPK activity (more than 5 times higher than the upper limit of normal). Caution should be exercised in patients with existing risk factors for myopathy/rhabdomyolysis before starting therapy with rosuvastatin, as well as with other HMG-CoL reductase inhibitors (see section “With caution”). It is necessary to consider the risk / benefit ratio of therapy and conduct clinical monitoring. During therapy, the patient should be informed of the need to immediately inform the doctor about cases of unexpected muscle pain, muscle weakness or spasms, especially in combination with malaise and fever. In such patients, CPK activity should be determined. Therapy should be discontinued if CKD activity is significantly increased (more than 5 times higher than the upper limit of normal) or if muscle symptoms are severe and cause daily discomfort (even if CKD activity is 5 times lower than the upper limit of normal). If symptoms disappear and CPK activity returns to normal, consideration should be given to re-prescribing rosuvastatin or other HMG-CoA reductase inhibitors in lower doses, with careful monitoring of the patient. Routine monitoring of CPK activity in the absence of symptoms is impractical. There were no signs of increased effects on skeletal muscle when taking rosuvastatin and concomitant therapy. However, an increase in myositis and myopathy has been reported in patients taking other HMG-CoA reductase inhibitors (statins) in combination with fibrinic acid derivatives, including emfibrozil, cyclosporine, 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 co-administered with certain HMG-CoA reductase inhibitors. Therefore, concomitant use of rosuvastatin and gemfibrozil is not recommended. The risk/benefit ratio should be carefully weighed when rosuvastatin is co-administered with fibrates or nicotinic acid in lipid-lowering doses (more than 1 g / day of gki). It is contraindicated to take rosuvastatin at a dose of 40 mg together with fibrates (see the section “Interaction with other drugs”). In 2-4 weeks after starting treatment and/or increasing the dose of rosuvastatin, it is necessary to monitor the parameters of lipid metabolism (if necessary, adjust the dose of rosuvastatin). Liver function monitoring It is recommended to determine liver function indicators before the start of therapy and 3 months after the start of therapy. Rosuvastatin should be discontinued or its dose reduced if the activity of “hepatic” transaminases in the blood serum is 3 times higher than the upper limit of normal. In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, treatment of the underlying diseases should be performed before starting treatment with rosuvastatin. Race In the course of studying pharmacokinetic parameters in patients belonging to the Mongolian race, an increase in the systemic concentration of rosuvastatin was noted compared with the indicators of patients of the Caucasian race (see the sections “Dosage and administration” and “Pharmacokinetics”). Co-administration of rosuvastatin with HIV protease inhibitors is not recommended.section “Interaction with other medicinal products”). Interstitial lung diseasewith the use of certain HMG-CoA reductase inhibitors (statins), especially for a long time, isolated cases of interstitial lung disease have been reported. Symptoms of the disease may include shortness of breath, an unproductive cough, and poor overall health (weakness, weight loss, and fever). If interstitial lung disease is suspected, patina therapy should be discontinued. Type 2 diabetes mellitus In patients with fasting glucose concentrations between 5.6 and 6.9 mmol / L, rosuvastatin therapy was associated with an increased risk of developing type 2 diabetes. Excipients Ekvamer ® Lactosapreparation 5 mg + 10 mg + 10 mg and 10 mg + 20 mg + 10 mg contains 48.10 mg of lactose monohydrate in each capsule. Ekvamer® 5 mg + 10 mg + 20 mg and 10 mg + 20 mg + 20 mg contains 96.20 mg of lactose monohydrate in each capsule. Patients with rare hereditary problems such as lactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take Ekvamer. Dye Azorubinpreparation Ekvamer® contains food coloring azorubin. Azorubia can cause the development of allergic reactions. Dye sunny sunset Yellowthe product Ekvamer ® dosage 5 mg + 10 mg + 10 mg and 10 mg + 20 mg + 20 mg contains food dye sunny sunset yellow. Food coloring sunny sunset yellow can cause the development of allergic reactions.

Influence on the ability to drive vehicles and mechanisms

There are no data on the effect of the drug on the ability to drive vehicles and mechanisms. Due to the possible excessive decrease in blood pressure, dizziness, drowsiness and similar side effects, care should be taken when performing potentially dangerous activities that require special attention and quick reactions (driving a car and other vehicles, working with moving mechanisms, working as a dispatcher and operator, etc. ).

Active ingredient

Amlodipine, Lisinopril, Rosuvastatin

Conditions of release from pharmacies

By prescription

Dosage form

Capsules

Purpose

For adults as directed by your doctor

Indications

Hypertension, Atherosclerosis