Ecapress - instructions for use, dose, side effects, contraindications

Similar drugsTo uncover

Dosage form: & nbspmodified release capsules

Composition:

Composition per 1 capsule:

Dosage 5 mg + 1.5 mg + 10 mg

Active substances: Amlodipine besylate - 6,934 mg (equivalent to amlodipine 5 mg), indapamide 1.5 mg, lisinopril dihydrate 10.888 mg (equivalent to lisinopril 10 mg).

Excipients: lactose monohydrate, hypromellose, calcium hydrophosphate dihydrate, mannitol, corn starch, microcrystalline cellulose, croscarmellose sodium, talc, magnesium stearate, colloidal silicon dioxide, Opadrai II white (contains polyvinyl alcohol, titanium dioxide, macrogol-3350, talc), hard gelatin capsule (contains: iron dye oxide yellow, titanium dioxide, water, gelatin).

Dosage of 10 mg + 1.5 mg + 20 mg

Active substances: Amlodipine besylate - 13.868 mg (equivalent to amlodipine 10 mg), indapamide 1.5 mg, lisinopril dihydrate 21.776 mg (equivalent to lisinopril 20 mg).

Excipients: lactose monohydrate, hypromellose, calcium hydrophosphate dihydrate, mannitol, corn starch, microcrystalline cellulose, croscarmellose sodium, talc, magnesium stearate, colloidal silicon dioxide, Opadrai II white (contains polyvinyl alcohol, titanium dioxide, macrogol-3350, talc), hard gelatin capsule (contains: iron oxide dye yellow, iron oxide red dye, titanium dioxide, water, gelatin).

Dosage 5 mg + 1.5 mg + 20 mg

Active substances: Amlodipine besylate - 6,934 mg (equivalent to amlodipine 5 mg), indapamide 1.5 mg, lisinopril dihydrate 21.776 mg (equivalent to lisinopril 20 mg).

Excipients: lactose monohydrate, hypromellose, calcium hydrophosphate dihydrate, mannitol, corn starch, microcrystalline cellulose, croscarmellose sodium, talc, magnesium stearate, colloidal silicon dioxide, Opadrai II white (contains polyvinyl alcohol, titanium dioxide, macrogol-3350, talc), hard gelatin capsule (contains: iron oxide dye yellow, iron oxide red dye, water, gelatin).

Description:

Dosage 5 mg + 1.5 mg + 10 mg

Hard gelatin capsules of yellow color, size No. 1. Contents of capsules - 1 round, biconvex tablet of white color, with engraving "CF4" on one side (contains amlodipine and lisinopril) and 1 oval, biconvex tablet covered with a film shell, white, with the engraving "SRZ" on one side and the risk on the other side (contains indapamide).

Dosage of 10 mg + 1.5 mg + 20 mg

Hard gelatin capsules of light orange color, size No. 1. Contents of capsules - 2 round, biconvex white tablets, engraved "CF4" on one side (contain amlodipine and lisinopril) and 1 oval, biconvex tablet covered with a film shell, white, with the engraving "SRZ" on one side and the risk on the other side (contains indapamide).

Dosage of 5 mg + 1.5 mg + 20 mg

Hard gelatin capsules of dark orange color, size No. 0. Contents of capsules - 2 round, biconvex white tablets, engraved "CF1" on one side (contain amlodipine and lisinopril) and 1 oval, biconvex tablet covered with a film shell, white, with the engraving "SRZ" on one side and the risk on the other side (contains indapamide).

Pharmacotherapeutic group:Hypotensive drug combined (blocker of "slow" calcium channels + diuretic + ACE inhibitor)

ATX: & nbsp

ACE inhibitors in combination with other drugs

Pharmacodynamics:

Equapress is a fixed combination of antihypertensive components of amlodipine, indapamide and lisinopril, which have complementary mechanisms of action that allow controlling blood pressure (BP), and also synergistically have cardioprotective effect.

The combination of amlodipine, indapamide and lisinopril helps to prevent the possible development of side effects that occur with the appointment of individual components of the drug.For example, by expanding arterioles, "slow" calcium channel blockers (BCCs) can cause sodium and fluid retention in the body, leading to the activation of the renin-angiotensin-aldosterone system (RAAS). The angiotensin-converting enzyme (ACE) inhibitor blocks this process and normalizes the body's response to salt load.

ACE inhibitors significantly reduce hypokalemia caused by diuretics.

Amlodipine

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

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

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

In patients with stable angina, a single daily dose increases exercise tolerance, slows the development of angina attacks and segment depression ST at 1 mm, reduces the incidence of angina attacks and the consumption of nitroglycerin and other nitrates.

Has a long-term dose-dependent antihypertensive effect. Antihypertensive action is due to direct vasodilating effect on smooth muscle vessels. With arterial hypertension, a single dose provides a clinically significant decrease in blood pressure over a period of 24 h (in the "lying" and "standing" positions).

Orthostatic hypotension with amlodipine is rare. Amlodipine does not cause a decrease in exercise tolerance, or a fraction of the left ventricular ejection. Reduces the degree of myocardial hypertrophy of the left ventricle. Does not affect the contractility and conductance of the myocardium, does not cause a reflex increase in the heart rate, inhibits platelet aggregation, increases the rate of glomerular filtration, has a weak natriuretic effect.When diabetic nephropathy does not increase the severity of microalbuminuria. 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 and gout. A significant reduction in blood pressure is observed after 6-10 h, the duration of the effect is 24 h.

In patients with diseases of the cardiovascular system (including coronary atherosclerosis with one vessel and up to stenosis of 3 or more arteries, carotid atherosclerosis) who underwent myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA), or in patients with angina pectoris Amlodipine prevents the development of thickening of the intima-media of the carotid arteries, reduces the mortality from myocardial infarction, stroke, PTCA, aorto-coronary shunting; leads to a decrease in 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.

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

Indapamide

Indapamide refers to derivatives of sulfonamide with an indole ring and by pharmacological properties is similar to thiazide diuretics, which inhibit the absorption of sodium ions in the cortical segment of the nephron loop. This increases the release of kidney ions of sodium, chlorine and, to a lesser extent, potassium and magnesium ions, which is accompanied by an increase in diuresis and antihypertensive effect. In clinical studies using indapamide in monotherapy in doses that did not exert a pronounced diuretic effect, a 24-hour antihypertensive effect was demonstrated.

Antihypertensive activity of indapamide is associated with improving the elastic properties of large arteries, reducing arteriolar and general peripheral vascular resistance.

Indapamide reduces hypertrophy of the left ventricle.

Thiazide and thiazide-like diuretics at a certain dose reach a plateau of therapeutic effect, while the incidence of side effects continues to increase with a further increase in the dose of the drug. Therefore, do not increase the dose of the drug, if the recommended dose does not achieve a therapeutic effect.

In short, medium and long-term studies involving patients with hypertension, it was shown that indapamide:

- does not affect the lipid metabolism, including the concentration of triglycerides, cholesterol, low and high density lipoproteins;

- does not affect carbohydrate metabolism, including in patients with diabetes mellitus.

Lisinopril

Lizinopril - an ACE inhibitor, suppresses the transformation of angiotensin I into angiotensin II. Reducing the concentration of angiotensin II leads to a direct decrease in the secretion of aldosterone. Lisinopril inhibits the degradation of bradykinin and increases the synthesis of prostaglandins. Reduces the overall peripheral vascular resistance, blood pressure, preload and pressure in the pulmonary capillaries. In patients with CHF increases the minute volume of blood and increases the resistance of the myocardium to the load.Expands arteries more than veins. Some effects are explained by its effect on the tissue renin-angiotensin system. With prolonged use, myocardial hypertrophy and the walls of arteries of resistive type decrease.

Lizinopril improves the blood supply of the ischemic myocardium.

In patients with CHF, ACE inhibitors increase life expectancy; in patients with a history of myocardial infarction in the absence of clinical manifestations of heart failure lisinopril slows the progression of left ventricular dysfunction.

In patients with CHF lisinopril starts to act within 1 hour after ingestion. The maximum effect is achieved within 6-7 hours; the duration of the effect is 24 hours. In patients with hypertension, the effect occurs within the first days after the start of treatment; stabilization of the effect occurs within 1-2 months of treatment. Cases of marked increase in blood pressure after a sharp discontinuation of the drug are not registered. Lisinopril provides both a reduction in blood pressure and a decrease in albuminuria. In patients with hyperglycemia, the drug contributes to the restoration of the function of the damaged endothelium of the glomeruli. In patients with diabetes mellitus lisinopril does not affect the concentration of glucose in the blood plasma; taking the drug does not increase the incidence of hypoglycemia.

Pharmacokinetics:

Amlodipine

Suction

After oral administration amlodipine is well absorbed from the gastrointestinal tract (GIT). The average absolute bioavailability is 64-80%, Cmah in serum is observed after 6-12 hours. Equilibrium concentrations (Css) are achieved after 7-8 days of therapy. Food intake does not affect the absorption of amlodipine.

Distribution and binding to blood plasma proteins

The average volume of distribution is 21 l / kg body weight, indicating that most of the drug is in the tissues, and the smaller - in the blood. Most of the amlodipine, which is in the blood (97.5%), binds to blood plasma proteins. Amlodipine penetrates the blood-brain barrier.

Metabolism / excretion

Amlodipine undergoes a slow but active metabolism in the liver in the absence of a significant effect of "primary transmission" through the liver. Metabolites do not have significant pharmacological activity. The half-life period (T1 / 2) from the blood plasma varies from 35 to 50 h, which allows taking the medication once a day. T1 / 2 with repeated application - about 45 h.About 60% of the dose taken internally 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). Amlodipine is not removed from the blood plasma during hemodialysis.

Pharmacokinetics in specific patient groups

Elderly patients: in elderly patients (over 65 years of age) amlodipine withdrawal is slowed (T1 / 2 - 65 h) compared with young patients, however this difference has no clinical significance.

Patients with hepatic impairment: lengthening T1 / 2 in patients with liver failure suggests that with prolonged use, cumulation of the drug in the body will be higher (T1 / 2 - up to 60 hours).

Patients with renal insufficiency: renal failure does not have a significant effect on the kinetics of amlodipine.

Indapamide

The active substance is in a special carrier matrix that provides a slow controlled release of indapamide in the gastrointestinal tract.

Suction: released indapamide quickly and completely absorbed in the gastrointestinal tract. The intake of food slightly increases the time of absorption of the drug, without affecting the completeness of absorption. FROMmAch is achieved 12 hours after a single oral intake. With multiple admission, fluctuations in indapamide concentration in the blood plasma are smoothed out. There is an individual variability in the absorption of the drug.

Distribution and binding to blood proteins: about 79% of the drug binds to blood plasma proteins. The half-life is 14-24 hours (on average, 18 hours). The equilibrium concentration is achieved 7 days after the initiation of therapy.

Multiple administration does not lead to cumulation of the drug.

Excretion: indapamide is excreted mainly in the form of inactive metabolites by the kidneys (70% of the administered dose) and through the intestine (22%).

High risk group: the pharmacokinetics of indapamide does not change in patients with renal insufficiency.

Lisinopril

Suction

When ingested in the gastrointestinal tract, about 25% of lisinopril is absorbed. Eating does not affect absorption. Absorption is on average 30%, bioavailability is 29%.

Distribution and binding to blood plasma proteins

The maximum concentration (Cmah) is achieved 6-8 hours after ingestion. The degree of binding to plasma proteins is low. Lisinopril poorly penetrates the blood-brain barrier.

Metabolism

Lizinopril does not undergo biotransformation in the human body.

Excretion

The half-life (T1 / 2) is 12 hours.

Pharmacokinetics in specific patient groups

Patients with chronic heart failure

In patients with CHF, absorption and clearance of lisinopril are reduced. In this category of patients, the absolute bioavailability of lisinopril is reduced by about 16%.

Patients with renal insufficiency

Violation of kidney function leads to an increase AUC (the area under the concentration-time curve) and the half-life of lisinopril, but these changes become clinically significant only when the glomerular filtration rate (GFR) drops below 30 ml / min / 1.73 m². With mild and moderate renal failure (creatinine clearance (CK) from 30 to 80 ml / min), the mean AUC increases by 13%, while in severe renal failure (SC from 5 to 30 ml / min), the mean value increases AUC in 4,5 times.

Patients with hepatic insufficiency

In patients with cirrhosis of the liver, the absorption of lisinopril decreases (by approximately 30%),However, the effect of the drug is increased (by approximately 50%) compared with healthy volunteers due to reduced clearance.

Patients of advanced age (over 65 years)

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

Indications:Arterial hypertension (patients who require combination therapy).

Contraindications:

- Increased sensitivity to amlodipine or other dihydropyridine derivatives.

- Hypersensitivity to lisinopril or other ACE inhibitors.

- Increased sensitivity to indapamide or other sulfonamide derivatives.

- Hypersensitivity to the drug's excipients.

- Severe arterial hypotension (systolic blood pressure below 90 mm Hg).

- Angioedema in the past, including those associated with the use of ACE inhibitors.

- Hereditary or idiopathic angioedema.

- Severe renal insufficiency (creatinine clearance <30 mL / min).

- Hepatic encephalopathy or severe liver dysfunction.

- Hypokalemia.

- Hemodynamically significant obstruction of the outflow tract of the left ventricle (for example, with severe aortic stenosis, hypertrophic obstructive cardiomyopathy), hemodynamically significant mitral stenosis.

- Hemodynamically unstable heart failure after myocardial infarction.

- Shock (including cardiogenic).

- Unstable angina (with the exception of Prinzmetal angina).

- The simultaneous use of the drug Ecupress and preparations containing aliskiren, in patients with diabetes mellitus and / or moderate or severe renal dysfunction (glomerular filtration rate (GFR) of less than 60 ml / min / 1.73 m² surface area of the body).

- Simultaneous use with angiotensin II receptor antagonists (ARA II) in patients with diabetic nephropathy.

- Pregnancy and breastfeeding.

- Age to 18 years (effectiveness and safety not established).

- Hereditary lactose intolerance, galactosemia, glucose-galactose malabsorption syndrome.

Carefully:

Aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, Prinzmetal angina, hypotension,cerebrovascular diseases (including cerebrovascular insufficiency), ischemic heart disease, coronary insufficiency, nonischemic etiology of CHF III-IV class, acute myocardial infarction (as well as within 1 month after myocardial infarction), sick sinus syndrome, severe autoimmune systemic connective tissue disease (including systemic lupus erythematosus, scleroderma), myelosuppression, diabetes mellitus, hyperkalaemia, bilateral renal artery stenosis, renal artery stenosis sole condition after kidney transplantation, renal insufficiency, azotemia, primary aldosteronism, salt diet with restriction conditions associated with a decrease in volume circulatory blood (including vomiting and diarrhea), elderly patients, liver failure.

Weakened patients or patients receiving combination therapy with drugs that extend the interval QT on the ECG (see section "Interaction with other drugs"); simultaneous use with preparations containing aliskiren, or angiotensin II receptor antagonists (ARA II) (increased risk of arterial hypotension,hyperkalemia and renal failure with a double blockade of RAAS); violation of water and electrolyte balance; interval lengthening QT on an electrocardiogram (ECG); hyperuricemia (especially accompanied by gout and urate nephrolithiasis); hyperparathyroidism; in patients of the Negroid race.

Pregnancy and lactation:

Pregnancy

The use of the drug Ekvapress during pregnancy is contraindicated.

Adequately controlled clinical studies of the use of the drug Ekvapress during pregnancy were not conducted. When you are pregnant, you must immediately stop taking Ecoverress. Pregnant women planning to go to another antihypertensive drug with an established safety profile during pregnancy.

Lisinopril

The intake of ACE inhibitors by pregnant women in 2-3 trimesters can lead to death of the fetus or newborn. To detect a possible significant decrease in blood pressure, oliguria, and hyperkalemia, careful monitoring of the condition of newborns and infants whose mothers have been taken with ACE inhibitors in the prenatal period is shown.It is possible to develop malnutrition, as well as hypoplasia of the facial bones, deformation of the bones of the face and skull, lung hypoplasia and impaired renal development in newborns. Women of childbearing age should use reliable methods of contraception. Lisinopril penetrates the placental barrier. Lisinopril contraindicated in pregnancy.

Amlodipine

The safety of amlodipine in pregnancy is not established, so its use during pregnancy is possible only if the benefit to the mother exceeds the risk for the newborn.

Indapamide

As a rule, diuretics are contraindicated during pregnancy. It is forbidden to use these drugs to reduce the physiological edema during pregnancy. Diuretics can lead to fetoplacental insufficiency and intrauterine growth disorders.

Breastfeeding period

The use of the drug Ecupress is contraindicated during breastfeeding.

Lisinopril

There are no data on the penetration of lisinopril into breast milk. During treatment with lisinopril, breastfeeding should be stopped.

Amlodipine

It is not known whether the amlodipine in breast milk.It is known that other BCCC derivatives of dihydropyridine penetrate into breast milk.

Indapamide

Not recommended for lactating mothers (indapamide penetrates into breast milk).

Dosing and Administration:

Mode of application

The drug Ecapress is taken internally, regardless of food intake.

Doses

Combined drugs with fixed doses are not recommended for initial therapy. The drug Ecapress is assigned to adult patients who have adequate control of blood pressure on the background of taking lisinopril, amlodipine and indapamide, which the patient takes simultaneously in the same doses as in the combined drug: amlodipine 5 mg, indapamide 1.5 mg, lisinopril 10 mg (Equapress 5 mg + 1.5 mg + 10 mg), amlodipine 10 mg, indapamide 1.5 mg, lisinopril 20 mg (Equapress 10 mg + 1.5 mg + 20 mg), amlodipine 5 mg, indapamide 1.5 mg, lisinopril 20 mg (Equapress 5 mg + 1.5 mg + 20 mg).

The recommended dose is 1 capsule per day, preferably in the morning, at the same time each day. The maximum daily dose is 1 capsule.

With the development of symptomatic arterial hypotension at the beginning of treatment with the drug Ekvapress patient should lie on his back, stop taking the drug and see a doctor.Transient arterial hypotension usually does not require withdrawal of the drug, but the need to reduce the dose should be assessed.

If it is necessary to select a dose, you should use medicines amlodipine, indapamide and lisinopril apart.

Padmission administration

If you forget to take the capsule of the drug Ecupress, then take the next dose at the usual time. Do not take two capsules at the same time to compensate for the missed dose.

Special patient groups

Patients with renal insufficiency

On the background of therapy with the drug Ekvapress, control of the kidney function, as well as the content of potassium and sodium in the blood serum, is necessary. If the kidney function worsens, you should abolish the drug Ecupress and replace it with individually selected therapy from individual components.

Patients with hepatic insufficiency

In patients with impaired hepatic function, amlodipine excretion may be slowed. For such cases, there are no precise recommendations, therefore, the drug Ecupress should be used with caution in these patients.

Children and adolescents (<18 years old)

The safety and effectiveness of the drug Ecupress in children and adolescents is not established.

Elderly patients (> 65 years)

This drug should be used with caution in elderly patients.

It is necessary to monitor the concentration of creatinine in the blood plasma in accordance with age, body weight and sex.

Changes in the profile of efficacy and safety of amlodipine or lisinopril, dependent on age, were not found in clinical studies.

Side effects:

The most frequent adverse reactions reported in the treatment with amlodipine, indapamide and lisinopril as monotherapy were: dizziness, headache, drowsiness, visual impairment, tinnitus, palpitation, blood flushes to the skin of the face, lowering blood pressure (and effects associated with hypotension), cough, shortness of breath, gastrointestinal disorders (abdominal pain, constipation, diarrhea, nausea, dyspepsia, vomiting), maculopapular rash, muscle spasms, swelling in the ankles, asthenia, swelling and fatigue.

The following undesirable drug reactions (HLR) were recorded during the separate use of amlodipine-1, indapamide-2 and lisinopril-3.

The frequency is defined as follows:

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

Often - 1/100 of prescriptions (≥1% and <10%).

Not infrequently - 1/1000 appointments (≥0.1% and <1%).

Rarely - 1/10000 appointments (≥0.01% and <0.1%).

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

The frequency is unknown (the frequency can not be estimated from the available data).

Within each frequency group, undesirable reactions are presented in order of decreasing importance.

Violations of the blood and lymphatic system

decrease in hemoglobin^{3 (rarely)}, a decrease in hematocrit^{3 (rarely)}, oppression of bone marrow hematopoiesis^{3 (very rarely)}, leukopenia^{1,2,3 (very rarely)}, thrombocytopenia^{1,2,3 (very rarely)}, agranulocytosis^{2.3 (very rarely)}, aplastic anemia^{2 (very rarely)}, hemolytic anemia^{2.3 (very rarely}), neutropenia^{3 (very rarely)}, anemia^{3 (very rarely)}, lymphadenopathy^{3 (very rarely)}.

Immune system disorders

allergic reactions^{1 (very rarely)}, autoimmune disorders^{3 (very rarely)}.

Disorders from the endocrine system

syndrome of inadequate secretion of antidiuretic hormone^{3 (rarely)}.

Disorders from the metabolism and nutrition

hyperglycemia^{1 (very rarely)}, hypoglycaemia^{3 (very rarely)}, hypercalcemia^{2 (very rarely)}, decrease in potassium content and development of hypokalemia^{2 (frequency is unknown)}, especially significant for patients at risk (see "Special instructions"); hyponatremia^{2 (frequency is unknown)} (see "Special instructions").

Disorders of the psyche

mood lability^{1.3 (infrequently)}, sleep disorders^{3 (infrequently)}, hallucinations^{3 (infrequently)}, insomnia^{1 (infrequently)}, anxiety^{1 (infrequently)}, depression^{1 (infrequently), 3 (frequency} ^unknown), confusion^{1.3 (rarely)}.

Disturbances from the nervous system

dizziness^{1.3 (often)}, headache^{1.3 (often), 2(rarely)}, drowsiness^{1 (often)}, increased fatigue^{2 (rarely)}, vertigo^{2 (rarely), 3 (infrequently}), paresthesia^{2 (rarely), 1.3}(^infrequently), dysgeusia^{1.3 (infrequently)}, faint ^{1 (infrequently), 2.3 (frequency unknown)},tremor^{1 (infrequently)}, hypoesthesia^{1 (infrequently)}, parosmia smell)^{3 (rarely)}, hypertonic muscle^{1 (very} ^rarely), peripheral neuropathy^{1 (very} ^rarely),extrapyramidal disorders^{1 (frequency unknown)}.

Disturbances on the part of the organ of sight

impaired vision (including diplopia) ^{1 (often), 2 (frequency is unknown)}, myopia^{2 (frequency is unknown)}, blurred vision^{2 (frequency is unknown)}.

Hearing and balance disorders

noise in ears^{1 (infrequently)}.

Heart Disease

heart palpitations^{1 (often), 3 (infrequently)}, myocardial infarction^{3 (infrequently), 1 (very rarely)}, tachycardia^{3 (infrequently)}, ventricular tachycardia ^{1 (infrequently)}, arrhythmia^{1 (infrequently), 2 (very rarely)}, polymorphic ventricular tachycardia of the "pirouette" type (potentially fatal)^{2 (frequency is unknown)}, bradycardia^{1 (infrequently)}, atrial fibrillation ^{1 (infrequently)}.

Vascular disorders

Orthostatic hypotension and related symptoms^{3 (often)}, "tides" of blood to the skin of the face^{1 (often)}, acute disturbance of cerebral circulation^{3 (infrequently)} (due to a marked decrease in blood pressure in groups of patients at increased risk), Raynaud's syndrome^{3 (infrequently)}, vasculitis^{1 (very rarely)}, hypotension ^{1 (infrequently)}, marked decrease in blood pressure^{2 (very rarely)}.

Disturbances from the respiratory system, chest and mediastinal organs

dyspnea^{1 (often)}, coughing^{1 (infrequently),} ^{3 (often)}, rhinitis^{1.3 (infrequently)}, bronchospasm^{3 (very rarely)}, allergic alveolitis^{3 (very rarely)}, eosinophilic pneumonia^{3 (very rarely)}, sinusitis^{3 (very rarely)}.

Disorders from the gastrointestinal tract

abdominal pain^{1 (often),} ³(^infrequently), nausea^{1 (often), 2 (rarely),} ^{3 (infrequently)},dyspepsia^{1 (often), 3 (infrequently)},change in the rhythm of defecation^{1 (often)}, diarrhea^{1.3 (often)}, constipation^{1 (often), 2 (rare)}, vomiting^{1,2 (infrequently), 3 (often)}, dry mouth^{1 (infrequently), 2.3 (rarely)}, pancreatitis^{1,2,3 (very rarely)},gastritis¹ ^(rarely), interstitial angioedema _FROMek^{3 (very rarely)}, gingival hyperplasia^{1 (very rarely)}.

Disturbances from the liver and bile ducts

hepatitis^{1 (very rarely), 2}(^frequency ^unknown), hepatitis (including hepatic-cellular or cholestatic)^{3 (very rarely)}, jaundice^{1.3 (very rarely)}, liver failure^{3 (very rarely)}, the development of hepatic encephalopathy in the case of liver failure^{2 (frequency unknown}), a dysfunction of the liver^{2 (very rarely)}, increased activity of "liver" enzymes *^{1 (very rarely)}.

(* - mainly in association with cholestasis)

Disturbances from the skin and subcutaneous tissues

alopecia ^{1 (infrequently), 3 (rarely)}, hypersensitivity reactions^{2 (often)}, maculopapular rash^{2 (often)}, exanthema^{1 (infrequently)}, purple ^{1,2 (infrequently)}, depigmentation of the skin^{1 (infrequently)}, hyperhidrosis^{1 (infrequently), 3 (very rarely)}, itchy skin^{1.3 (infrequently)},rash^{1.3 (infrequently)},hives^{1 (infrequently), 2 (very rare), 3 (rarely)}, _Psoriasis^{3 (rarely)}, erythema multiforme^{1.3 (very rarely)}, angioedema^{1,2 (very rare), 3 (rare)}, exfoliative dermatitis^{1 (very rarely)}, toxic epidermal necrolysis^{2.3 (very rarely)}, Stevens-Johnson syndrome^{1,2,3 (very rarely)}, angioedema^{1 (very rarely)}, photosensitivity^{1 (very rarely),} ^{2 (frequency is unknown)}, vulgar pemphigus^{3 (very rarely)}, benign skin lymphadenosis *^{3 (very rarely)}, exacerbation of already existing acute systemic lupus erythematosus^{2 (frequency is unknown)}, hypersensitivity / angioedema, swelling of the face, hands and feet, lips, tongue, glottis and / or larynx^{3 (rarely)}.

(* - reported on a symptom complex that may include one or more of the following symptoms: fever, vasculitis, myalgia, arthralgia / arthritis, positive response to antinuclear antibodies (ANA), increased erythrocyte sedimentation rate (ESR), eosinophilia and leukocytosis, skin rash , photosensitization or other changes from the skin).

Disturbances from musculoskeletal and connective tissue

muscle cramps^{1 (often)}, swelling in the ankle^{1 (often)}, arthralgia^{1 (infrequently)}, myalgia^{1 (infrequently)}, backache^{1 (infrequently)}.

Disorders from the kidneys and urinary tract

impaired renal function^{3 (often)}, upset urination^{1 (infrequently)}, nocturia^{1 (infrequently)}, frequent urination^{1 (infrequently)}, acute renal failure^{1 (rarely)}, kidney failure^{2 (very} ^rarely), uremia^{3 (rarely)}, oliguria^{3 (very rarely)}, anuria^{3 (very rarely)}.

Violations of the genitals and mammary gland

gynecomastia^{1 (infrequently), 3 (rarely)}, impotence^{1.3 (infrequently).}

General disorders and disorders at the site of administration

edema^{1 (very often)}, increased fatigue ^{1 (often), 3 (infrequently)}, asthenia ^{1 (often), 3 (infrequently)}, chest pain^{1 (infrequently)}, pain^{1 (infrequently)}, malaise^{1 (infrequently)}.

Impact on laboratory and instrumental research results:

increase in the concentration of creatinine and urea^{3 (infrequently)}, hyperkalemia^{3 (infrequently)}, hyperbilirubinemia^{3 (rarely)}, increased activity of "hepatic" enzymes^{2 (frequency}unknown), 3 (infrequently), hyponatremia^{3 (rarely)}, lengthening the interval QT on ECG^{2 (frequency}^unknown) (cm. "Interaction with other drugs" and "Special instructions"), an increase in the concentration of uric acid^{2 (frequency unknown}) (see "Special instructions"), an increase in the concentration of glucose in the blood^{2 (frequency is unknown)} (see "Special instructions"), decrease or increase in body weight^{1 (infrequently)}.

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

Overdose:

Overdose of amlodipine

Symptoms: a significant reduction in blood pressure with the possible development of a reflex tachycardia and excessive peripheral vasodilation (there is a risk of developing significant and persistent hypotension, with the development of shock and death).

Treatment: gastric lavage, the appointment of activated charcoal (especially during the first 2 hours after an overdose), giving the patient a horizontal position with raised lower limbs, active support of the function of the cardiovascular system, monitoring the parameters of the function of the heart and lungs, monitoring the volume of circulating blood and diuresis. In the absence of contraindications for the restoration of vascular tone and blood pressure, it may be advisable to appoint vasoconstrictors. Intravenous injections of calcium gluconate may contribute to cessation of the effects of calcium channel blockade. As amlodipine is largely associated with serum proteins, hemodialysis is ineffective in the treatment of an overdose of amlodipine.

Overdose of indapamide

There were no toxic effects of indapamide in overdose even at very high doses (up to 40 mg, ie 27 times higher than the therapeutic dose).

Signs of acute poisoning with indapamide are primarily associated with a violation of the water-electrolyte balance (hyponatremia, hypokalemia). Clinical symptoms of overdose may include nausea, vomiting, decreased blood pressure, convulsions, dizziness, drowsiness, confusion, polyuria, or oliguria leading to anuria (due to hypovolemia).

Emergency measures include removing the drug from the body, washing the stomach and / or taking activated charcoal with the restoration of the water electrolyte balance.

Overdose of lisinopril

Symptoms: significant reduction in blood pressure, dry mouth, drowsiness, delay urination, constipation, anxiety, increased irritability.

Treatment: symptomatic therapy, intravenous injection of 0.9% sodium chloride solution and, if possible, vasopressors, blood pressure control, water-electrolyte balance control. It is possible to conduct hemodialysis (see "Special instructions: Patients, who are on hemodialysis ").

Interaction:

Amlodipine

Contraindicated drug combinations

Dantrolene (intravenous administration)

In laboratory animals, cases of ventricular fibrillation with a lethal outcome and collapse were observed with verapamil and intravenous dantrolene. accompanied by hyperkalemia. Due to the risk of developing hyperkalemia, simultaneous use of the drug Ecupress, containing amlodipine, a blocker of "slow" calcium channels, in patients prone to malignant hyperthermia, as well as in the treatment of malignant hyperthermia.

Unrecommended combinations of drugs

Grapefruit juice

Taking amlodipine with grapefruit or grapefruit juice is not recommended, as in some patients the bioavailability of amlodipine may increase, which leads to an increase in the effects of lowering blood pressure.

Combinations of medicines, requiring special care when applying

Inductors of isoenzyme CYP3A4

Data on the influence of inducers of isoenzyme CYP3A4 on the pharmacokinetics of amlodipine are absent. Simultaneous reception of isoenzyme inducers CYP3A4 (for example, rifampicin, St. John's wort products) and amlodipine may lead to a decrease in plasma concentrations of amlodipine. Caution should be exercised while using the drug Ecupress and isoenzyme inducers CYP3A4.

Inhibitor inhibitors CYP3A4

Simultaneous reception of amlodipine and strong or moderate inhibitors CYP3A4 (protease inhibitors, for example, ritonavir, antifungal agents of the azole group, macrolides, for example, erythromycin or clarithromycin, verapamil or diltiazem) can lead to a significant increase in the concentration of amlodipine. Clinical manifestations of these pharmacokinetic abnormalities may be more pronounced in elderly patients. In this regard, it may be necessary to monitor the clinical status and dose adjustment of the drug Ecupress.

Combinations of medicines, requiring caution when applying

Simvastatin

Multiple admission of amlodipine at a dose of 10 mg in combination with simvastatin at a dose of 80 mg led to an increase in the exposure of simvastatin by 77% compared with simvastatin monotherapy.Thus, patients receiving amlodipine, should be taken simvastatin in a daily dose of not more than 20 mg.

Calcium preparations

Can reduce the effect of BCCI.

Lithium preparations

When BCCC is combined with lithium preparations (there is no data for amlodipine), the manifestation of their neurotoxicity may be enhanced (nausea, vomiting, diarrhea, ataxia, tremor, or tinnitus).

Baclofen

Increased antihypertensive effect. It is necessary to monitor blood pressure and kidney function, if necessary - adjust the dose of amlodipine.

Amifostine

It is possible to increase the antihypertensive effect of amlodipine.

Glucocorticosteroids

Reduction of antihypertensive action (fluid retention and sodium ions due to the action of corticosteroids).

Tricyclic antidepressants of antipsychotics, isoflurane

There is an increased risk of orthostatic hypotension and increased antihypertensive effect (additive effect).

Tacrolimus

With simultaneous use with amlodipine, there is a risk of increasing tacrolimus concentration in the blood plasma. In order to avoid the toxicity of tacrolimus when used simultaneously with amlodipine,It is necessary to monitor the concentration of tacrolimus in the blood plasma of patients and adjust the dose of tacrolimus, if necessary.

Tasononmin

With simultaneous application amlodipine can increase the system exposure tasononemine in the blood plasma. In such cases, regular monitoring of the tasononemine in the blood and a dose adjustment if necessary.

Other interactions with amlodipine

For the treatment of hypertension amlodipine can be safely applied with thiazide diuretics, alpha-adrenoblockers, beta-blockers and ACE inhibitors. In patients with stable angina, simultaneous use of amlodipine with other antianginal drugs, such as nitrates long and short action, beta-blockers.

Probably, an increase in the anti-anginal and antihypertensive effect of BCCK with simultaneous use with thiazide and loop diuretics, ACE inhibitors, beta-adrenoblockers and nitrates, as well as an increase in their antihypertensive effect when administered with alpha-1-adrenergic blockers and neuroleptics.

Amlodipine does not cause a negative inotropic effect.Nevertheless, some BCCI may increase the severity of the negative inotropic effect of antiarrhythmic drugs that cause lengthening of the interval QT (eg, amiodarone and quinidine).

Unlike other BCCI, there was no significant interaction of amlodipine (3rd generation BCCC) and NSAIDs, including indomethacin.

Securely assign amlodipine from oral hypoglycemic drugs. One-time reception sildenafil in a dose of 100 mg in patients with essential hypertension did not affect the pharmacokinetics of amlodipine. A joint multiple dose of amlodipine at a dose of 10 mg and atorvastatin in a dose of 80 mg led to an insignificant change in the pharmacokinetic parameters of atorvastatin in a state of equilibrium concentration.

Ethanol (drinks containing alcohol): amlodipine does not have a significant effect on the pharmacokinetics of ethanol with a single and repeated application in a dose of 10 mg. Interaction Studies cyclosporine and amlodipine in healthy volunteers and in special groups of patients were not performed, except for patients after kidney transplantation.Various studies of the interaction of amlodipine with cyclosporine in patients after kidney transplantation show that the use of this combination can either not lead to any effect or increase the minimum concentration of cyclosporin to varying degrees to 40%. It is necessary to monitor the concentration of cyclosporine in patients after kidney transplantation.

With the simultaneous use of amlodipine and digoxin the renal clearance and serum digoxin concentration do not change.

With simultaneous application warfarin with amlodipine prothrombin time does not change.

When used simultaneously with cimetidine the pharmacokinetics of amlodipine does not change.

Amlodipine does not affect the degree of binding digoxin, phenytoin, warfarin and indomethacin with blood plasma proteins in vitro.

Aluminum and magnesium-containing antacids: a single administration of such antacids together with amlodipine does not significantly affect the pharmacokinetics of amlodipine.

Indapamide

Contraindicated combinations of medicines

Lithium preparations

With the simultaneous use of indapamide and lithium preparations,as well as when observing a salt-free diet, there may be an increase in the concentration of lithium in the blood plasma due to a decrease in its excretion, accompanied by the appearance of signs of an overdose. If necessary, diuretic drugs can be used in combination with lithium preparations, while carefully monitoring the lithium content in blood plasma and appropriately select the dose of the drug.

Combinations of drugs that require extreme caution when used

Drugs that can cause polymorphic ventricular tachycardia such as "pirouette"

- Antiarrhythmic drugs IA class (quinidine, hydroquinidine, disopyramide).

- Antiarrhythmic drugs of III class (amiodarone, sotalol, dofetilide, ibutilide).

- Some antipsychotics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol).

- Others: beprideil, cisapride, difemanyl, erythromycin (intravenously), halofantrine, misolastine, pentamidine, sparfloxacin, moxifloxacin, astemizole, wincamine (intravenously).

Increased risk of ventricular arrhythmias, especially polymorphic ventricular tachycardia such as pirouette (risk factor - hypokalemia).

It is necessary to determine the concentration of potassium in the blood plasma and, if necessary, adjust it before the start of combination therapy with indapamide and the above drugs. It is necessary to monitor the clinical state of the patient, control the level of electrolytes of blood plasma, ECG parameters.

Patients with hypokalemia should use drugs that do not cause polymorphic ventricular tachycardia such as pirouette.

Non-steroidal anti-inflammatory drugs (for systemic use), including selective inhibitors of COX-2, high doses of salicylic acid (≥3 g / day)

It is possible to reduce the antihypertensive effect of indapamide.

There is a risk of developing acute kidney failure due to reduced glomerular filtration. Patients need to compensate for fluid loss and at the beginning of treatment carefully monitor kidney function.

ACE Inhibitors

The appointment of ACE inhibitors to patients with a initially reduced concentration of sodium ions in the blood (especially patients with renal stenosisarteries) is accompanied by a risk of sudden arterial hypotension and / or acute renal failure. Patients with hypertension and possibly decreased due to the intake of diuretics with the content of sodium ions in the blood plasma it is necessary:

- 3 days before the start of treatment with an ACE inhibitor stop taking a diuretic. In the future, if necessary, the intake of a non-potassium-sparing diuretic can be resumed;

- or initiate therapy with an ACE inhibitor from low doses, followed by a gradual increase in dose if necessary.

When chronic heart failure treatment with ACE inhibitors should be prescribed at the lowest dose with a possible preliminary reduction in the dose of diuretics. In all cases in the first weeks of taking ACE inhibitors in patients, it is necessary to monitor the kidney function (creatinine content in the blood plasma).

Other drugs that can cause hypokalemia: amphotericin B (with intravenous administration), gluco- and mineralocorticosteroids (with systemic application), tetrakozaktid, laxatives, stimulating motility intestines

Increased risk of hypokalemia (additive effect).

It is necessary to constantly monitor the concentration of potassium in the blood plasma, if necessary - its correction. Particular attention should be given to patients who simultaneously receive cardiac glycosides. It is recommended to use laxatives that do not stimulate intestinal motility.

Baclofen

There is an increase in antihypertensive effect.

Patients need to compensate for fluid loss and at the beginning of treatment carefully monitor kidney function.

Cardiac glycosides

Hypokalemia increases the toxic effect of cardiac glycosides.

With simultaneous use of indapamide and cardiac glycosides, it is necessary to monitor the potassium content in the blood plasma, the ECG parameters and, if necessary, adjust the therapy.

Combinations of medicines that require caution when used

Potassium-sparing diuretics (amiloride, spironolactone, triamterene, eplerenone) Combination therapy with indapamide and potassium-sparing diuretics is advisable in some patients, but the possibility of hypokalemia or hyperkalemia (especially in patients with diabetes mellitus or in patients with renal insufficiency) is not ruled out.

It is necessary to monitor the concentration of potassium in the blood plasma, the parameters of the ECG and, if necessary, adjust the therapy.

Metformin

Functional renal failure, which can occur against the background of diuretics, especially loop, with the simultaneous appointment of metformin increases the risk of lactic acidosis.

Do not use metformin, if the level of creatinine in the blood plasma exceeds 15 mg / L (135 μmol / L) in men and 12 mg / L (110 μmol / L) in women.

Iodine-Containing Contrasting Products

With dehydration caused by diuretics, the risk of acute renal failure increases, especially when high doses of iodine-containing contrast media are used.

Before using iodine-containing contrast agents, patients must compensate for fluid loss.

Tricyclic antidepressants, antipsychotics (antipsychotics)

Preparations of these classes increase the antihypertensive effect of indapamide and increase the risk of orthostatic hypotension (additive effect).

Salts of calcium

With simultaneous use, the risk of hypercalcemia is increased by reducing the excretion of calcium ions by the kidneys.

Cyclosporin, tacrolimus

It is possible to increase the creatinine content in the blood plasma without changing the concentration of circulating cyclosporine, even with a normal volume of circulating blood and sodium content in the blood plasma.

Glucocorticosteroid preparations, tetrakozaktid (with systemic application)

Reduction of antihypertensive action (fluid retention and sodium ions caused by corticosteroids).

Lisinopril

Contraindicated combinations of medicines

Aliskiren

Simultaneous administration of ACE inhibitors with aliskiren and aliskiren-containing preparations in patients with diabetes mellitus and / or moderate or severe renal dysfunction (GFR less than 60 mL / min / 1.73 m² surface area of the body) contraindicated.

The use of ACE inhibitors with angiotensin II receptor antagonists contraindicated patients with diabetic nephropathy.

Unrecommended combinations of drugs

Angiotensin II receptor antagonists (APA II)

In the literature it was reported that in patients with established atherosclerotic disease, chronic heart failure or diabetes mellitus with damage to target organs,simultaneous therapy with an ACE inhibitor and ARA II is associated with a higher incidence of arterial hypotension, syncope, hyperkalemia, and impaired renal function (including acute renal failure) compared with the use of only one drug that affects RAAS. Double blockade (for example, with the combination of an ACE inhibitor with APA II) should be limited to individual cases with careful monitoring of kidney function, potassium and blood pressure.

Potassium preparations, potassium-sparing diuretics (spironolactone, triamterene, amiloride. eplerenone) or potassium-containing salt substitutes

Perhaps the development of hyperkalemia (with a possible fatal outcome), especially if the kidney function is impaired (additional effects associated with hyperkalemia). ACE inhibitors should not be used concomitantly with substances that increase the level of potassium in the blood plasma, except for cases of hypokalemia. The combination of lisinopril and the above remedies is not recommended. If, however, simultaneous application is shown, they should be used, observing safety precautions and regularly monitoring the potassium content in serum.

Lithium preparations

With simultaneous use of lithium drugs and ACE inhibitors, a reversible increase in serum lithium concentration and related toxic effects can be noted. The simultaneous use of lisinopril and lithium preparations is not recommended. If this therapy is necessary, a regular monitoring of the concentration of lithium in serum should be carried out.

Combinations of medicines, requiring special care when applying

Insulin and oral hypoglycemic agents

Epidemiological studies have shown that the combined use of ACE inhibitors and hypoglycemic agents (insulins, hypoglycemic agents for oral administration) can enhance their hypoglycemic action until the development of hypoglycemia. This effect is most likely to be observed during the first weeks of simultaneous therapy, as well as in patients with impaired renal function. Baclofen

Strengthens the antihypertensive effect of ACE inhibitors. You should carefully monitor the level of blood pressure and, if necessary, adjust the dose of antihypertensive drugs.

Diuretics

In patients taking diuretics, especially those taking out fluid and / or salts, at the beginning of therapy with an ACE inhibitor, a significant reduction in blood pressure can be observed. The risk of developing antihypertensive effects can be reduced by eliminating the diuretic, replenishing the loss of fluid or salts before starting therapy with ACE inhibitors. With arterial hypertension in patients with previous diuretic therapy, which could lead to excessive excretion of fluid and / or salts, diuretics should be discontinued before the use of the drug Ecupress.

The function of the kidneys (creatinine concentration) should be monitored in the first weeks of using the drug Ecupress.

Non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid at a dose of ³3 g / day

Simultaneous use of ACE inhibitors with NSAIDs (acetylsalicylic acid in a dose that has an anti-inflammatory effect, cyclooxygenase-2 (COX-2) inhibitors and nonselective NSAIDs) can lead to a decrease in the antihypertensive effect of ACE inhibitors. Simultaneous use of ACE inhibitors and NSAIDs can lead to impaired renal function,including the development of acute renal failure and an increase in potassium in the blood serum, especially in patients with reduced renal function. Care should be taken when prescribing this combination, especially in elderly patients. Patients should compensate for the loss of fluids and carefully monitor renal function at the beginning of treatment and during treatment.

Estramustine, inhibitors mTOR (sirolimus, everolimus, tessirolimus), neutral endopeptidase inhibitors (omapatrilate, ilepatril, daglutril, sacubitryl) Simultaneous use of estramustine with ACE inhibitors is accompanied by an increased risk of angioedema.

DPP-4 inhibitors (glyptins)

Linagliptin, saxagliptin, sitagliptin, vildagliptin - when combined with ACE inhibitors, the risk of angioedema due to suppression of dipeptidyl peptidase-4 (DPP-4) by glyptin is increased.

Racecadotril (an enkephalinase inhibitor used to treat acute diarrhea)

With simultaneous use with ACE inhibitors, the risk of developing angioedema may increase.

Combinations of medicines that require caution when used

Other antihypertensives (for example,, beta-adrenoblockers, blockers of "slow" calcium channels, diuretics) and vasodilators

It is possible to increase the antihypertensive effect of the drug. Caution should be exercised when concomitant administration with nitroglycerin, other nitrates or other vasodilators, as this may further reduce blood pressure.

Antacids and cholestyramine

Simultaneous use with antacids and cholestyramine leads to suppression of gastrointestinal absorption.

Tricyclic antidepressants, antipsychotics, aids for general anesthesia, barbiturates, phenothiazine, ethanol

With joint admission, it is possible to intensify the action of lisinopril.

FROMimpatomimetics

Sympathomimetics can weaken the antihypertensive effect of ACE inhibitors.

Muscle relaxants

Simultaneous use of muscle relaxants with ACE inhibitors can lead to a marked decrease in blood pressure.

Preparations of gold

With the use of ACE inhibitors, including lisinopril, patients receiving intravenously a preparation of gold (sodium aurotomy malate), rare cases of nitrite reaction (a symptom complex including facial flushing, nausea, vomiting and arterial hypotension) have been described.

Co-trimoxazole (sulfamethoxazole and trimethoprim)

Increased risk of hyperkalemia.

Selective serotonin reuptake inhibitors (SSRIs: escitalopram, paroxetine, fluoxetine, sertraline)

With simultaneous application with SSRIs, it is possible to develop pronounced hyponatremia.

Allopurinol, procainamide, cytostatics (5-fluorouracil, vincristine, docetaxel)

Possible development of leukopenia.

Tissue activators of plasminogen (alteplase, reteplase, tenecteplase)

Increased risk of angioedema and simultaneous use with ACE inhibitors.

Special instructions:

In case of hospitalization, tell your doctor that you are taking Ecupress.

When applying the drug, Ecupress should take into account the specific instructions for individual components of the drug.

Associated with amlodipine

It is necessary to maintain hygiene of the teeth and supervision by the dentist (to prevent soreness, bleeding and gingival hyperplasia).

In elderly patients, T1 / 2 can increase and amlodipine clearance decreases. Dose changes are not required, but more careful monitoring of patients of this category is necessary.

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

In studies in vitro shown, that amlodipine does not affect the degree of binding of digoxin, phenytoin, warfarin or indomethacin to human plasma proteins.

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

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

Impact on fertility

In some patients receiving calcium channel blockers, reversible biochemical changes in the sperm head were found, which may be clinically significant for in vitro fertilization (IVF).

However, at present there is insufficient clinical data on the potential impact of amlodipine on fertility.In a preclinical study, undesirable effects on fertility in males were identified.

Indapamide-related

Impaired liver function

With the appointment of thiazide and thiazide-like diuretics, patients with impaired hepatic function may develop hepatic encephalopathy, especially if there is electrolyte imbalance. In this case, it is necessary to stop the use of diuretics.

Photosensitivity

With the use of thiazide and thiazide-like diuretics, there have been cases of the development of photosensitization (see the "Side effect" section). With the development of photosensitization, the withdrawal of these drugs is indicated. If necessary, continue treatment is recommended to protect the skin from sunlight or artificial UV radiation.

Water-electrolyte balance

The content of sodium in the blood plasma

Before the start of treatment should determine the content of sodium in the blood plasma and regularly monitor this figure. All diuretics can cause hyponatraemia, which can lead to extremely severe consequences. It is necessary to constantly monitor the sodium content in the blood plasma, since at first its decrease may not have clinical manifestations.Especially careful control of the sodium content should be performed in patients with cirrhosis of the liver and in the elderly (see the sections "Side effect" and "Overdose").

All diuretics can cause hyponatremia, which sometimes leads to extremely serious consequences. Hyponatremia and hypovolemia can lead to dehydration and orthostatic hypotension. The concomitant decrease in chloride ions can lead to secondary compensatory metabolic alkalosis: the frequency and severity of this effect are negligible.

The content of potassium in blood plasma

Against the background of therapy with thiazide and thiazide-like diuretics, a sharp decrease in the potassium content in the blood plasma is possible, as well as the development of hypokalemia. It is necessary to prevent the risk of development of hypokalemia (<3.4 mmol / L) in the following patient groups: elderly, weakened patients and / or receiving concomitant medication, patients with cirrhosis, peripheral edema and ascites, coronary heart disease, heart failure. In such patients, hypokalemia increases the toxic effects of cardiac glycosides and increases the risk of arrhythmias.In addition, the high-risk group includes patients with an elongated interval QT, it does not matter whether this increase is due to innate causes or effects of drugs.

Hypokalemia, like bradycardia, contributes to the development of severe arrhythmias, especially cardiac rhythm disturbances, which can lead to death. The first measurement of the potassium content in the blood plasma should be carried out within the first week after the start of treatment. When hypokalemia is detected, the appointment of appropriate therapy is indicated.

Calcium in the blood plasma

Thiazide and thiazide-like diuretics reduce the excretion of calcium in the urine, which leads to a slight temporary increase in calcium in the blood plasma. Hypercalcemia with clinical manifestations may be the result of previously undiagnosed hyperparathyroidism.

It is necessary to cancel the intake of diuretics before examining the function of parathyroid glands.

Blood plasma glucose

The control of glucose concentration in patients with diabetes mellitus is shown, especially in the presence of hypokalemia.

Uric acid

Patients suffering from gout may increase the frequency of gout attacks or exacerbation of its course.

Diuretics and kidney function

Thiazide and thiazide-like diuretics are most effective in patients with normal or slightly decreased renal function (creatinine plasma in adults <25 mg / L or 220 μmol / L). The concentration of creatinine in the blood plasma in elderly patients is estimated depending on age, body weight and sex.

At the beginning of treatment, patients may experience decreased glomerular filtration rate due to hypovolemia, which may be associated with loss of water and sodium due to the action of diuretics. This may be associated with an increase in the concentration of uric acid and creatinine in the blood plasma. With preserved kidney function, such a transient functional renal failure, as a rule, passes without complications. However, in the presence of renal failure, the general condition of patients may worsen.

Athletes

Indapamide can give a positive result of doping control in athletes.

Associated with lisinopril

Symptomatic arterial hypotension

In most pronounced decrease in blood pressure associated with hypovolemia caused by the use of diuretics, decrease the amount of salt in the diet, dialysis, vomiting or diarrhea (see. "Interactions with other drugs," "Side effect"). In patients with CHF, regardless of whether it is associated with renal insufficiency, it is possible to develop arterial hypotension. It was found that in patients with severe heart failure such a condition occurs more often due to the appointment of high doses of diuretics, hyponatremia or impaired renal function. Such patients require thorough medical supervision (it is necessary to carefully select the dose of lisinopril and diuretics). The same guidelines apply to patients with ischemic heart disease and cerebrovascular insufficiency, in whom a sharp decrease in blood pressure can lead to myocardial infarction or stroke.

If the patient's blood pressure is significantly reduced, it is recommended to place it in the lying position, if necessary, inject 0.9% sodium chloride solution intravenously.

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

In patients with CHF, but with normal or reduced BP, the use of lisinopril may lead to a decrease in blood pressure; this usually does not serve as a basis for drug discontinuation. In the event that arterial hypotension turns into symptomatic, it is necessary to reduce the dose of the drug or stop treatment with the drug. In patients at risk of developing symptomatic arterial hypotension (with low-salt or salt-free diet), regardless of the presence of hyponatremia, as well as in patients receiving diuretics in high doses, it is necessary to compensate for hypovolemia or a lack of sodium before treatment.

It is necessary to monitor blood pressure when taking the first dose of lisinopril.

Acute myocardial infarction

Recommended standard treatment (thrombolytics, acetylsalicylic acid, beta-blockers). Lisinopril can be used concurrently with intravenous nitroglycerin or transdermal nitroglycerin.

In patients with acute myocardial infarction and risk of further deterioration of hemodynamics, worsening of symptoms after the appointment of vasodilators, therapy with lisinopril should not begin. These are patients with systolic blood pressure ≤ 100 mm Hg. Art.and patients with cardiogenic shock. In patients with systolic blood pressure <120 mm Hg. Art. During the first three days after myocardial infarction, a dose reduction was shown. In patients with systolic blood pressure ≤ 100 mm Hg. Art. the maintenance dose should be reduced to 5 mg (or temporarily to 2.5 mg). In patients with persistent arterial hypotension (systolic BP <90 mm Hg for 1 hour or more), the withdrawal of lisinopril is indicated.

Impaired renal function

In patients with CHF, a significant reduction in blood pressure on the background of the appointment of ACE inhibitors can lead to an increase in renal dysfunction. Cases of acute renal failure have been reported.

In patients with bilateral stenosis of the renal arteries or stenosis of the renal artery of a single kidney, an increase in the concentration of urea and serum creatinine was noted in patients with ACE inhibitors; usually such violations were transient and discontinued after the abolition of therapy. They were more common in patients with renal insufficiency.

In patients with acute myocardial infarction and severe renal dysfunction (serum creatinine concentration> 177 μmol / l and / or proteinuria> 500 mg / day) lisinopril should not be appointed. With the development of renal dysfunction during treatment (serum creatinine> 265 μmol / L or doubling as compared to the baseline), the withdrawal of lisinopril is indicated.

Hypersensitivity, angioedema

In rare cases, against the background of the use of ACE inhibitors, including lisinopril, there was a development of angioedema, edema, lips, tongue, epiglottis and / or larynx. In such cases, immediate withdrawal of lisinopril is required; the control of a condition of patients before the full permission of a symptomatology is shown. Usually angioedema and edema of the face and lips is temporary and does not require treatment; nevertheless, prescription of antihistamines is possible. The angioedema of the larynx can lead to death. Swelling of the tongue, epiglottis or larynx can lead to secondary airway obstruction. In this case, you must immediately enter 0.3-0.5 ml of a 1: 1000 solution of epinephrine subcutaneously, as well as provide airway patency.

In rare cases, on the background of therapy with ACE inhibitors, angioedema of the intestine developed.In this case, patients had abdominal pain as an isolated symptom or in combination with nausea or vomiting, in some cases without a previous angioedema and at a normal level of C1-esterase. The diagnosis was established using computed tomography of the abdominal organs, ultrasound or during surgery. Symptoms disappeared after discontinuation of ACE inhibitors. Therefore, patients with abdominal pain receiving ACE inhibitors should take into account the possibility of developing angioedema of the intestine during differential diagnosis.

In patients with angioedema, a history that is not associated with the administration of ACE inhibitors, the risk of developing it with ACE inhibitors is higher (see "Contraindications").

Anaphylactic reactions, Obligatory with desensitization to hymenoptera insects

In very rare cases, in patients taking ACE inhibitors during the desensitization to Hymenoptera, the development of life-threatening anaphylactic reactions is possible, therefore, it is necessary to temporarily abolish ACE inhibitors before desensitization.

Patients on hemodialysis

Anaphylactic reactions also occurred in patients who underwent hemodialysis using dialysis membranes with high permeability (for example, AN69), who simultaneously received ACE inhibitors. Such patients show the use of other dialysis membranes or other antihypertensive drugs.

Cough

Therapy with ACE inhibitors can cause a cough, which should be considered when conducting differential diagnosis. A prolonged dry cough usually stops after the withdrawal of ACE inhibitors.

Surgical interventions / general anesthesia

The use of antihypertensive drugs with volumetric surgery or during general anesthesia can lead to inhibition of the formation of angiotensin II due to compensatory renin secretion.

A significant reduction in blood pressure associated with this effect can be prevented by an increase in the volume of circulating blood.

Patients taking ACE inhibitors should inform the surgeon / anesthesiologist prior to surgery (including dental procedures).

Blood serum potassium

There have been reports of hyperkalemia.

The risk factors for hyperkalemia include renal failure, diabetes, potassium-sparing diuretics (spironolactone, triamterene and amiloride), the use of potassium preparations and salt substitutes based on potassium, especially in patients with impaired renal function.

If it is necessary to combine the use of lisinopril and these drugs, regular monitoring of the serum potassium concentration is indicated.

Double blockade of RAAS

It has been proven that simultaneous administration of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure). Thus, the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren for double blockade of RAAS is not recommended.

If there are absolute indications for a double blockade of RAAS, then it should be performed under the close supervision of a specialist with frequent monitoring of kidney function, electrolyte content and blood pressure.

Simultaneous use of ACE inhibitors with drugs containing aliskiren, contraindicated in patients with diabetes mellitus and / or with moderate or severe renal insufficiency (GFR less than 60 mL / min / 1.73 m² body surface area) and is not recommended in other patients;

Simultaneous use of ACE inhibitors with angiotensin II receptor antagonists contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

Neutropenia / agranulocytosis / thrombocytopenia / anemia

Against the background of the administration of ACE inhibitors, neutropenia / agranulocytosis, thrombocytopenia and anemia can occur. In patients with normal renal function and in the absence of other aggravating factors, neutropenia develops rarely. With special caution, you should prescribe the drug Ecapress to patients with systemic connective tissue diseases, when taking immunosuppressants, allopurinol or procainamide, or a combination of these risk factors, especially for patients with impaired renal function. Some patients had severe infections, in some cases resistant to intensive antibiotic therapy. With the appointment of the drug Ecapress, it is recommended that such patients periodically check the number of leukocytes in the blood plasma.Patients should inform the doctor of any signs of infectious diseases (eg, sore throat, fever).

Mitral stenosis / aortic stenosis / hypertrophic cardiomyopathy

ACE inhibitors should be administered with caution to patients with mitral stenosis, as well as to patients with obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic cardiomyopathy).

Liver failure

Very rarely, when taking ACE inhibitors, cholestatic jaundice occurs. With the progression of this syndrome, fulminant liver necrosis develops, sometimes with a fatal outcome. The mechanism of development of this syndrome is unclear. If jaundice or a significant increase in the activity of "liver" enzymes against the background of taking ACE inhibitors, you should abolish the drug Ecupress and carefully observe the patient.

Ethnic differences

In patients of the Negroid race, angioneurotic edema develops more often than in representatives of other races against the background of the administration of ACE inhibitors. ACE inhibitors may have a less pronounced antihypertensive effect in patients of the Negroid race compared with representatives of other races.Perhaps this difference is due to the fact that patients with arterial hypertension of the Negroid race are more likely to have low renin activity.

Lactose

The drug contains lactose monohydrate, so it should not be taken to patients with rare hereditary intolerance to galactose, lactase deficiency, or glucose-galactose malabsorption syndrome.

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

There are no data on the effect of the drug Ecapress on the ability to drive vehicles and control mechanisms. Given the possibility of lowering blood pressure, the risk of dizziness, drowsiness and similar side effects, patients should be careful in carrying out potentially hazardous activities that require special attention and quick response (driving, working with moving mechanisms, dispatcher and operator work, etc.) .

Form release / dosage:

Capsules with modified release, 5 mg + 1.5 mg + 10 mg, 10 mg + 1.5 mg + 20 mg, 5 mg + 1.5 mg + 20 mg.

Packaging:

For 14 capsules in a blister of PVC / PE / PVDC and aluminum foil. For 1, 2, 4 or 8 blisters together with the instructions for use are placed in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-004622

Date of registration:26.12.2017

Expiration Date:26.12.2022

The owner of the registration certificate:GEDEON RICHTER, OJSC GEDEON RICHTER, OJSC Hungary

Manufacturer: & nbsp

GEDEON RICHTER, Ltd. Hungary

Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary

Information update date: & nbsp19.02.2018

Illustrated instructions

Instructions

Ecapress (Ekvapress)