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

Excipients: cellulose microcrystalline (type 112) 114.71 mg, microcrystalline cellulose (type 14) 57,355 mg, polacrilin potassium 10 mg, silicon dioxide colloid 5 mg, magnesium stearate 2 mg.

Dosage of 5 mg + 8 mg

Active substances: Amlodipine besylate 6.935 mg (equivalent to 5 mg of amlodipine), perindopril erbumine 8 mg.

Excipients: cellulose microcrystalline (type 112) 110.71 mg, microcrystalline cellulose (type 14) 57,355 mg, polacrilin potassium 10 mg, silicon dioxide colloid 5 mg, magnesium stearate 2 mg.

Dosage of 10 mg + 4 mg

Active substances: amlodipine besylate 13.87 mg (equivalent to 10 mg of amlodipine), perindopril erbumine 4 mg.

Excipients: cellulose microcrystalline (type 112) 233.42 mg, microcrystalline cellulose (type 14) 114.71 mg, polacrilin potassium 20 mg, silicon dioxide colloid 10 mg, magnesium stearate 4 mg.

Dosage of 10 mg + 8 mg

Active substances: Amlodipine besylate 13.87 mg (equivalent to 10 mg of amlodipine), perindopril erbumine 8 mg.

Excipients: cellulose microcrystalline (type 112) 229.42 mg, microcrystalline cellulose (type 14) 114.71 mg, polacrilin potassium 20 mg, silicon dioxide colloid 10 mg, magnesium stearate 4 mg.

Description:

Dosage 5 mg + 4 mg

White or almost white, round, flat tablets with chamfer and engraving "CH3" on one side.

Dosage of 5 mg + 8 mg

White or almost white, round, flat tablets with chamfering and engraving "CH4" on one side.

Dosage of 10 mg + 4 mg

White or almost white, round, flat tablets with chamfer and engraving "CH5" on one side.

Dosage of 10 mg + 8 mg

White or almost white, round, flat tablets with chamfer and engraving "CH6" on one side.

Pharmacotherapeutic group:Antihypertensive agent combined (ACE inhibitor + BCCC)

ATX: & nbsp

C.09.A.A.04 Perindopril

C.08.C.A.01 Amlodipine

Pharmacodynamics:

Amlopress® is a fixed combination of active substances: amlodipine and perindopril.

Perindopril

Perindopril is an inhibitor of the enzyme converting angiotensin I to angiotensin II (an angiotensin-converting enzyme inhibitor).

Angiotensin-converting enzyme, or kinase II, is an exopeptidase that carries out both the conversion of angiotensin I into a vasoconstrictor (vasoconstrictor) angiotensin II, and the destruction of bradykinin having a vasodilating action to an inactive heptapeptide. As a result, perindopril reduces the secretion of aldosterone.

Since ACE inactivates bradykinin, ACE inhibition is accompanied by an increase in the activity of both the circulating and tissue kallikrein-kinin system, and the system of prostaglandins is also activated. It is possible that this effect is part of the mechanism of antihypertensive action of ACE inhibitors, as well as the mechanism of development of some side effects of drugs of this class (for example, cough).

Perindopril acts through its active metabolite perindoprilata. Other metabolites did not show in vitro ability to inhibit the action of ACE.

Clinical efficacy and safety

Arterial hypertension

Perindopril is effective in the treatment of arterial hypertension of any severity. Against the background of the use of perindopril, both systolic and diastolic blood pressure (BP) decrease in the "lying" and "standing" positions. Perindopril reduces overall peripheral vascular resistance (OPSS), which leads to a decrease in blood pressure, while peripheral blood flow accelerates without changing the heart rate (heart rate).

Usually, perindopril leads to an increase in renal blood flow, the glomerular filtration rate (GFR) does not change.

Antihypertensive effect of perindopril reaches a maximum after 4-6 hours after a single oral intake and persists for 24 hours. After 24 hours after ingestion, a residual (about 80%) residual inhibition of ACE is observed.

Decrease in blood pressure is achieved quickly enough. In patients with a positive response to treatment, BP normalization occurs within a month and persists without the development of tachycardia.

The termination of treatment is not accompanied by the development of the "withdrawal" syndrome. Perindopril has a vasodilating effect, helps restore the elasticity of large arteries and the structure of the vascular wall of small arteries, and also reduces left ventricular hypertrophy.

Heart failure

Perindopril normalizes the heart, reducing preload and postnagruzku.

In patients with chronic heart failure (CHF) who received perindopril, observed:

- Decrease in the filling pressure of the left and right ventricles of the heart;

- reduction of the OPSS;

- increased cardiac output and an increase in cardiac index.

The study showed that the change in blood pressure in patients with mild-to-moderate heart failure after first ingestion of 2.5 mg perindopril did not differ statistically significantly from changes in blood pressure in patients after placebo.

Cerebrovascular diseases

The effect of active perindopril therapy (either as monotherapy or in combination with indapamide) on the risk of recurrent stroke was studied in patients with a history of cerebrovascular disease.

The results of the study showed that treatment with perindopril significantly reduces the risk of recurrent stroke (both ischemic and hemorrhagic) by 28% (95% CI (17; 38), p <0.0001) compared with placebo (10.1% compared with 13.8%).

In addition, there was a significant risk reduction:

- fatal or disabling stroke;

- Major cardiovascular complications, including myocardial infarction, including fatal outcome;

- dementia associated with stroke; serious deterioration of cognitive functions.

These therapeutic advantages were observed both in patients with arterial hypertension and under normal BP irrespective of age, sex, the presence or absence of diabetes mellitus and the type of stroke.

Stable ischemic heart disease (CHD)

It has been shown that in patients with stable coronary artery disease there is a significant reduction in the absolute risk of complications provided by the main efficacy criterion (mortality from cardiovascular diseases, the incidence of nonfatal infarction, compared with 10 mg perindopril arginine) perindopril 8 mg once daily (equivalent to 10 mg perindopril arginine) myocardial and / or cardiac arrest followed by successful resuscitation), by 1.9%. In patients who had previous myocardial infarction or coronary revascularization, the absolute risk reduction was 2.2% compared with the placebo group.

Amlodipine

Amlodipine is a derivative of dihydropyridine, blocks "slow" calcium channels and transmembrane transfer of calcium ions to cardiomyocytes and smooth muscle cells of the vessels (affects more smooth muscle vessels,than on cardiomyocytes). Antianginal action is due to the expansion of coronary and peripheral arteries and arterioles:

1. It expands the peripheral arterioles and, thus, reduces the overall peripheral resistance (afterload), with the heart rate practically unchanged, which leads to a reduction in energy consumption and myocardial oxygen demand.

2. Expands coronary and peripheral arteries and arterioles in both normal and ischemic zones of the myocardium, which increases the flow of oxygen into the myocardium in patients with vasospastic angina (Prinzmetal angina) and prevents the development of coronarospasm caused by smoking.

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

Amlodipine 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 reduction in blood pressure for 24 hours (in the patient's "lying" and "standing" position).

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 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 6-10 hours after taking amlodipine, the duration of the effect is 24 hours.

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

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

Pharmacokinetics:

Perindopril

Suction

After oral administration perindopril quickly absorbed from the gastrointestinal tract (the maximum concentration in the blood plasma is reached within 1 hour).

Metabolism

Perindopril does not have pharmacological activity. Approximately 27% of the total amount of absorbed perindopril is converted to the active metabolite perindoprilat. In addition to perindoprilata, 5 metabolites are formed in the metabolism process - all of them are inactive substances.

The half-life (T_1/2) of perindopril from plasma is 1 hour. The maximum concentration of perindoprilat in blood plasma is reached within 3-4 hours. The intake of perindopril during meals is accompanied by a decrease in the conversion of perindopril to perindoprilat, thus reducing the bioavailability of the drug. therefore perindopril should be taken 1 time per day, in the morning, before eating.

Distribution and binding to blood plasma proteins

The volume of distribution of unbound perindoprilata is about 0.2 l / kg. The degree of binding perindoprilata with blood plasma proteins, mainly with ACE, is dose-dependent and is 20%.

Excretion

Perindoprilat is excreted by the kidneys, T_1/2free fraction is 3-5 hours. The final T_1/2is approximately 17 hours, the equilibrium state is reached within four days.

Fermacokinetics in specific patient groups

The excretion of perindoprilat slows down in old age, and in patients with cardiac and renal insufficiency. At an individual choice of a dose it is necessary to consider a degree of disturbance of function of kidneys (a creatinine clearance).

The dialytic clearance of perindoprilat is 70 ml / min.

In patients with cirrhosis of the liver the hepatic clearance of perindopril is reduced by half. However, the amount of perindoprilat formed does not decrease, so no dose adjustment is required.

Amlodipine

Suction

After oral administration amlodipine well absorbed from the gastrointestinal tract. The average absolute bioavailability is 64-80%. The maximum concentration in serum is observed after 6-12 hours. Equilibrium concentrations 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 volume of distribution is approximately 21 l / kg, indicating that most of the amlodipine is in the tissues, and the smaller is in the blood. The connection with plasma proteins is approximately 97.5%.Food intake does not affect the absorption of amlodipine. Penetrates through the blood-brain barrier.

Metabolism / Inference

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

After a single admission of amlodipine T_1/2 varies from 35 hours to 50 hours, with repeated use of T_1/2 is approximately 45 hours. About 60% of the ingested dose is excreted by the kidneys mainly in the form of metabolites, 10% - unchanged, and 20-25% - through the intestines with bile. The total clearance of amlodipine is 0.116 ml / s / kg (7 ml / min / kg, 0.42 l / h / kg).

Pharmacokinetics in specific patient groups

Patients with renal insufficiency

Renal failure does not significantly affect the kinetics of amlodipine. Amlodipine penetrates the blood-brain barrier. When hemodialysis is not removed.

Patients with hepatic insufficiency

Elongation T_1/2the patients with hepatic insufficiency suggest that with prolonged use, the cumulation of amlodipine in the body will be higher (T_1/2lengthened to 60 h).

Patients of advanced age (over 65 years)

In elderly patients, excretion of amlodipine is delayed (T_1/2- 65 h) compared with young patients, but this difference has no clinical significance.

Indications:

Amlopress® is indicated as a substitute therapy for patients with adequate control of blood pressure against the background of simultaneous administration of amlodipine and perindopril at the same doses as in a fixed combination.

Contraindications:

- Hypersensitivity to perindopril or any other ACE inhibitor;

- hypersensitivity to amlodipine or any other dihydropyridine derivative;

- hypersensitivity to the excipients included in the preparation;

- angioedema (angioedema) in history, associated with the taking of an ACE inhibitor;

- hereditary / idiopathic angioedema;

- severe arterial hypotension (systolic blood pressure less than 90 mm Hg);

- Obstruction of the outflow tract of the left ventricle (including severe aortic stenosis);

- hemodynamically unstable heart failure after myocardial infarction;

- shock (including cardiogenic);

- renal dysfunction (CC less than 60 ml / min);

- simultaneous use of perindopril with aliskiren and preparations containing aliskiren, in patients with diabetes mellitus or renal dysfunction (GFR <60 mL / min / 1.73 m² body surface area) (see sections "Special instructions" and "Interaction with other medicinal products");

- pregnancy and the period of breastfeeding (see the section on "Application during pregnancy and during breast-feeding");

- age under 18 years (efficiency and safety not established).

Carefully:

Reduction of the volume of circulating blood (caused by the use of diuretics, diet low in table salt, vomiting, diarrhea), cerebrovascular diseases, angina (risk of excessive blood pressure lowering); chronic heart failure III-IV functional class by classification NYHA, intake of potassium-sparing diuretics, potassium preparations, potassium-containing substitutes for edible salt and lithium preparations, renova-vascular hypertension, bilateral stenosis of the renal arteries or in the presence of only one functioning kidney, chronic renal failure; systemic connective tissue diseases (systemic lupus erythematosus, scleroderma), patients,receiving immunosuppressive therapy, allopurinol or procainamide; Hyperkalemia (see section "Interaction with other drugs"); stenosis of the aortic valve, hypertrophic obstructive cardiomyopathy; patients on hemodialysis using high-flow polyacrylonitrile membranes; apheresis of low-density lipoproteins (LDL) (hardware removal of cholesterol from the blood); patients after kidney transplantation; simultaneous conduct of desensitizing therapy with allergens; surgical intervention / general anesthesia; use in patients with diabetes mellitus receiving hypoglycemic agents or insulin; the use of Negroid race in patients, hepatic insufficiency, chronic heart failure of non-ischemic etiology III-IV functional class by classification NYHA, acute myocardial infarction (and within 1 month after myocardial infarction), use in patients with weakness syndrome of the sinus node (severe tachycardia or bradycardia), stenosis of the mitral valve, arterial hypotension, while simultaneous application with inhibitors or inducers of isoenzyme CYP3A4, the elderly age.

Pregnancy and lactation:

Pregnancy

Amlopress® is contraindicated during pregnancy.

Adequate strictly controlled clinical studies to study the effect of Amlopress ® during pregnancy have not been conducted. The use of active ingredients in the preparation of pregnant women is contraindicated or not recommended.

Women of reproductive age should apply adequate methods of contraception. If pregnancy is established, taking Amlopress® should be stopped immediately and, if necessary, an alternative treatment should be prescribed.

He It is necessary to start therapy with Amlopress ® during pregnancy. If it is necessary to continue therapy, patients planning a pregnancy should switch to alternative antihypertensive therapy with an established safety profile during pregnancy.

Perindopril not recommended for use in the first trimester of pregnancy. When planning or confirming pregnancy, you should immediately stop taking perindopril and switch to alternative therapy. Since no relevant controlled studies have been performed in humans, clinical data on the effect of ACE inhibitors in the first trimester of pregnancy are inadequate.In some cases, the use of ACE inhibitors in the first trimester of pregnancy was not accompanied by the development of any malformations associated with fetotoxicity (see the information below).

Perindopril is contraindicated in the II and III trimesters of pregnancy, as there are data on the manifestation of fetotoxicity (decreased renal function, oligohydramnion (pronounced decrease in amniotic fluid volume), slowing ossification of the skull bones) and complications in the newborn (renal dysfunction, arterial hypotension, hyperkalemia) . If perindopril was used in II and / or III trimesters of pregnancy, it is necessary to perform ultrasound examination of the kidneys and skull of the fetus. Safety of use amlodipine during pregnancy and lactation is not established. In experimental animal studies fetotoxic and embryotoxic effects of amlodipine have been established when applied in high doses. The use of amlodipine during pregnancy is possible only if the benefit to the mother exceeds the risk for the fetus and the newborn.

Breastfeeding period

The use of Amlopress® is contraindicated during breastfeeding. It is not known whether the active substances are excreted into the human breast milk. However, it is known that other BCCC - dihydropyridine derivatives are excreted into breast milk. The active substances of the preparation Amlopress® penetrate into the milk of lactating rats.

Fertility

No effect of perindopril on reproductive function or fertility was detected.

In some patients receiving blockers of "slow" calcium channels, biochemical changes in the head of spermatozoa were detected. However, at present there is insufficient clinical data on the potential impact of amlodipine on fertility. In studies on rats, undesirable effects on fertility in males were identified.

Dosing and Administration:

Mode of application

Amlopress® is recommended to be taken once a day, in the morning before meals, with a sufficient amount of water (100 ml).

Dosing regimen

As a rule, drugs containing fixed combinations of drugs funds are not suitable for the initial course of therapy.

The dose of Amlopress® is selected after previous titration of doses of individual components of the drug: amlodipine and perindopril in patients with arterial hypertension and / or coronary heart disease.

Amlopress® is indicated only for those patients whose titrated optimal maintenance doses of amlodipine and perindopril are:

- for the preparation Amlopress®, tablets, 5 mg + 4 mg - amlodipine 5 mg and perindopril 4 mg;

- for the preparation Amlopress®, tablets, 5 mg + 8 mg - amlodipine 5 mg and perindopril 8 mg respectively;

- for the preparation Amlopress®, tablets, 10 mg + 4 mg - amlodipine 10 mg and perindopril 4 mg respectively;

- for the preparation Amlopress®, tablets, 10 mg + 8 mg - amlodipine 10 mg and perindopril 8 mg respectively.

In the event that a dose adjustment is necessary, titration of the doses should be carried out using amlodipine and perindopril in monotherapy.

The recommended dose is 1 tablet per day. The maximum daily dose is 1 tablet.

Special patient groups

Patients with renal insufficiency

In patients with renal insufficiency, excretion of perindoprilate is slowed. Therefore, a medical examination should include regular monitoring of creatinine concentration and potassium content inblood serum.

Amlopress® can be given to patients with a creatinine clearance of CC ≥ 60 mL / min.

It is not recommended to apply the drug to patients with CC <60 ml / min (see the section "Contraindications"). Such patients are recommended individual selection of doses of individual components.

The change in the concentration of amlodipine in the blood plasma does not correlate with the degree of renal failure.

Patients with hepatic insufficiency

For patients with mild or moderate hepatic insufficiency, dose selection should be performed with caution. It is recommended to start taking the drug from low doses (see sections "Dosing and Administration" and "Special instructions"). The search for an optimal initial and maintenance dose for patients with hepatic insufficiency should be carried out individually, using amlodipine and perindopril preparations in monotherapy. The pharmacokinetics of amlodipine in patients with severe hepatic insufficiency has not been studied. For such patients, amlodipine should be taken at the lowest dose and increased gradually.

Children and adolescents (under 18 years of age)

The efficacy and safety of Amlopress® in children and adolescents is notinstalled.

Patients of advanced age (over 65 years)

In elderly patients the excretion of perindoprilate is slowed down. Therefore, a medical examination should include regular monitoring of the concentration of creatinine and the content of potassium in the blood serum.

Side effects:

During the monotherapy with perindopril and amlodipine, the following adverse drug reactions (NLR) were observed:

NLR are represented by system-organ classes in accordance with the classification MedDRA and with the frequency of occurrence:

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

Often - 1/100 appointments (≥ 1% and <10%)

Uncommon - 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%).

Within each group, adverse reactions are presented in descending order of severity.

Perindopril

The safety profile of perindopril is consistent with the safety profile of ACE inhibitors.

The most common adverse events reported in clinical trials and have been observed in the application of perindopril are: dizziness, headache, paresthesia, vertigo, blurred vision, ringing in the ears, excessive reduction of blood pressure, cough, shortness of breath, abdominal pain, constipation, diarrhea, taste perversion, dyspepsia, nausea,vomiting, skin itching, skin rash, muscle spasms and asthenia.

Disorders from the metabolism and nutrition

infrequently: hypoglycemia (see the sections "Special instructions" and "Interaction with other medicines"), hyperkalaemia reversible after the abolition of perindopril (see section "Special instructions"), hyponatremia.

Disorders of the psyche

infrequently: mood lability;

rarely: confusion of consciousness.

Disturbances from the nervous system

often: headache, dizziness, visual impairment, muscle cramps, paresthesia, vertigo;

infrequently: sleep disorders, drowsiness, fainting.

Hearing disorders and labyrinthine disorders

often: noise in ears.

Violations from the heart and blood vessels

often: excessive BP reduction and related symptoms;

infrequently: vasculitis, tachycardia, palpitation;

rarely: arrhythmia, stenocardia, myocardial infarction and stroke, it is possible to develop secondary severe arterial hypotension in patients of this risk group.

Disturbances from the respiratory system, chest and mediastinal organs

often: cough, difficulty breathing; infrequently: bronchospasm;

rarely: eosinophilic pneumonia, rhinitis.

Disorders from the digestive system

often: nausea, vomiting, abdominal pain, taste perversion, diarrhea, constipation, indigestion;

infrequently: dryness of the oral mucosa;

rarely: angioedema of the intestine (see section "Special instructions");

rarely: pancreatitis.

Disturbances from the liver and bile ducts

rarely: cholestatic or cytolytic jaundice.

Disturbances from the skin and subcutaneous tissues

often: skin itching, rash;

infrequently: angioedema, swelling of the face, lips, extremities, mucous membranes, tongue, vocal cords and / or larynx, urticaria, photosensitivity, pemphigus, increased sweating;

rarely: erythema multiforme.

Disturbances from musculoskeletal and connective tissue

infrequently: arthralgia, myalgia.

Disorders from the kidneys and urinary tract

infrequently: kidney failure;

rarely: acute renal failure.

Violations of the genitals and mammary gland

infrequently: erectile disfunction.

General disorders and disorders at the site of administration

often: asthenia;

infrequently: pain in the chest, peripheral edema, weakness, fever, falls.

Impact on the results of laboratory and instrumental studies

infrequently: eosinophilia, an increase in the concentration of urea and creatinine in the blood plasma;

rarely: increased serum bilirubin concentration and increased activity of "hepatic" enzymes;

rarely: reduction of hemoglobin and hematocrit, thrombocytopenia, leukopenia / neutropenia, single cases of agranulocytosis or pancytopenia. Possible development of hemolytic anemia, due to deficiency of glucose-6-phosphate dehydrogenase.

Amlodipine

Violations of the blood and lymphatic system

rarely: thrombocytopenic purpura, leukopenia, thrombocytopenia.

Immune system disorders

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

rarely: angioedema, erythema multiforme.

Disorders from the metabolism and nutrition

rarely: hyperglycemia.

Disorders of the psyche

often: drowsiness;

infrequently: lability of mood, unusual dreams, anxiety, depression;

rarely: amnesia, apathy, agitation.

Disturbances from the nervous system

often: increased fatigue, dizziness, headache;

infrequently: increased excitability, asthenia, hypoesthesia, paresthesia, peripheral neuropathy, tremor, insomnia, taste perversion, chills;

rarely: ataxia, parosmia, migraine, increased sweating.

Individual cases of extrapyramidal syndrome have been reported.

Disturbances on the part of the organ of sight

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

Hearing disorders and labyrinthine disorders

infrequently: tinnitus.

Violations from the heart and blood vessels

often: sensation of palpitations, peripheral edema (ankles and feet), "tides" of blood to the skin of the face;

infrequently: excessive decrease in blood pressure;

rarely: fainting, shortness of breath, vasculitis, orthostatic hypotension, development or exacerbation of CHF, heart rhythm disturbances (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction, chest pain.

Disturbances from the respiratory system, chest and mediastinal organs

infrequently: shortness of breath, rhinitis, nosebleeds;

rarely: cough.

Disorders from the digestive system

often: abdominal pain, nausea;

infrequently: vomiting, changes in the bowel movement (including constipation, flatulence), dyspepsia, diarrhea, anorexia, dryness of the oral mucosa, thirst;

rarely: gingival hyperplasia, increased appetite;

rarely: gastritis, pancreatitis.

Disturbances from the liver and bile ducts

rarely: hyperbilirubinemia, jaundice (usually cholestatic), increased activity of "hepatic" enzymes, hepatitis.

Disturbances from the skin and subcutaneous tissues

rarely: dermatitis;

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

Disturbances from musculoskeletal and connective tissue

infrequently: arthralgia, muscle cramps, myalgia, back pain, arthrosis; rarely: myasthenia gravis.

Disorders from the kidneys and urinary tract

infrequently: frequent urination, painful urination, nocturia;

rarely: dysuria, polyuria.

Violations of the genitals and mammary gland

infrequently: erectile dysfunction, gynecomastia.

General disorders and disorders at the site of administration

infrequently: increase / decrease in body weight, general malaise, pain of unspecified localization.

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

Overdose:

There is no information about an overdose of Amlopress ® in humans.

Perindopril

Symptoms: excessive decrease in blood pressure, collapse, disturbed water-electrolyte metabolism (such as an increase in potassium and a decrease in serum sodium), kidney failure, hyperventilation, tachycardia, palpitations, dizziness, bradycardia, anxiety and cough.

Treatment: with a significant decrease in blood pressure, the patient should be transferred to the "lying" position on the back with raised legs.

Emergency measures are reduced to excretion of perindopril from the body: washing the stomach and / or taking activated carbon and correcting the water-electrolyte balance. Urgent replenishment of the volume of circulating blood is necessary. If necessary, you can enter intravenously a solution of catecholamines.When developing a bradycardia that is stable to treatment, it may be necessary to implant an artificial pacemaker. The indicators of the basic physiological functions, the content of electrolytes and the concentration of serum creatinine should be under constant control. Perindopril can be removed from the systemic blood flow by means of hemodialysis. Dialysis should avoid the use of high-flow polyacrylonitrile membranes.

Amlodipine

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

Treatment: (especially in the first 2 hours after an overdose), gastric lavage (in some cases), elevating the limbs, actively maintaining the function of the cardiovascular system, monitoring the cardiovascular and respiratory systems, monitoring the volume of circulating blood and diuresis .

In the absence of contraindications, it may be useful to use vasoconstrictorspreparations for the restoration of vascular tone and blood pressure. Intravenous calcium gluconate is used. Because the amlodipine is largely associated with serum proteins, hemodialysis is ineffective.

Interaction:

Perindopril

Medicines that cause hyperkalemia

Some drugs or preparations of other pharmacological classes may increase the risk of hyperkalemia: aliskiren and aliskirensoderzhaschie preparations, potassium preparations kalisodergaszczye salt substitutes and nutritional supplements, potassium-sparing diuretics, ACE inhibitors, angiotensin receptor antagonists II (ARA II), non-steroidal anti-inflammatory drugs (NSAIDS), heparin, immunosuppressants, such as ciclosporin or tacrolimus, trimethoprim. The combination of these drugs increases the risk of hyperkalemia.

Simultaneous use is contraindicated (see section "Contraindications").

Aliskiren. In patients with diabetes mellitus or renal dysfunction (GFR <60 mL / min / 1.73 m² body surface area) increases the risk of hyperkalemia, deterioration of renal function and increased incidence of cardiovascular morbidity and mortality.

Simultaneous use is not recommended (see section "Special instructions").

Aliskiren. In patients without diabetes mellitus or renal dysfunction, there may be an increased risk of hyperkalemia, impaired renal function, and an increased incidence of cardiovascular morbidity and mortality.

Double blockade of the renin-angiotensin-aldosterone system (RAAS)

In the literature it was reported that in patients with established atherosclerotic disease, heart failure or diabetes with target organ damage, 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 content in blood and blood pressure.

It is not recommended simultaneous use of ACE inhibitors with APA II in patients with diabetic nephropathy.

Estramustine. Simultaneous application can lead to an increased risk of side effects, such as angioedema.

Potassium-sparing diuretics (such as triamterene, amiloride, spironolactone and its derivative eplerenone), potassium salts

Hyperkalemia (with a possible fatal outcome), especially in cases of impaired renal function (additional effects associated with hyperkalemia).

The combination of perindopril with the above medicines is not recommended (see section "Special instructions"). If, however, simultaneous application is shown, they should be used, observing safety precautions and regularly monitoring the potassium content in serum.

Features of the use of spironolactone in heart failure are described further in the text.

Lithium preparations. With simultaneous use of lithium drugs and ACE inhibitors, a reversible increase in serum lithium levels and associated toxic effects can be noted. Simultaneous use of perindopril and lithium preparations is not recommended. If this therapy is necessary, regular monitoring of lithium content in blood plasma should be carried out (see section "Special instructions").

Simultaneous application, which requires special care

Hypoglycemic agents (insulin, hypoglycemic agents for oral administration)

The use of ACE inhibitors can enhance the hypoglycemic effect of insulin and hypoglycemic agents for oral administration until the development of hypoglycemia. As a rule, this is observed in the first weeks of simultaneous therapy and in patients with impaired renal function.

Baclofen enhances the antihypertensive effect of ACE inhibitors. You should carefully monitor blood pressure and, if necessary, dosage of antihypertensive drugs.

Potassium-sparing diuretics. In patients receiving diuretics, especially those taking out fluid and / or salts, at the beginning of perindopril therapy, there may be an excessive decrease in blood pressure, the risk of which can be reduced by eliminating the diuretic, replenishing fluid loss or salts before starting perindopril therapy, and prescribing perindopril in low dose with a further gradual increase.

With arterial hypertension in patients receiving diuretics, especially those that remove fluid and / or salts, diuretics should be either discontinued before the use of an ACE inhibitor (with a potassium-sparing diuretic can be reassigned later)or an ACE inhibitor should be prescribed in a low dose with a further gradual increase.

When using diuretics in the case of chronic heart failure the ACE inhibitor should be administered at a low dose, possibly after a reduction in the dose of the simultaneously used potassium-sparing diuretic.

In all cases, renal function (creatinine concentration) should be monitored in the first weeks of the use of ACE inhibitors.

Potassium-sparing diuretics (eplerenone, spironolactone). The use of eplerenone or spironolactone in doses from 12.5 mg to 50 mg per day and low doses of ACE inhibitors:

- in the therapy of heart failure II-IV functional class by classification NYHA with a left ventricular ejection fraction <40% and previous ACE inhibitors and loop diuretics, there is a risk of hyperkalemia (possibly fatal), especially in the case of non-compliance with recommendations for this combination of drugs.

Before using this combination of drugs, you need to make sure that there is no hyperkalemia and renal dysfunction.

It is recommended to regularly monitor the concentration of creatinine and potassium in the blood serum: weekly in the first month of treatment and every month thereafter.

Non-steroidal anti-inflammatory drugs (including selective inhibitors of cyclooxygenase-2 (COX-2)), including acetylsalicylic acid ≥ 3 g / day

NSAIDs, including COX-2 inhibitors, can reduce the antihypertensive effect of ACE inhibitors. It has been found that NSAIDs, including COX-2 inhibitors, and ACE inhibitors have an additive effect on the increase in serum potassium, which can lead to impaired renal function. As a rule, these effects are reversible. In rare cases, acute renal failure may develop in elderly patients with an existing renal dysfunction or with dehydration of the body. Patients should receive an adequate amount of fluid, and it is recommended that the kidney function be carefully monitored, both at the beginning and during the treatment.

A simultaneous application that requires some caution

Hypotensive and vasodilating agents. The antihypertensive effect of the drugs can be intensified against the background of combined use with ACE inhibitors. The use of nitroglycerin and / or other vasodilators can lead to an additional antihypertensive effect.

Glyptins (linaglyptin, saxagliptin, sitagliptin, vitagliptin). Co-administration with ACE inhibitors may increase the risk of developing angioedema due to suppression of dipeptidyl peptidase IV (DPP-IV) activity with glyptin.

Tricyclic antidepressants / antipsychotics (antipsychotics) / drugs for general anesthesia. Co-administration with ACE inhibitors can lead to an increased antihypertensive effect.

Sympathomimetics can attenuate the antihypertensive effect of ACE inhibitors. When using this combination, the efficacy of ACE inhibitors should be evaluated regularly.

Preparations of gold. With the use of ACE inhibitors, including perindopril, patients receiving an intravenous preparation of gold (sodium aurotomy malate), was described symptom complex, which includes flushing of the facial skin, nausea, vomiting, arterial hypotension.

Amlodipine

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

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

Cimetidine: while the simultaneous use of amlodipine with cimetidine, the pharmacokinetics of amlodipine does not change.

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

Unlike other BCCI, with the combined use of amlodipine (III generation BCCC) with HDL, especially with indomethacin, no clinically significant interaction was found.

Strengthening of antianginal and antihypertensive action of BCCC is possible with simultaneous application with thiazide and looped diuretics, verapamil, ACE inhibitors, beta-adrenoblockers and nitrates. An increase in the antihypertensive effect of BCC is observed when combined with alpha-1-adrenoblockers, neuroleptics.

Vasodilators: it is possible to increase the antihypertensive effect of amlodipine. Caution should be exercised when using nitroglycerin, other nitrates or other vasodilators at the same time, as there may be an additional reduction in blood pressure.

Despite the fact that during the study of amlodipine a negative inotropic effect was not detected, some BCCCs can enhance the severity of negative inotropic action antiarrhythmic drugs, causing lengthening of the interval QT (eg, amiodarone and quinidine).

With the joint application of BCCI from lithium preparations (data for amlodipine are absent), an increase in the manifestation of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, ringing in the ears) is possible.

Antacids containing aluminum / magnesium: their single administration does not significantly affect the pharmacokinetics of amlodipine.

Sildenafil: a single dose of 100 mg of sildenafil in patients with essential hypertension does not affect the pharmacokinetics of amlodipine.

Atorvastatin: repeated administration of amlodipine at a dose of 10 mg and atorvastatin at a dose of 80 mg is not accompanied by significant changes in the pharmacokinetics of atorvastatin.

Simvastatin: simultaneous repeated use of amlodipine in a dose of 10 mg and simvastatin at a dose of 80 mg leads to an increase in the exposure of simvastatin by 77% compared with the same index for monotherapy with simvastatin. In such cases, the dosage of simvastatin should be limited to 20 mg per day in patients taking amlodipine.

Digoxin: with the simultaneous use of amlodipine with digoxin in healthy volunteers, serum concentration and renal clearance of digoxin do not change.

Ethanol (alcoholic beverages): with a single and repeated application in a dose of 10 mg amlodipine has no significant effect on the pharmacokinetics of ethanol.

Warfarin: Amlodipine does not affect the change in prothrombin time caused by warfarin.

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

Antiviral drugs (ritonavir). Increases plasma concentrations of BCCM, including amlodipine.

Neuroleptics and isoflurane: increased antihypertensive effect of dihydropyridine derivatives.

Calcium preparations can reduce the effect of BCCI.

Inhibitors of isoenzyme СUR3А4: with the simultaneous use of diltiazem 180 mg and amlodipine at a dose of 5 mg in elderly patients (from 69 to 87 years) with arterial hypertension, an increase in the system exposure of amlodipine by 57%. The simultaneous use of amlodipine and erythromycin in healthy volunteers (18 to 43 years) does not lead to significant changes in the systemic exposure of amlodipine (an increase in the area under the concentration-time curve by 22%).Despite the fact that the clinical significance of these effects is not fully understood, they can be more pronounced in elderly patients.

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

Inductors of isoenzyme CYP3A4, Data on the influence of inducers of isoenzyme CYP3A4 on the pharmacokinetics of amlodipine is not present. It is necessary to carefully monitor blood pressure while using amlodipine and isoenzyme inducers CYP3A4.

Dantrolene (intravenous):

In laboratory animals, cases of ventricular fibrillation with a lethal outcome and collapse on the background of verapamil and intravenous dantrolene were observed, accompanied by hyperkalemia. Due to the risk of hyperkalemia, simultaneous administration of "slow" calcium channel blockers, including amlodipine, in patients prone to malignant hyperthermia, as well as in the treatment of malignant hyperthermia, should be avoided.

Corticosteroids (mineral and glucocorticosteroids), tetracosactide: decrease in antihypertensive action (fluid retention and sodium ions due to the action of corticosteroids).

Special instructions:

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

If you forget to take the tablet of Amlopress®, wait and take the next pill at the usual time. Do not take a double dose to make up the missed dose.

When using a fixed combination of Amlopress®, recommendations for the use of individual components of the drug should be taken into account, described in detail below.

Perindopril

Stable IHD (reduced risk of cardiovascular complications in patients who had previous myocardial infarction and / or coronary revascularization)

If, during the first month of therapy with perindopril, there is an episode of unstable angina (significant or not), the relationship between benefit and risk should be assessed before continuing treatment.

Arterial hypotension

ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic arterial hypotension rarely develops in patients without concomitant diseases.The risk of excessive reduction in blood pressure is increased in patients with reduced circulating blood volume caused by diuretics, a diet low in table salt, hemodialysis, vomiting or diarrhea, as well as in patients with severe hypertension with high renin activity (see "Interaction with other medicines "and" Side effect "). Patients with an increased risk of developing symptomatic arterial hypotension should carefully monitor blood pressure, kidney function and serum potassium during perindopril therapy. This approach is also used in patients with angina or cerebrovascular disease, in which severe arterial hypotension can lead to myocardial infarction or cerebrovascular complications.

In the case of development of arterial hypotension the patient should be transferred to the "lying" position on the back with raised legs. If necessary, the volume of circulating blood should be replenished by intravenous administration of 0.9% sodium chloride solution.Transient arterial hypotension is not a reason for discontinuing treatment. After restoring the volume of circulating blood and blood pressure, treatment can be continued provided that the dose of perindopril is carefully selected.

In some patients with CHF and normal or low blood pressure perindopril may cause an additional decrease in blood pressure. This effect is predictable and usually does not require discontinuation of therapy. If symptoms of a marked decrease in blood pressure appear, reduce the dose of perindopril or stop taking it.

Mitral stenosis / aortic stenosis / hypertrophic obstructive cardiomyopathy

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

Renal insufficiency

In patients with renal insufficiency (CC <60 ml / min), the initial dose of perindopril should be selected according to the magnitude of the CC, depending on the response to treatment. Such patients need regular monitoring of QA and potassium content in the blood serum.

In patients with symptomatic heart failure, arterial hypotension, which develops during the initial period of therapy with ACE inhibitors, can lead to impaired renal function. Sometimes the developing acute renal failure is, as a rule, reversible.

In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney (especially in the presence of renal insufficiency), the concentration of urea and creatinine in the blood serum can increase with the therapy with ACE inhibitors.

The use of ACE inhibitors in patients with renal arterial hypertension is associated with an increased risk of severe arterial hypotension and renal failure. Treatment of such patients begins under careful medical supervision with the appointment of the drug in small doses and further adequate dose selection. During the first few weeks of therapy, it is necessary to cancel treatment with diuretics and monitor kidney function.

In some patients with hypertension without indicating the presence of a previous disease of the kidneys can increase the concentrationurea and creatinine in the blood serum, especially with the concomitant use of diuretics. These changes, as a rule, are not very pronounced and are reversible. The probability of these disorders is higher in patients with a history of renal insufficiency. In such cases it is recommended to reduce the dose of perindopril and / or to cancel the diuretic.

Hemodialysis

Several cases of persistent, life-threatening anaphylactic reactions have been reported in patients on hemodialysis using high-flow membranes (for example, AN69) on the background of therapy with ACE inhibitors. When using membranes of this type, the use of ACE inhibitors should be avoided.

Kidney Transplantation

Data on the use of perindopril in patients with kidney transplantation are absent.

Hypersensitivity / Angioedema

Angioedema of the face, upper and lower extremities, lips, mucous membranes, tongue, vocal cords and / or larynx can develop in patients receiving ACE inhibitors, including perindopril, in any period of therapy (see section "Side effect").When symptoms appear, taking the drug should be stopped immediately, and the patient should be observed until the signs of edema disappear completely. If the swelling affects only the face and lips, then its manifestations usually pass on their own, although antihistamines can be used to treat the symptoms.

Angioedema, accompanied by swelling of the larynx, can lead to death. Swelling of the tongue, vocal cords, or larynx can lead to airway obstruction. When these symptoms appear, urgent therapy is required, including subcutaneous injection of epinephrine (adrenaline) and / or ensuring airway patency. The patient should be under medical supervision until the symptoms disappear completely and persistently.

Patients with a history of Quinck's edema who are not associated with taking ACE inhibitors may be at increased risk of developing this drug when taking this drug (see "Contraindications").

In rare cases, against the background of therapy with ACE inhibitors, angioedema develops in the intestine. In this case, patients have abdominal pain,as an isolated symptom or in combination with nausea and vomiting, in some cases without a previous angioedema and at a normal level C1-esterase. The diagnosis was established using computed tomography of the abdominal region, ultrasound examination or surgical intervention. 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.

Anaphylactic reactions during the procedure of apheresis of low density lipoproteins (LDL)

In rare cases, life-threatening anaphylactic reactions may develop in patients receiving ACE inhibitors during the procedure for apheresis of LDL with dextran-sulfate absorption. To prevent anaphylactoid reaction, therapy with an ACE inhibitor should be temporarily discontinued before each apheresis procedure.

Anaphylactic reactions during desensitization

There are some reports of life-threatening anaphylactic reactions in patients,receiving ACE inhibitors, during the desensitizing therapy with bee venom (bees, wasps). Patients with a predisposition to allergic reactions during desensitizing therapy should use ACE inhibitors with caution. Do not administer ACE inhibitors to patients receiving immunotherapy with bee venom. Nevertheless, this reaction can be avoided by the temporary withdrawal of the ACE inhibitor before the procedure begins.

Liver failure

In rare cases, the administration of ACE inhibitors is associated with a syndrome that begins with the development of cholestatic jaundice, progressing to fulminant liver necrosis, 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 in patients receiving ACE inhibitors, perindopril therapy should be discontinued and appropriate medical examination performed.

Neutropenia / agranulocytosis / thrombocytopenia / anemia

Neutropenia, agranulocytosis, thrombocytopenia and anemia can develop against the background of therapy with ACE inhibitors.In patients with normal renal function, in the absence of obvious violations of the function of other organs, neutropenia occurs rarely. With extreme caution follow the apply perindopril in patients with systemic connective tissue diseases, with immunosuppressant, allopurinol or procainamide, especially in patients with impaired renal function. There is a risk of developing severe infectious diseases resistant to intensive antibiotic therapy. In treating perindopril patients with the above factors, it is necessary to regularly monitor the number of white blood cells and warn the patient about the need to inform the doctor about any symptoms of infection (eg, sore throat, fever).

Ethnic differences

It is necessary to take into account a higher risk of developing angioedema in patients of the Negroid race. Like other ACE inhibitors, perindopril may be less effective in reducing blood pressure in patients of the Negroid race. This fact, in all probability, is associated with a higher prevalence of low-grade status in the population of patients of the Negroid race with arterial hypertension.

Cough

Against the background of therapy with an ACE inhibitor, a persistent, dry, unproductive cough may occur, which ceases after the withdrawal of perindopril. This should be taken into account in the differential diagnosis of cough.

Surgery / general anesthesia

The use of ACE inhibitors in patients undergoing extensive surgical intervention and / or general anesthesia can lead to the development of arterial hypotension or collapse, which is due to a sharp increase in antihypertensive action. Admission perindoprila should be discontinued one day before surgery. With the development of arterial hypotension, measures should be taken to replenish the volume of circulating blood. It is necessary to alert the surgeon / anesthesiologist that the patient is taking ACE inhibitors.

Hyperkalemia

During treatment with ACE inhibitors, including perindopril, hyperkalemia may develop. Risk factors for hyperkalemia include renal failure, decreased renal function, age over 70 years, diabetes mellitus, certain concomitant conditions (dehydration, acute heart failure, metabolic acidosis),simultaneous intake of potassium-sparing diuretics (such as spironolactone and its derivative eplerenone, triamterene, amiloride), food additives / potassium preparations or potassium-containing substitutes for edible salt, as well as the use of other drugs that increase the potassium content in the blood (for example, heparin). The use of dietary supplements / potassium preparations, potassium-sparing diuretics, potassium-containing substitutes for edible salt can lead to a significant increase in potassium in the blood, especially in patients with reduced renal function. Hyperkalemia can lead to serious, sometimes fatal heart rhythm disturbances. If simultaneous administration of perindopril and the above drugs is required, treatment should be carried out with caution in the context of regular monitoring of potassium in the blood serum (see section "Interaction with other drugs").

Patients with diabetes mellitus

In patients taking hypoglycemic agents for ingestion or insulin, during the first month of therapy with ACE inhibitors, the concentration of glucose in the blood should be carefully monitored.

Lithium preparations

It is not recommended to use lithium preparations together with perindopril.

Potassium-sparing diuretics, potassium preparations, potassium-containing products and nutritional supplements

It is not recommended simultaneous use of perindopril and potassium-sparing diuretics, as well as potassium, potassium-containing substitutes for edible salt and food additives (see section "Interaction with other drugs").

Double blockade of RAAS

Arterial hypotension, fainting, stroke, hyperkalemia and renal dysfunction (including acute renal failure) have been reported in susceptible patients, especially when used with medications that affect this system. Therefore, a double blockade of RAAS due to a combination of an ACE inhibitor with ARA II or aliskiren is not recommended. Simultaneous use with aliskiren is contraindicated in patients with diabetes mellitus or renal dysfunction (GFR <60 mL / min / 1.73 m² body surface area) (see the sections "Contraindications" and "Interaction with other medicinal products"). It is not recommended simultaneous use of ACE inhibitors with APA II in patients with diabetic nephropathy.

Amlodipine

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

In studies in vitro Amlodipine does not affect the binding of blood proteins to digoxin, phenytoin, warfarin and indomethacin.

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 functional class by classification NYHA non-ischemic origin, there was an increase in the incidence of pulmonary edema, despite the absence of signs of worsening heart failure.

In patients with impaired hepatic function T_1/2and AUC Amlodipine increases. Admission of amlodipine should start with the lowest doses and observe precautions, both at the beginning of treatment, and with increasing doses. Patients with severe hepatic insufficiency should increase the dose gradually, ensuring thorough monitoring of the clinical condition.

In elderly patients, T can increase_1/2and decrease the clearance of amlodipine. Dose changes are not required, but more careful monitoring of patients of this category is necessary.

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

Although Amlopress® has not been shown to have any adverse effects on the ability to drive vehicles or other mechanisms, however, due to the possible pronounced reduction in blood pressure, development of dizziness and drowsiness, caution should be exercised, especially at the beginning of therapy and with increasing doses.

Form release / dosage:Tablets, 5 mg + 4 mg, 5 mg + 8 mg, 10 mg + 4 mg and 10 mg + 8 mg.

Packaging:

For 10 tablets in a blister of PA / Al / PVC-aluminum foil.

For 3 blisters in a cardboard box together with instructions for use.

Storage conditions:

Store in a dry, dark place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-003694

Date of registration:21.06.2016

Expiration Date:21.06.2021

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

Manufacturer: & nbsp

GEDEON RICHTER POLAND, Co. Ltd. Poland

Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary

Information update date: & nbsp25.07.2017

Illustrated instructions

Instructions

Amlopress® (Amlopress®)