Egipres caps 5mg + 10mg #30

Egipres instruction

You can buy Egipres here

Composition

amlodipine besylate 6.95 / 6.95 / 13.9 / 13.9 mg (corresponding to amlodipine - 5/5/10/10 mg)
ramipril 5/10/5/10 mg
excipients: crospovidone - 20/40/40/40 mg; hypromellose - 1.18 / 2.36 / 2.36 / 2.36 mg; MCC - 114.82 / 229.64 / 229.64 / 229.64 mg; glyceryl dibegenat - 2.05 / 4.1 / 4.1 / 4.1 mg
Capsules, 5 mg + 5 mg; hard gelatin capsule (CONI-SNAP 3), color code of the cover and base - 51072: brilliant blue dye (E133), charming red dye (E129), titanium dioxide, gelatin.
Capsules, 5 mg + 10 mg; hard gelatin capsule (CONI-SNAP 0), color code of the cover and base - 51072/37350: cover - titanium dioxide; brilliant blue dye (E133), charming red dye (E129); gelatin; base - titanium dioxide; iron dye red oxide (E172); gelatin.
Capsules, 10 mg + 5 mg; hard gelatin capsule (CONI-SNAP 0), color code of the cover and base - 33007/37350: cover - titanium dioxide; dye azorubine (E122); Indigo Carmine (E132); gelatin; base - titanium dioxide; iron dye red oxide (E172); gelatin.
Capsules, 10 mg + 10 mg; hard gelatin capsule (CONI-SNAP 0), color code of the cover and base - 33007: dye azorubine (E122), indigo carmine (E132), titanium dioxide, gelatin.

Description of the dosage form

Capsules 5 mg + 5 mg: solid gelatin CONI-SNAP 3, self-closing, with a base and a lid of light burgundy color.
Capsules 5 mg + 10 mg: solid gelatin CONI-SNAP 0, self-closing, with a light pink base and a light burgundy cap.
Capsules 10 mg + 5 mg: solid gelatin CONI-SNAP 0, self-closing, with a light pink base and a maroon cap.
Capsules 10 mg + 10 mg: hard gelatin capsules CONI-SNAP 0, self-closing, with a maroon base and lid.
Capsule contents: a mixture of granules and powders of white or almost white color, without or almost odorless.
Pharmacological action - antihypertensive.

Pharmacodynamics

Amlodipine

Derivative of dihydropyridine. By binding to dihydropyridine receptors, it blocks slow calcium channels, inhibits the transmembrane transition of calcium into the cells of vascular smooth muscle and the heart (to a greater extent - into vascular smooth muscle cells than into cardiomyocytes). It has antihypertensive and antianginal effects.

The mechanism of antihypertensive action of amlodipine is due to a direct relaxing effect on vascular smooth muscle.

Amlodipine reduces myocardial ischemia in the following two ways:

1. Expands peripheral arterioles and thus reduces the round focal disease (afterload), while the heart rate remains almost unchanged, which leads to a decrease in energy consumption and myocardial oxygen demand.

2. It expands the coronary and peripheral arteries and arterioles in both normal and ischemic areas of the myocardium, which increases the oxygen supply to the myocardium in patients with vasospastic angina (Prinzmetal angina) and prevents the development of coronary spasm caused by smoking.

In patients with arterial hypertension (AH), the daily dose of amlodipine provides a decrease in blood pressure for 24 hours (both in the supine position and standing). Due to the slow onset of action, amlodipine does not cause a sharp decrease in blood pressure.

In patients with angina, a single daily dose of Egipres increases the duration of exercise, retards the development of another attack of angina pectoris and depression of the ST segment (1 mm) against the background of exercise, reduces the frequency of strokes and the need for nitroglycerin.

The use of amlodipine in patients with coronary artery disease. In patients with cardiovascular disease (including coronary atherosclerosis with lesions from one vessel and up to stenosis of 3 or more arteries and atherosclerosis of the carotid arteries) who have had a myocardial infarction (MI), percutaneous transluminal angioplasty of the coronary arteries (TLP) or stenocardia, use the use of the coronary arteries (TLP) or the use of stenocardia, use of the stenocardial arteries, suffering from stenocardial arteriosclerosis of the coronary artery development of carotid intimal media thickening, significantly reduces mortality from cardiovascular causes, myocardial infarction, stroke, TLP, aorto-coronary bypass, leads to a decrease in the number of hospitalizations for not tabilnoy angina and progression of heart failure, reduces the frequency of interventions aimed at restoring coronary blood flow.
The use of amlodipine in patients with heart failure (HF). Amlodipine does not increase the risk of death or the development of complications and deaths in patients with CHF III – IV functional class (FC) according to the classification of the New York Heart Association (NYHA) during therapy with digoxin, diuretics and ACE inhibitors. Patients with CHF III – IV FC according to NYHA of non-ischemic etiology when using amlodipine, there is a likelihood of pulmonary edema. Amlodipine does not cause adverse metabolic effects, including it does not affect lipid profile.

Ramipril

Ramiprilat, which is formed with the participation of liver enzymes, the active metabolite of ramipril, is a long-acting inhibitor of the enzyme dipeptidylcarboxypeptidase I (synonyms - ACE, kininase II). In blood plasma and tissues, this enzyme kininase II catalyzes the conversion of angiotensin I into the active vasoconstrictor, angiotensin II, and also promotes the breakdown of bradykinin. Reduced formation of angiotensin II and inhibition of the breakdown of bradykinin leads to vasodilatation and lower blood pressure. The increased activity of the kallikrein-kinin system in the blood and tissues causes the cardioprotective and endothelioprotective effect of ramipril due to the activation of the PG-system and, accordingly, an increase in the synthesis of PG, stimulating the formation of nitric oxide (NO) in endotheliocytes. Angiotensin II stimulates the production of aldosterone, so taking ramipril reduces aldosterone secretion and increases the content of potassium ions in serum.

By reducing the content of angiotensin II in the blood, its inhibitory effect on renin secretion by the type of negative feedback is eliminated, which leads to an increase in plasma renin activity.

It is assumed that the development of some undesirable reactions (in particular, dry cough) is associated with an increase in the activity of bradykinin.

In patients with hypertension, taking ramipril leads to a decrease in blood pressure in the supine position and standing, without a compensatory increase in heart rate. Ramipril significantly reduces OPSS, almost without causing changes in the renal blood flow and glomerular filtration rate. The antihypertensive effect begins to appear after 1-2 hours after ingesting a single dose of Egipres, reaching its highest value after 3-6 hours, and lasts for 24 hours. When taking an exchange dose, the antihypertensive effect can gradually increase, stabilizing usually by 3-4 weeks regular use of Egipres and then persisting for a long time. Sudden discontinuation of the drug does not lead to a rapid and significant increase in blood pressure (no withdrawal syndrome).

In patients with hypertension, ramipril slows down the development and progression of myocardial hypertrophy and vascular wall.

In patients with CHF, ramipril reduces round focal disease (decreased afterload on the heart), increases the capacity of the venous bed and decreases the filling pressure of the left ventricle (LV), which consequently leads to a decrease in the preload on the heart. In these patients, when receiving ramipril, there is an increase in cardiac output, ejection fraction, and improvement in exercise tolerance.

In diabetic and non-diabetic nephropathy, ramipril intake slows down the rate of progression of renal failure and the onset of end-stage renal failure and thereby reduces the need for hemodialysis procedures or kidney transplantation. In the initial stages of diabetic or non-diabetic nephropathy, ramipril reduces the severity of albuminuria.
In patients with a high risk of developing cardiovascular disease due to the presence of vascular lesions (diagnosed ischemic heart disease, a history of obliterating peripheral artery disease, a history of stroke) or diabetes mellitus with at least one additional risk factor (microalbuminuria, AH, increased total cholesterol, reduced levels HDL cholesterol, smoking) adding ramipril to standard therapy significantly reduces the incidence of myocardial infarction, stroke and cardiovascular mortality.

In addition, ramipril reduces overall mortality, as well as the need for revascularization procedures, slowing the occurrence or progression of CHF.

In patients with HF that developed in the first days of acute MI (AMI) (2–9 days), when taking ramipril, starting from day 3 to day 10 of AMI, the risk of mortality decreases (by 27%), the risk sudden death (by 30%), risk of CHF progression to severe - NYHA FC III – IV resistant to therapy (by 27%), probability of subsequent hospitalization due to the development of HF (by 26%). In the general population of patients, as well as in patients with diabetes mellitus, both with hypertension and with normal blood pressure, ramipril significantly reduces the risk of nephropathy and the occurrence of microalbuminuria.

Pharmacokinetics

Amlodipine

After ingestion in therapeutic doses, amlodipine is well absorbed, the time to reach Cmax in the blood plasma when administered orally is 6–12 hours. Absolute bioavailability is 64–80%. Vd is approximately 21 L / kg. Communication with proteins of a blood plasma makes about 97,5%. Food intake does not affect the absorption of amlodipine. Egipres penetrates through the BBB.

T1 / 2 of blood plasma is about 35-50 hours, which corresponds to the purpose of Egipres 1 time per day. In patients with liver failure and severe CHF, T1 / 2 increases to 56–60 h.

Overall clearance - 0.43 l / h / kg.

Stable Css (5–15 ng / ml) is reached after 7–8 days of continuous administration of amlodipine, it is metabolized in the liver to form inactive metabolites. 10% of the original drug and 60% of the metabolites excreted by the kidneys, and 20% through the intestines. Withdrawal from breast milk is unknown. Amlodipine is not removed during hemodialysis.

Special patient groups

Renal failure. T1 / 2 from blood plasma in patients with renal insufficiency is increased to 60 hours. The change in the concentration of amlodipine in the blood plasma does not correlate with the degree of renal dysfunction.

Elderly patients. The time to reach Сmax and Сmax of amlodipine practically does not differ from those in younger patients. In elderly patients suffering from CHF, there was a tendency to a decrease in the clearance of amlodipine, which leads to an increase in AUC and T1 / 2 to 65 hours.

Ramipril

After ingestion, it is rapidly absorbed from the gastrointestinal tract (50–60%). Meal slows down its absorption, but does not affect the degree of absorption. Ramipril is subjected to intensive presystemic metabolism / activation (mainly in the liver, by hydrolysis), as a result of which its only active metabolite is formed - ramiprilat, whose activity in relation to ACE inhibition is about 6 times higher than the activity of ramipril. In addition, as a result of ramipril metabolism, diketopiperazine, which does not possess pharmacological activity, is formed, which then undergoes conjugation with glucuronic acid. Ramiprilat is also glucuronated and metabolized to diketopiperazinic acid. The bioavailability of ramipril after oral administration ranges from 15% (for a dose of 2.5 mg) to 28% (for a dose of 5 mg). The bioavailability of ramiprilat after oral administration of 5 mg of ramipril is approximately 45% (compared to its bioavailability after intravenous administration in the same doses).
After taking ramipril inside, the time to reach Cmax of ramipril and ramiprilat is 1 and 2-4 hours, respectively. The decrease in plasma concentration of ramiprilat occurs in several stages: the distribution and elimination phase with T1 / 2 ramiprilat of approximately 3 hours, then the intermediate phase with T1 / 2 of ramiprilat of approximately 15 hours, and the final phase with a very low concentration of ramiprilat blood plasma and a T1 / 2 ramiprilat of approximately 4–5 days. This final phase is due to the slow release of ramiprilat from a strong bond with the ACE receptors. Despite the prolonged final phase with a single dose of ramipril orally during the day at a dose of 2.5 mg or more, the Css of ramiprilat is reached after approximately 4 days of treatment. In the course of administration of Egipres effective T1 / 2 (depending on the dose) is 13-17 hours.

Plasma protein binding is approximately 73% for ramipril and 56% for ramiprilat.

After the on / in the introduction of Vd ramipril and ramiprilat are approximately 90 and 500 liters, respectively.

After ingestion of ramipril, labeled with a radioactive isotope (10 mg), 39% of the radioactivity is excreted through the intestines and about 60% by the kidneys. After iv administration of ramipril, 50–60% of the dose is detected in the urine as ramipril and its metabolites. After iv administration of ramiprilat, about 70% of the dose is found in the urine as ramiprilat and its metabolites, in other words, when iv administration of ramipril and ramiprilat, a significant portion of the dose is eliminated through the intestine with bile, bypassing the kidneys (50 and 30%, respectively) . After ingestion of 5 mg of ramipril in patients with drainage of the bile ducts, almost the same amount of ramipril and its metabolites are excreted by the kidneys and through the intestines during the first 24 hours after ingestion.

Approximately 80–90% of metabolites in urine and bile were identified as ramiprilat and ramiprilat metabolites. Ramipril glucuronide and ramipril diketopiperazin account for approximately 10–20% of the total, while the content of unmetabolized ramipril in the urine is approximately 2%.

In cases of impaired renal function with Cl of creatinine less than 60 ml / min, the excretion of ramiprilat and its metabolites by the kidneys slows down. This leads to an increase in plasma ramiprilat concentration, which decreases more slowly than in patients with normal renal function. When you take ramipril in high doses (10 mg), an abnormal liver function leads to a slower presystemic metabolism of ramipril to active ramiprilat and a slower elimination of ramiprilat. In healthy volunteers and patients with hypertension after 2 weeks of ramipril treatment in a daily dose of 5 mg, there is no clinically significant accumulation of ramipril and ramiprilat. In patients with CHF, after 2 weeks of ramipril treatment in a daily dose of 5 mg, there is an increase of 1.5-1.8 times the concentration of ramiprilat in the blood plasma and AUC.

In healthy elderly volunteers (65–76 years), the pharmacokinetics of ramipril and ramiprilat are not significantly different from those in young healthy volunteers.

Indications of the drug Egipres

Arterial hypertension (patients who have shown combination therapy with amlodipine and ramipril in doses, as in combination).

Contraindications for Egipres

Amlodipine

hypersensitivity to amlodipine and other dihydropyridine derivatives;
severe hypotension (SAD less than 90 mmHg), shock (including cardiogenic);
an obstructive process that impedes the release of blood from the left ventricle (for example, clinically significant aortic stenosis);
hemodynamically unstable heart failure after myocardial infarction;
pregnancy;
breastfeeding period;
age up to 18 years (safety and efficacy not determined).

Ramipril

hypersensitivity to ramipril and other ACE inhibitors;
history of angioedema (hereditary or idiopathic, as well as associated with previous therapy with ACE inhibitors);
hemodynamically significant renal artery stenosis (bilateral or unilateral, in the case of a single kidney);
arterial hypotension (SAD less than 90 mmHg) or conditions with unstable hemodynamic parameters;
hemodynamically significant aortic or mitral valve stenosis or hypertrophic obstructive cardiomyopathy;
primary hyper aldosteronism;
severe renal impairment (Cl creatinine <20 ml / min / 1.73 m2);
hemodialysis (experience with clinical use is insufficient);
nephropathy, the treatment of which is carried out by the SCS, NSAIDs, immunomodulators and / or other cytotoxic agents (clinical experience is insufficient);
decompensated chronic heart failure (experience with clinical use is insufficient);
hemodialysis or hemofiltration using certain types of membranes with a negatively charged surface, such as high-flow polyacrylonitrile membranes (risk of hypersensitivity reactions);
LDL apheresis using dextran sulfate (risk of hypersensitivity reactions);
desensitization therapy in case of hypersensitivity reactions to the poisons of insects - bees, wasps;
acute stage of myocardial infarction in patients with diseases such as severe heart failure (NYHA functional class IV); life-threatening ventricular arrhythmias; pulmonary heart;
simultaneous use of drugs containing aliskiren in patients with impaired renal function (Cl creatinine less than 60 ml / min) and patients with diabetes mellitus;
pregnancy;
breastfeeding period;
age up to 18 years (experience of clinical use is insufficient).

Amlodipine + ramipril

hypersensitivity to excipients that are part of Egipres;
renal insufficiency (Cl creatinine <20 ml / min / 1.73 m2);
pregnancy;
breastfeeding period;
age up to 18 years (experience of clinical use is insufficient).

With caution for the combination of amlodipine + ramipril: atherosclerotic lesions of the coronary and cerebral arteries (the danger of an excessive decrease in blood pressure); increased activity of the RAAS, in which with the inhibition of ACE there is a risk of a sharp decrease in blood pressure with deterioration of renal function; severe, especially malignant hypertension; CHF, especially severe or about which other drugs with antihypertensive action are taken; hemodynamically significant unilateral renal artery stenosis (in the presence of both kidneys); prior diuretic administration; violations of water and electrolyte balance, reduction of bcc (including while taking diuretics, salt-free diets, diarrhea, vomiting, excessive sweating); simultaneous use with drugs containing aliskiren (with double blockade of RAAS increases the risk of a sharp decrease in blood pressure, hyperkalemia and deterioration of renal function); abnormal liver function (lack of experience with application: both strengthening and weakening of the effects of ramipril is possible; in patients with cirrhosis of the liver with ascites and edema, a significant activation of the RAAS is possible); impaired renal function (Cl creatinine more than 20 ml / min); condition after kidney transplantation; Systemic diseases of the connective tissue, incl. systemic lupus erythematosus, scleroderma, concomitant therapy with drugs that can cause changes in the pattern of peripheral blood (including allopurinol, procainamide) - possibly inhibition of bone marrow hematopoiesis, development of neutropenia or agranulocytosis; diabetes mellitus (risk of developing hyperkalemia); advanced age (risk of increased antihypertensive effect); hyperkalemia; hyponatremia; CHF of non-ischemic etiology of III – IV functional class according to NYHA classification; aortic stenosis; sick sinus syndrome; mitral stenosis; hypotension; the only functioning kidney; renovascular hypertension; simultaneous use of dantrolene, estramustine, potassium-saving diuretics and potassium preparations, potassium-containing food salt substitutes, lithium preparations; surgery / general anesthesia; hemodialysis using high-flow membranes (for example AN69®).

Use during pregnancy and lactation

Egipres is contraindicated for use, because ramipril can have an adverse effect on the fetus - impaired development of the kidneys of the fetus, lowering blood pressure of the fetus and newborns, impaired renal function, hyperkalemia, hypoplasia of the skull bones, oligohydramnios, contracture of the extremities, deformation of the bones of the skull, hypoplasia of the lungs. Before starting Egipres in women of childbearing age, pregnancy should be excluded.

If a woman is planning a pregnancy, treatment with Egipres should be discontinued. If pregnancy occurs during drug treatment, it should be discontinued as soon as possible and the patient transferred to other drugs, the application of which will have the lowest risk for the child.

If drug treatment is necessary during breastfeeding, it should be discontinued (data on the elimination of amlodipine and ramipril with breast milk of women are not available).

Fertility

Amlodipine. In some patients receiving BPC, reversible biochemical changes were observed in the sperm heads. Clinical data are insufficient to assess the potential effect of amlodipine on fertility.

Side effects of Egipres

The undesirable effects listed below are given in accordance with the following gradations of the frequency of their occurrence according to the WHO classification: very often - more than 1/10 (more than 10%); often - more than 1/100, but less than 1/10 (more than 1%, but less than 10%); infrequently - more than 1/1000, but less than 1/100 (more than 0.1%, but less than 1%); rarely, more than 1/10000, but less than 1/1000 (more than 0.01%, but less than 0.1%); very rarely - less than 1/10000 (less than 0.01%).

Amlodipine

On the part of the cardiovascular system: often - peripheral edema (ankles and feet), a feeling of heartbeat; infrequently - excessive decrease in blood pressure, orthostatic hypotension, vasculitis; rarely, development or worsening of HF; very rarely - cardiac arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), MI, chest pain, migraine.

On the part of the musculoskeletal system and connective tissue: infrequently - arthralgia, muscle cramps, myalgia, back pain, arthrosis; rarely - myasthenia.

From the side of the central nervous system and peripheral nervous system: often - a sensation of heat and flushing of the skin of the face, increased fatigue, dizziness, headache, drowsiness; infrequently - indisposition, fainting, increased sweating, asthenia, hypesthesia, paresthesia, peripheral neuropathy, tremor, insomnia, mood lability, unusual dreams, nervousness, depression, anxiety; rarely - convulsions, apathy; very rarely - ataxia, amnesia, isolated cases of extrapyramidal syndrome.

On the part of the digestive system: often - abdominal pain, nausea; infrequently - vomiting, changes in the mode of bowel movement (including constipation, flatulence), dyspepsia, diarrhea, anorexia, dryness of the oral mucosa, thirst; rarely - gingival hyperplasia, increased appetite; very rarely - gastritis, pancreatitis, hyperbilirubinemia, jaundice (usually cholestatic), increased activity of hepatic transaminases, hepatitis.

From the side of blood: very rarely - thrombocytopenic purpura, thrombocytopenia, leukopenia.

Metabolic disorders: very rarely - hyperglycemia.

On the part of the respiratory system: infrequently - shortness of breath, rhinitis; very rarely - cough.

On the part of the kidneys and urinary tract: infrequently - frequent urination, painful urination, nocturia, impotence; very rarely - dysuria, polyuria.

Allergic reactions: infrequently - skin itch, rash; very rarely - angioedema, erythema multiforme, urticaria.

Others: infrequently - alopecia, tinnitus, gynecomastia, weight gain / loss, visual impairment, diplopia, accommodation disturbance, xerophthalmia, conjunctivitis, eye pain, taste perversion, chills, nose bleeding; rarely - dermatitis; very rarely - parosmia, xerodermia, cold sweat, impaired skin pigmentation.

Ramipril

From the side of the heart: infrequently - myocardial ischemia, including the development of an attack of stenocardia or myocardial infarction, tachycardia, arrhythmias (appearance or intensification), palpitations, peripheral edema.

On the part of the vessels: often - excessive reduction of blood pressure, impaired orthostatic regulation of vascular tone (orthostatic hypotension), syncopal states; infrequently - flushing of the skin of the face; rarely - the occurrence or enhancement of circulatory disorders on the background of stenotic vascular lesions, vasculitis; frequency is unknown - Raynaud's syndrome.

From the side of the central nervous system: often - headache, a feeling of lightness in the head; infrequently - dizziness, agevziya (loss of taste sensitivity), dysgeusia (violation of taste sensitivity), paresthesia (burning sensation); rarely - tremor, imbalance; frequency unknown - cerebral ischemia, including ischemic stroke and transient violation of cerebral circulation, impaired psychomotor reactions, parosmia (disturbance of perception of smells).

On the part of the organ of vision: infrequently - visual impairment, including blurred vision; rarely - conjunctivitis.

On the part of the organ of hearing: rarely - hearing loss, ringing in the ears.

On the part of the psyche: infrequently - depressed mood, anxiety, nervousness, restlessness, sleep disturbances, including drowsiness; rarely - confusion; frequency unknown - impaired concentration.

On the part of the respiratory system: often - dry cough (worse at night and when lying down), bronchitis, sinusitis, shortness of breath; infrequently - bronchospasm, including worsening of the course of bronchial asthma, nasal congestion.

On the part of the digestive system: often - inflammatory reactions in the stomach and intestines, digestive disorders, discomfort in the abdomen, dyspepsia, diarrhea, nausea, vomiting; Infrequently - pancreatitis, incl. and fatal (cases of pancreatitis with a fatal outcome when taking ACE inhibitors were extremely rare), increased activity of pancreatic enzymes in the blood plasma, intestinal angioedema, edema, gastritis, constipation, dry oral mucosa; rarely - glossitis; unknown frequency - aphthous stomatitis (inflammatory reaction of the oral mucosa).

On the part of the hepatobiliary system: infrequently - increased activity of liver enzymes and the content of conjugated bilirubin in the blood plasma; rarely - cholestatic jaundice, hepatocellular lesions; unknown frequency - acute liver failure, cholestatic or cytolytic hepatitis (death was extremely rare).

On the part of the kidneys and urinary tract: infrequently - impaired renal function, including the development of acute renal failure, an increase in the excretion of urine, an increase in pre-existing proteinuria, an increase in the concentration of urea and creatinine in the blood.

On the part of the reproductive system and mammary glands: infrequently - transient impotence due to erectile dysfunction, decreased libido; frequency unknown - gynecomastia.

From the side of blood and lymphatic system: infrequently - eosinophilia; rarely - leukopenia, including neutropenia and agranulocytosis, a decrease in the number of erythrocytes in peripheral blood, a decrease in hemoglobin, thrombocytopenia; frequency is unknown - oppression of bone marrow hematopoiesis, pancytopenia, hemolytic anemia.

On the part of the skin and mucous membranes: often - skin rash, in particular maculopapular; infrequently - angioedema, incl. and fatal (laryngeal edema can cause airway obstruction, resulting in death), pruritus, hyperhidrosis (sweating); rarely - exfoliative dermatitis, urticaria, onycholysis; very rarely - photosensitivity reactions; unknown frequency - toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, worsening of the course of psoriasis, psoriasis-like dermatitis, pemphigoid or lichenoid (desiccous) exanthema or enanthema, alopecia.

From the musculoskeletal system and connective tissue: often - muscle cramps, myalgia; infrequently - arthralgia.

On the part of metabolism, nutrition and laboratory parameters: often - an increase in the content of potassium in the blood; infrequently - anorexia, loss of appetite; frequency unknown - decrease in sodium concentration in the blood, syndrome of inadequate secretion of ADH.

On the part of the immune system: the frequency is unknown - anaphylactic or anaphylactoid reactions (with inhibition of ACE, the number of anaphylactic or anaphylactoid reactions to insect poisons increases), an increase in the titer of antinuclear antibodies.

General disorders: often - chest pain, feeling tired; infrequently - fever; rarely - asthenia (weakness).

Interaction

Amlodipine

Inhibitors of microsomal liver oxidation enzymes (erythromycin in young people, diltiazem in the elderly, ketoconazole, itraconazole, ritonavir) can be expected to increase the concentration of amlodipine in the blood plasma, increasing the risk of side effects, and inductors of microsomal oxidation enzymes of the liver decrease. With simultaneous use of amlodipine with cimetidine, the pharmacokinetics of amlodipine does not change.

The simultaneous single dose of 240 ml of grapefruit juice and 10 mg of amlodipine orally is not accompanied by a significant change in the pharmacokinetics of amlodipine. Unlike other BPCs, the clinically significant interaction of amlodipine (III generation BPC) was not found when used together with NSAIDs, especially indomethacin.

It is possible to enhance the antianginal and antihypertensive effects of BPC when used together with thiazide and loop diuretics, verapamil, ACE inhibitors, beta-blockers and nitrates, as well as increase their anti-hypertensive effect when used together with alpha1-blockers, neuroleptics. Although in the study of amlodipine negative inotropic effect is usually not observed, however, some CCBs may increase the severity of the negative inotropic effect of antiarrhythmic drugs causing prolongation of the QT interval (for example, amiodarone and quinidine).

The combined use of BPC with lithium preparations (for amlodipine data are not available) may increase the manifestation of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

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

A single dose of aluminum / magnesium-containing antacids has no significant effect on the pharmacokinetics of amlodipine.

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

Repeated use 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. With simultaneous use of amlodipine with digoxin in healthy volunteers, the content of digoxin in serum and its renal clearance do not change. With a single and repeated use at a dose of 10 mg, amlodipine does not have a significant effect on the pharmacokinetics of ethanol.

Amlodipine does not affect the change in PV caused by warfarin. Amlodipine does not cause significant changes in the pharmacokinetics of cyclosporine.

Combinations not recommended

The simultaneous use of dantrolene (w / administration), inductors isoenzyme cytochrome CYP3A4 (e.g. rifampicin, drugs Hypericum perforatum) and inhibitors isoenzyme cytochrome CYP3A4 (protease inhibitors, antifungals group azoles, macrolides (such as erythromycin, or clarithromycin), verapamil or diltiazem) .

Ramipril

The use of some high-flow membranes with a negatively charged surface (for example, polyacrylonitrile membranes) during hemodialysis or hemofiltration; The use of dextran sulfate in LDL apheresis is the risk of developing severe anaphylactic reactions.

Combinations not recommended

With potassium salts, potassium-sparing diuretics (for example amiloride, triamterene, spironolactone) and other drugs, including with antagonists of angiotensin II receptors (APA II), trimethoprim, tacrolimus, cyclosporine — hyperkalemia may develop (if used simultaneously, regular monitoring of serum potassium is required).

Combinations that should be used with caution

With antihypertensive drugs (especially diuretics) and other drugs that reduce blood pressure (nitrates, tricyclic antidepressants, general and local anesthesia, ethanol, baclofen, alfuzosin, doxazosin, prazosin, tamsulosin, terazosin) - potentiation of antihypertensive effect. When combined with diuretics, serum sodium should be monitored.

With sleeping pills, narcotic and other painkillers - a more pronounced decrease in blood pressure is possible.

With vasopressor sympathomimetics (epinephrine, isoproterenol, dobutamine, dopamine) - reducing the antihypertensive effect of ramipril, requires regular monitoring of blood pressure.

With allopurinol, procainamide, cytostatics, immunosuppressants, systemic corticosteroids and other means that may affect hematological parameters, combined use increases the risk of leukopenia.

With lithium salts, an increase in serum lithium and an increase in the cardio and neurotoxic effects of lithium.

With oral hypoglycemic agents (sulfonylurea derivatives, biguanides), insulin - due to a decrease in insulin resistance under the influence of ramipril, the hypoglycemic effect of these drugs may increase, up to the development of hypoglycemia.

The simultaneous use of drugs containing aliskiren in patients with diabetes and renal insufficiency (Cl creatinine less than 60 ml / min), as well as vildagliptin - due to an increase in the incidence of angioedema and simultaneous use with ACE inhibitors.

Combinations to be taken into account

With NSAIDs (indomethacin, acetylsalicylic acid) - it is possible to weaken the effect of ramipril, increase the risk of renal dysfunction and increase the content of potassium in the blood serum.

With heparin, an increase in serum potassium is possible.

With sodium chloride, a weakening of the antihypertensive effect of ramipril and a less effective treatment of the symptoms of CHF.

With ethanol - increased vasodilation symptoms. Ramipril may increase the adverse effects of ethanol on the body.

With estrogen - a weakening of the antihypertensive effect of ramipril (fluid retention).

Desensitizing therapy for hypersensitivity to the poisons of insects - ACE inhibitors, including ramipril, increase the likelihood of severe anaphylactic or anaphylactoid reactions to insect poisons.

Dosage and administration

Inside, 1 caps. Once a day, at the same time, regardless of the meal.

The dose of Egipres is selected after a previous titration of doses of individual components of Egipres: ramipril and amlodipine in patients with hypertension. The drug Egipres with fixed doses of active ingredients cannot be used for initial therapy. If patients need a dose adjustment, then it should be carried out only by titrating the doses of the active components in monotherapy. Only after that it is possible to use the drug Egipres with fixed doses of the active components in the combinations below.

With therapeutic necessity, the dose of Egipres can be changed based on individual titration of the doses of individual components: 5 mg of amlodipine + 5 mg of ramipril or 5 mg of amlodipine + 10 mg of ramipril or 10 mg of amlodipine + 5 mg of ramipril or 10 mg of amlodipine + 10 mg of ramipril.

Egipres in a dose of 10 mg of amlodipine + 10 mg of ramipril is the maximum daily dose of Egipres, which is not recommended to exceed. Dosages of 10 mg of amlodipine + 5 mg of ramipril (for amlodipine) and 5 mg of amlodipine + 10 mg of ramipril (for ramipril) are the maximum daily doses.

Adult patients

In patients taking diuretics, Egipres should be prescribed with caution, due to the risk of impaired water and electrolyte balance. In these patients, kidney function and potassium should be monitored.

Patients of advanced age and patients with a renal failure. Removal of amlodipine and ramipril and its metabolites in elderly patients and patients with renal insufficiency is slowed down. Therefore, in these patients it is necessary to regularly monitor the content of creatinine and potassium in the blood plasma. Egipres may be administered to patients with creatinine Cl equal to or greater than 60 ml / min. With Cl creatinine <60 ml / min, as well as in patients with hypertension on hemodialysis, Egipres is recommended only for patients who received 5 mg of ramipril as the optimal maintenance dose during the individual dose titration process. There is no need to titrate an individual dose of amlodipine in patients with impaired renal function. Egipres is contraindicated in patients with creatinine Cl <20 ml / min / 1.73 m2. Changes in the concentration of amlodipine in the blood plasma do not correlate with the severity of renal failure.

Patients with liver failure. Care should be taken when prescribing Egipres to patients with hepatic insufficiency due to the lack of recommendations on the dosage of the drug in these patients. Egipres is recommended only for patients who received 2.5 mg of ramipril as the optimal maintenance dose during the individual dose titration process.

Kids and teens

Egipres should not be prescribed to children and adolescents under 18 years of age due to the lack of data on the efficacy and safety of the use of ramipril and amlodipine in these groups of patients both as monotherapy and as a combination therapy.

Overdose

Information about overdose of the drug Egipres is missing.

Amlodipine

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

Treatment: the appointment of activated carbon (especially in the first 2 hours after overdose), gastric lavage, impart an elevated position to the extremities, actively maintaining the functions of the CAS, monitoring the performance of the heart and lungs, monitoring of BCC and diuresis. To restore vascular tone and blood pressure, if there are no contraindications, it may be useful to use vasoconstrictor drugs. Use in / in the introduction of calcium gluconate. Amlodipine largely binds to serum proteins, so hemodialysis is ineffective.

Ramipril

Symptoms: excessive peripheral vasodilation with the development of pronounced decrease in blood pressure, shock; bradycardia or reflex tachycardia, water and electrolyte disorders, acute renal failure, stupor.

Treatment: gastric lavage, the appointment of adsorbents, sodium sulfate (if possible during the first 30 minutes). In the case of a pronounced decrease in the patient's blood pressure, the patient should be laid, the legs should be raised, and the functions of the cardiovascular system should be actively maintained additionally, the administration of alpha1-adrenergic agonists (norepinephrine, dopamine) and angiotensin-amide can be added to therapy for replenishing bcc and restoring electrolyte balance. In the case of bradycardia refractory to drug treatment, it may be necessary to install a temporary artificial pacemaker. In case of overdose, it is necessary to monitor the content of creatinine and electrolytes in the blood serum. Ramiprilat is poorly eliminated from the blood through hemodialysis.

special instructions

Information relating to ramipril and amlodipine is applicable to Egipres.

Amlodipine

In the treatment of hypertension, amlodipine can be combined with the administration of thiazide diuretics, alpha- and beta-blockers, ACE inhibitors, long-acting nitrates, sublingual nitroglycerin, NSAIDs, antibiotics and hypoglycemic agents for oral administration.

In the treatment of angina, amlodipine can be prescribed in combination with other antianginal drugs, including patients refractory to treatment with nitrates and / or beta-blockers in adequate doses.

Amlodipine does not have any adverse effect on the metabolism and plasma lipids and can be used in the treatment of patients with bronchial asthma, diabetes and gout.

Amlodipine can also be used in cases where the patient is prone to vasospasm / vasoconstriction.

Patients with low body mass, short stature and patients with severe liver dysfunction may require a lower dosage.

During treatment, body weight control and monitoring by a dentist is necessary (to prevent pain, bleeding and gum hyperplasia).

Ramipril

Before starting treatment with ramipril, it is necessary to eliminate hyponatremia and hypovolemia. Patients who have previously taken diuretics need to cancel them or at least reduce their dose 2-3 days before starting ramipril (in this case, you should regularly monitor the condition of patients with CHF due to the possibility of their decompensation with an increase in BCC).

After taking the first dose of Egipres, as well as increasing its dose and / or diuretic dose (especially loop), it is necessary to ensure regular medical observation of the patient for at least 8 hours in order to take appropriate measures in the event of an excessive decrease in blood pressure.

If ramipril is used for the first time or in a high dose in patients with increased RAAS activity, then they should regularly monitor their blood pressure, especially at the beginning of treatment, because these patients have an increased risk of excessive blood pressure reduction. In case of malignant hypertension and HF, especially in the acute stage of myocardial infarction, treatment with ramipril should be started only in the hospital setting.

In patients with CHF, Egipres may lead to the development of a pronounced decrease in blood pressure, which in some cases is accompanied by oliguria or azotemia and rarely by the development of acute renal failure.

Care should be taken when treating elderly patients, since they may be particularly sensitive to ACE inhibitors; In the initial phase of treatment, it is recommended to monitor indicators of renal function.

In patients for whom a decrease in blood pressure may pose a certain risk (for example, patients with atherosclerotic narrowing of the coronary or cerebral arteries), treatment should begin under strict medical supervision.

Caution should be exercised during physical exertion and / or hot weather due to the risk of sweating and dehydration with the development of arterial hypotension due to a decrease in BCC and a decrease in sodium content in the blood.

Alcohol is not recommended during treatment.
Transient hypotension is not a contraindication to continue treatment after stabilization of blood pressure. In the case of recurrence of severe hypotension, reduce the dose or discontinue Egipres. In patients treated with ACE inhibitors, there have been cases of angioedema of the face, extremities, lips, tongue, pharynx, or larynx. If swelling occurs in the face (lips, eyelids) or tongue, or a violation of swallowing or breathing, the patient should immediately stop taking Egipres. Angioedema, localized in the area of ​​the tongue, pharynx or larynx (possible symptoms: impaired swallowing or breathing), can be life-threatening and requires urgent measures to relieve it: s / c administration 0.3-0.5 mg or IV drip the introduction of 0.1 mg of epinephrine (under the control of blood pressure, heart rate and ECG), followed by the use of corticosteroids (IV, IV, or orally); It is also recommended in / in the introduction of antihistamines (antagonists of H1 and H2-histamine receptors), and in case of insufficiency of C1-esterase enzyme inactivators, the need to introduce inhibitors of the C1-esterase enzyme in addition to epinephrine may be considered. The patient should be hospitalized and should be monitored until the symptoms are relieved, but not less than 24 hours.

Patients treated with ACE inhibitors were observed cases of intestinal angioedema, which was manifested by abdominal pain with nausea and vomiting or without them; in some cases, angioedema of the face was observed simultaneously. When a patient with the above described symptoms develops during the treatment of the differential diagnosis, the possibility of developing intestinal angioedema in their patients should also be considered.

Treatment aimed at desensitization to the poison of insects (bees, wasps), and the simultaneous use of ACE inhibitors can initiate anaphylactic and anaphylactoid reactions (such as lowering blood pressure, shortness of breath, vomiting, allergic skin reactions), which can sometimes be life-threatening. During treatment with ACE inhibitors, hypersensitivity reactions to insect venom (for example, bees, wasps) develop faster and are more difficult. If it is necessary to conduct desensitization to the poison of insects, then the ACE inhibitor should be temporarily replaced by the corresponding drugs of another class.

When using ACE inhibitors, life-threatening, rapidly developing anaphylactoid reactions have been described, sometimes up to the development of shock during hemodialysis or plasma filtration using certain high-flow membranes (for example, polyacrylonitrile membranes) (see also instructions of membrane manufacturers). It is necessary to avoid the joint use of ramipril and such kind of membranes (for example, for urgent hemodialysis or hemofiltration). In this case, it is preferable to use other membranes or exclude the use of an ACE inhibitor. Similar reactions were observed in LDL apheresis using dextran sulfate. Therefore, this method should not be used in patients receiving an ACE inhibitor. In patients with impaired liver function, the reaction to treatment with ramipril can be either enhanced or weakened. In addition, in patients with severe liver cirrhosis with edema and / or ascites, significant activation of the RAAS is possible, therefore, special care should be taken in treating these patients.

Before surgery (including dental), it is necessary to warn the surgeon / anesthesiologist about the use of an ACE inhibitor.
The use of an ACE inhibitor in patients undergoing extensive surgery and / or general anesthesia can lead to a pronounced decrease in blood pressure if agents are used for general anesthesia with hypotensive action. This is due to the blocking of the formation of angiotensin II against the background of a compensatory increase in renin activity. In this case, increase the volume of circulating fluid. It is recommended to stop taking an ACE inhibitor 24 hours before surgery. Based on the results of epidemiological studies, it is assumed that the simultaneous intake of ACE inhibitors and insulin, as well as hypoglycemic agents for oral administration can lead to the development of hypoglycemia. The greatest risk of development is observed during the first weeks of combination therapy, as well as in patients with impaired renal function.

Patients with diabetes require regular glycemic control, especially during the first month of treatment with ACE inhibitors.

It is recommended to carefully monitor newborns who have been exposed to prenatal ACE inhibitors to detect arterial hypotension, oliguria and hyperkalemia.

When oliguria, it is necessary to maintain blood pressure and renal perfusion by injecting appropriate fluids and vasoconstrictor agents.

These newborns are at risk of developing oliguria and neurological disorders, possibly due to a decrease in renal and cerebral blood flow due to a decrease in blood pressure caused by ACE inhibitors.

During therapy with ACE inhibitors, a dry cough may occur. Coughing persists while taking this group of drugs and disappears after they are canceled. When a patient has a dry cough, you should be aware of the possible iatrogenic nature of this symptom.

Patients of the Negroid race are more likely to develop angioedema than on other races while taking ACE inhibitors. Ramipril, like other ACE inhibitors, may have a less pronounced antihypertensive effect in patients of the Negroid race compared to other races. Perhaps this difference is due to the fact that in patients of the Negroid race with AH, low renin activity is more often observed.

Monitoring of laboratory parameters before and during ramipril treatment (up to 1 time per month in the first 3-6 months of treatment) includes:

- control of renal function (determination of serum creatinine). When treating with ACE inhibitors in the first weeks of treatment and subsequently it is recommended to monitor kidney function. Especially careful monitoring is required for patients with HF, impaired renal function, after kidney transplantation, patients with renovascular diseases, including patients with hemodynamically significant unilateral renal artery stenosis in the presence of two kidneys (in these patients even a slight increase in serum creatinine may be an indicator of a decrease in kidney function ).

- control of electrolyte content. Regular monitoring of serum potassium is recommended. Particularly careful monitoring of serum potassium is required in patients with impaired renal function, significant impairment of water and electrolyte balance, CHF.

- control of hematological parameters (hemoglobin content, white blood cell count, red blood cell count, platelet count, leukocyte count). It is recommended to monitor the parameters of the complete blood count to detect possible leukopenia. More regular monitoring is recommended at the beginning of treatment and in patients with impaired renal function, as well as in patients with connective tissue diseases or in patients receiving other drugs at the same time that can change the pattern of peripheral blood.

Control of the number of leukocytes is necessary for early detection of leukopenia, which is especially important in patients with an increased risk of its development, as well as at the first signs of infection. If neutropenia is detected (the number of neutrophils is less than 2000 / μl), treatment with ramipril is required. If symptoms arise due to leukopenia (for example, fever, swollen lymph nodes, tonsillitis), urgent monitoring of the peripheral blood pattern is necessary. In case of signs of bleeding (the smallest petechiae, red-brown eruptions on the skin and mucous membranes), it is also necessary to control the number of platelets in the peripheral blood.

- determination of the activity of liver enzymes, the concentration of bilirubin in the blood. If jaundice or a significant increase in liver enzyme activity occurs, ramipril treatment should be stopped and the patient should be monitored by a doctor.
Influence on ability to steer vehicles and work with mechanisms. During the period of drug treatment, it is recommended to refrain from driving and engaging in other potentially hazardous activities that require increased concentration and psychomotor speed (dizziness is possible, especially at the beginning of treatment, and in patients taking diuretic drugs, decreased concentration) dose, as well as after a significant increase in the dose of Egipres is not recommended to drive a vehicle and work with technical equipment during several hours.

Release form

Capsules, 5 mg + 5 mg, 5 mg + 10 mg, 10 mg + 5 mg, 10 mg + 10 mg. 10 caps. in a blister of the combined film “cold” (polyamide / aluminum foil / PVC) / aluminum foil. 3 blisters (10 caps) in a carton box.
Storage conditions of the drug Egipres
At a temperature not higher than 25 ° C.
Keep out of the reach of children.
Expiration drug shelf life - 3 years.
Do not use after the expiration date printed on the package.

Terms of sell

You can buy Egipres without a prescription.