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

active substance: ramipril in terms of 100% substance - 1.25 mg; Excipients', lactose monohydrate - 82.7 mg; sodium hydrogen carbonate - 0.3 mg; cellulose microcrystalline - 10 mg; hypromellose - 0.5 mg; arginine - 0.15 mg; croscarmellose sodium - 2 mg; silicon dioxide colloidal - 1 mg; silicon dioxide, methylated (colloidal silicon dioxide, hydrophobic) - 1 mg; sodium stearyl fumarate - 1 mg; dye iron oxide yellow -0.1 mg.

One 2.5 mg tablet contains:

active substance', ramipril in terms of 100% substance - 2.5 mg; Excipients', lactose monohydrate - 165.4 mg; sodium hydrogen carbonate - 0.6 mg; cellulose microcrystalline - 20 mg; hypromellose - 1 mg; arginine 0.3 mg; croscarmellose sodium - 4 mg; silicon dioxide colloidal - 2 mg; silicon dioxide, methylated (colloidal silicon dioxide, hydrophobic) - 2 mg; sodium stearyl fumarate - 2 mg; ferric iron oxide yellow - 0.2 mg.

One 5 mg tablet contains:

active substance: ramipril in terms of 100% substance-5 mg;

Excipients: lactose monohydrate - 103.4 mg; sodium bicarbonate - 1.2 mg; cellulose microcrystalline - 13 mg; hypromellose - 0.65 mg; arginine 0.2 mg; croscarmellose sodium - 2.6 mg; silicon dioxide colloidal - 1.3 mg; silicon dioxide, methylated (colloidal silicon dioxide, hydrophobic) - 1.3 mg; sodium stearyl fumarate -1,3 mg; ferric oxide red oxide - 0.05 mg.

One 10 mg tablet contains:

active substance', ramipril in terms of 100% substance - 10 mg; Excipients: lactose monohydrate - 206.8 mg; sodium hydrogen carbonate - 2.4 mg; microcrystalline cellulose - 26 mg; hypromellose - 1.3 mg; arginine 0.4 mg;croscarmellose sodium - 5.2 mg; silicon dioxide colloid - 2,6 mg; silicon dioxide, methylated (silicon dioxide colloidal hydrophobic) - 2.6 mg; sodium stearyl fumarate - 2.6 mg; dye iron oxide red - 0.1 mg.

Description:

Round tablets of flat-cylindrical shape, with a bevel, tablets with a dosage of 10 mg are at risk. Tablets with dosages of 1.25 mg and 2.5 mg from light yellow to yellow are allowed to be incrusted. Tablets with a dosage of 5 mg and 10 mg of light pink with a brownish tinge to pink, are allowed inclusions.

Pharmacotherapeutic group:ACE inhibitor

ATX: & nbsp

C.09.A.A ACE Inhibitors

C.09.A.A.05 Ramipril

Pharmacodynamics:

The active metabolite of ramipril-ramiprilat, formed under the influence of "liver" enzymes, is a long-acting ACE inhibitor, which is a dipeptidylcarboxyldipeptidase I. ACE in the blood plasma and tissues catalyzes the conversion of angiotensin I into angiotensin II and the breakdown of bradykinin.

Therefore, when taking ramipril, the formation of angiotensin II decreases and the accumulation of bradykinin occurs, which leads to vasodilation and a decrease in blood pressure (BP).The increased activity of the kallikrein-kinin system in blood and tissues causes cardioprotective and endothelioprotective action of ramipril due to activation of the prostaglandin system and, correspondingly, an increase in the synthesis of prostaglandins stimulating the formation of nitric oxide (N0) in endotheliocytes.

Angiotensin II stimulates the production of aldosterone, therefore, taking ramipril leads to a decrease in the secretion of aldosterone and an increase in the serum concentrations of potassium ions.

When the concentration of angiotensin II decreases in the blood, its inhibitory

influence on renin secretion by the type of negative feedback, which leads to

increase of renin activity of blood plasma.

It is assumed that the development of some unwanted reactions (in particular, "dry" cough) is also associated with an increase in bradykinin concentration.

In patients with hypertension taking ramipril leads to a decrease in blood pressure in the "lying" and "standing", without compensatory increase in the heart rate (heart rate). Ramipril significantly reduces the overall peripheral vascular resistance (OPSS), virtually without causing changes in the renal blood flow and glomerular filtration rate.The hypotensive effect begins to appear 1-2 hours after ingestion of a single dose of the drug, reaching the highest value in 3-6 hours, and persists for 24 hours. With the course of treatment, the hypotensive effect can gradually increase, stabilizing usually to 3-4 weeks of regular intake of the drug and then remaining for a long time. The sudden discontinuation of the drug does not lead to a rapid and significant increase in blood pressure (the absence of the "withdrawal" syndrome)

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

In patients with chronic heart failure ramipril reduces OPSS (decrease in heart afterload), increases the capacity of the venous bed and reduces the filling pressure of the left ventricle, which, accordingly, leads to a decrease in preload on the heart. In these patients, when taking ramipril, there is an increase in cardiac output, ejection fraction and improvement of exercise tolerance.

With diabetic and nondiabetic nephropathy the administration of ramipril slows the rate of progression of renal insufficiency and the time of onset of the terminal stage of renal failure and, as a result, reduces the need for hemodialysis or kidney transplantation procedures. At the initial stages of diabetic or nondiabetic nephropathy ramipril reduces the severity of albuminuria. Have patients with a high risk of developing cardiovascular diseases due to the presence of vascular lesions (diagnosed coronary heart disease, obliterating diseases of the peripheral arteries in history, a stroke in the anamnesis) or diabetes mellitus with at least one additional risk factor (microalbuminuria, hypertension, increased total cholesterol concentration (OX), lowering of cholesterol concentration of lipoproteins high-density (HDL-C), smoking) the addition of ramipril to standard therapy significantly reduces the incidence of myocardial infarction, stroke and Mortality from cardiovascular causes. Besides, ramipril reduces the overall mortality rate, as well as the need for revascularization procedures, and slows the onset or progression of chronic heart failure.

In patients with heart failure, developed in the early days of acute myocardial infarction (2-9 days), when taking ramipril, from 3 to 10 days of acute myocardial infarction, the risk of death rate (by 27%), risk of sudden death (by 30%), the risk of progression of chronic heart failure to severe (III-IV functional class according to the classification of IUNA-resistant to therapy (by 27%), the probability of subsequent hospitalization due to the development of heart failure (by 26%).

In the general population of patients, and in patients with diabetes mellitus, both with arterial hypertension and normal BP, ramipril significantly reduces the risk of developing nephropathy and the occurrence of microalbuminuria.

Pharmacokinetics:

After oral administration ramipril quickly absorbed from the gastrointestinal tract (50-60%). The intake of food slows down its absorption, but does not affect the completeness of absorption. Ramipril is subjected to intense presystemic metabolism / activation (mainly in the liver by hydrolysis), which results in the formation of its only active metabolite, ramiprilate, whose activity with respect to ACE inhibition is about 6 times that of ramipril.In addition, as a result of the metabolism of ramipril, diketopiperazine, which does not possess pharmacological activity, is formed, which is then subjected to conjugation with glucuronic acid. Ramiprilat is metabolized to diketopiperazic acid and glucuronates. The bioavailability of ramipril after ingestion varies from 15% (for a dose of 2.5 mg) to 28% (for a dose of 5 mg). The bioavailability of the active metabolite - ramiprilata - after ingestion of 2.5 mg and 5 mg of ramipril is approximately 45% (compared to its bioavailability after intravenous administration at the same doses).

After taking ramipril inside the maximum plasma concentrations (Сmах)

ramipril and ramiprilata in blood plasma are achieved after 1 and 2-4 hours, respectively.

The decrease in plasma concentration of ramiprilata occurs in several stages: the phase

distribution and elimination with a half-life (T_1\2) ramiprilata

approximately 3 hours, then an intermediate phase with T 1 /2, ramiprilata

about 15 hours, and a final phase with a very low concentration of ramiprilate in

blood plasma and T1 / 2, ramiprilata, which is about 4-5 days. This final

phase is due to the slow release of ramiprilate from a strong bond with

ACE receptors. Despite a prolonged final phase with a single daily ramipril intake of 2.5 mg or more, the equilibrium plasma concentration of ramiprilate is reached after approximately 4 days of treatment. With the prescription of the drug "effective" T1 / 2 depending on the dose is 13-17 hours.

Binding to blood plasma proteins approximately makes up 73% for ramipril, and 56% for ramiprilate.

After intravenous (iv) administration, the volume of distribution of ramipril and ramiprilate is approximately 90 liters and 500 liters, respectively.

After ingestion of radically labeled ramipril (10 mg), 39% of the radioactivity is excreted by the intestine and about 60% by the kidneys. After intravenous administration of ramipril, a 50-60% dose is detected in the urine in the form of ramipril and its metabolites. After intravenous administration of ramiprilate, about 70% of the dose is found in the urine in the form of ramiprilate and its metabolites, i.e. with / in the administration of ramipril and ramiprilata, a significant portion of the dose is excreted through the intestines with bile, bypassing the kidneys (50% and 30%, respectively). After takingInside 5 mg of ramipril in patients with bile duct drainage, virtually identical amounts of ramipril and its metabolites are excreted by the kidneys and intestines within the first 24 hours after ingestion. Approximately 80-90% of metabolites in urine and bile were identified as ramiprilate and metabolites of ramiprilate. Ramipril glucuronide and ramipril diketopiperazine constitute approximately 10-20% of the total, and the urinary content of unmetabolized ramipril is approximately 2%.

In animal studies, it was shown that ramipril is excreted with milk of lactating mice and rats, however, with repeated use in a dose of 10 mg ramipril and its metabolites create low concentrations in milk.

In case of violations of kidney function with creatinine clearance (CC) less than 60 ml / min, excretion of ramiprilate and its metabolites by the kidneys slows down. This leads to an increase in the plasma concentration of ramiprilate, which decreases more slowly than in patients with normal renal function.

When taking ramipril in high doses (10 mg), a violation of liver function leads to a slowing of the pre-system metabolism of ramipril to active ramiprilate and a slower elimination of ramiprilate.

In healthy volunteers and in patients with hypertension after 2 weeks of ramipril in a daily dose of 5 mg, there is no clinically significant accumulation of ramipril and ramiprilate. In patients with chronic cardiac

insufficiency after 2 weeks of ramipril treatment in a daily dose of 5 mg 1.5-1.8-fold increase in plasma concentrations of ramiprilate and the area under the pharmacokinetics curve "concentration-time" AUC.

In healthy elderly volunteers (65-76 years old), the pharmacokinetics of ramipril and ramiprilate are not significantly different from that of young healthy volunteers.

Indications:

Arterial hypertension (in monotherapy or in combination with other antihypertensive drugs);
chronic heart failure (as part of combination therapy, in particular, in combination with diuretics);
diabetic or nondiabetic nephropathy preclinical and clinically pronounced stages, incl. with pronounced proteinuria in particular, when combined with arterial hypertension;
reduction in the risk of myocardial infarction, stroke, or cardiovascular mortality in patients with high cardiovascular risk:

in patients with confirmed coronary heart disease (CHD), myocardial infarction in the history and without it, including patients who underwent percutaneous transluminal coronary angioplasty, coronary artery bypass grafting;
in patients with a history of stroke;
in patients with occlusal lesions of peripheral arteries in the anamnesis;
in patients with diabetes mellitus with at least one additional risk factor (microalbuminuria, arterial hypertension, increased plasma concentrations of OX, lower plasma concentrations of HDL-C, smoking);

heart failure with clinical manifestations, developed during the first few days (2-9 days) after acute myocardial infarction (see the section "Pharmaco dynamics").

Contraindications:

Hypersensitivity to ramipril, other ACE inhibitors, or to any of the components of the drug (see section "Composition");
angioedema (hereditary or idiopathic, as well as after taking ACE inhibitors in anamnesis) - the risk of rapid angioedema development (see section "Side effect");
hemodynamically significant stenosis of the renal arteries (bilateral or unilateral in the case of a single kidney);
arterial hypotension (systolic blood pressure less than 90 mm Hg.st.) or a condition with unstable hemodynamics;
hemodynamically significant stenosis of the aortic or mitral valve or hypertrophic obstructive cardiomyopathy;
primary hyperaldosteronism;
severe renal failure (CC less than 20 ml / min / 1.73 m²) (an experience

clinical use is insufficient).

hemodialysis (experience of clinical use is insufficient);
pregnancy;
the period of breastfeeding;
Nephropathy, which is treated with glucocorticosteroids (GCS),

non-steroidal anti-inflammatory drugs (NSAIDs),

immunomodulators and / or other cytotoxic agents (experience clinical use is insufficient, see the section "Interaction with other drugs");

chronic heart failure in the stage of decompensation (experience clinical use is inadequate);

age under 18 years (experience of clinical use is absent);
hemodialysis or hemofiltration using some negatively charged membranes, such as high-flux polyacrylonitrile membranes (the risk of developing hypersensitivity reactions).sections "Interaction with other medicinal products", "Special instructions");
apheresis of low-density lipoprotein (LDL) using dextran sulfate (the risk of developing hypersensitivity reactions) (see section "Special instructions");
hyposensitizing therapy in reactions of hypersensitivity to poisons of Hymenoptera insects such as bees, wasps (see section "Special instructions");
simultaneous use with aliskiren and aliskirenoderzhaschimi drugs in patients with diabetes mellitus and / or renal dysfunction (glomerular filtration rate (GFR) less than 60 ml / min);
simultaneous use with angiotensin II receptor antagonists in patients with diabetic nephropathy;
intolerance to galactose, deficiency of lactase and glucose-galactose malabsorption syndrome.

Additional contraindications for the use of the drug in the acute stage of myocardial infarction:

severe heart failure (functional class IV according to classification NYHA);
unstable angina;
life-threatening ventricular arrhythmias;
"pulmonary" heart.

Carefully:

conditions in which excessive reduction in blood pressure is particularly dangerous (with atherosclerotic lesions of the coronary and cerebral arteries);
states, accompanied by an increase in the activity of the renin-angiotensin-aldosterone system (RAAS), in which, with the inhibition of ACE, there is a risk of a sharp decrease in blood pressure with impaired renal function:

severe arterial hypertension, especially malignant hypertension;
chronic heart failure, especially severe or about which other drugs with hypotensive action are taken;
hemodynamically significant unilateral stenosis of the renal artery (in the presence of both kidneys);
previous administration of diuretics;
simultaneous application of ramipril with aliskiren containing preparations, or antagonists of receptors for angiotensin II (with double blockade of RAAS), there is an increased risk of a marked decrease in blood pressure, the development of hyperkalemia and worsening of kidney function in comparison with monotherapy;
disturbance of water-electrolyte balance as a result of insufficient intake of liquid and table salt, diarrhea, vomiting, profuse sweating;

impaired liver function (insufficient experience of application: it is possible both to strengthen and weaken the effects of ramipril, in patients with cirrhosis of the liver with ascites and edema, a significant activation of RAAS is possible, see above

"Conditions accompanied by increased activity of the RAAS");

impaired renal function (QC more than 20 ml / min / 1.73 m2) because of the risk of hyperkalemia and leukopenia;
condition after kidney transplantation;
systemic connective tissue diseases, incl. systemic lupus erythematosus, scleroderma, concomitant therapy with drugs capable of causing changes in the pattern of peripheral blood (possibly oppression of bone marrow hematopoiesis, development of neutropenia or agranulocytosis, see section "Interaction with other drugs");
diabetes mellitus (risk of hyperkalemia);
elderly age (risk of increased hypotensive effect);
hyperkalemia.

Pregnancy and lactation:

Ramepress ® is contraindicated in pregnancy, as it can adversely affect the fetus: impairment of fetal kidney development, fetal and neonatal fetal decline, renal dysfunction, hyperkalemia, skull bones hypoplasia, oligohydramnios, limb contracture, skull bones deformation, lung hypoplasia.

Therefore, before starting the drug in women of reproductive age, pregnancy should be excluded.

If a woman is planning a pregnancy, treatment with ACE inhibitors should be discontinued.

In case of pregnancy during treatment with the drug Ramepress ®, it should be stopped as soon as possible and transferred to the patient for taking other drugs, in which application the risk for the child will be the least.

If treatment with Ramepress ® is necessary during breastfeeding, then breastfeeding should be discontinued.

Dosing and Administration:

The drug Ramepress ® taken inside, swallowing whole (without chewing) and squeezed enough (1/2 glass) of water, regardless of food intake (ie tablets can be taken before, during or after meals). The dose is selected depending on the therapeutic effect and the tolerance of the drug to the patient.

Treatment with Ramepress ® is usually long, and its duration in each case is determined by the doctor.

If not prescribed otherwise, then with normal kidney and liver function, the following dosing regimens are recommended.

With arterial hypertension

Usually the initial dose of Ramepress ® is 2.5 mg once a day in the morning. If, when taking the drug at this dose for 3 weeks or more, it is not possible to normalize blood pressure, then the dose can be increased to 5 mg of ramipril per day. With an inadequate dose of 5 mg in 2-3 weeks, it can be doubled to the maximum recommended daily dose of 10 mg per day.

As an alternative to increasing the dose to 10 mg per day with insufficient therapeutic efficiency of a daily dose of 5 mg, it is possible to add to the treatment of other antihypertensive agents, in particular diuretics or slow calcium channel blockers (BCCC).

With chronic heart failure

The recommended initial dose of Ramepress ® is 1.25 mg once a day. Depending on the patient's reaction to the therapy, the dose may increase. It is recommended to double the dose at intervals of 1-2 weeks. If a daily dose of 2.5 mg or more is required, it can be taken as a single dose per day or divided into 2 doses.

The maximum recommended daily dose is 10 mg.

With diabetic or nondiabetic nephropathy

The recommended initial dose of Ramepress ® is 1.25 mg once a day.The dose can be increased to 5 mg once a day. At these dose states more than 5 mg once a day in controlled clinical trials have not been adequately studied. To reduce the risk of developing myocardial infarction, stroke, or cardiovascular mortality in patients with high cardiovascular risk The recommended initial dose of Ramepress ® is 2.5 mg once a day.

Depending on the tolerability of the drug, the patient can gradually increase the dose. It is recommended to double the dose after 1 week of treatment, and during the next 3 weeks of treatment - increase it to the usual maintenance dose of 10 mg once a day. Doses in excess of 10 mg in controlled clinical trials have not been adequately studied.

The use of the drug Ramepress ® in patients with CK less than 0.6 ml / s has been studied insufficiently.

In heart failure, developed during the first few days (2-9 days) after acute myocardial infarction

The recommended initial dose of drug Ramepress® - 5 mg per day, divided into 2 single doses of 2.5 mg, one of which is taken in the morning, and the second - in the evening. If the patient can not tolerate the initial dose (there is an excessive reduction in blood pressure), then it is recommended for two days to give 1.25 mg 2 times a day.

Then, depending on the patient's reaction, the dose can be increased. It is recommended that the dose at its increase is doubled with an interval of 1-3 days. Later, the total daily dose, which was initially divided into two doses, can be given only once.

The maximum recommended dose is 10 mg.

Currently, the experience of treatment patients with severe heart failure (III-IV functional class by classification NYHA), which occurred immediately after an acute myocardial infarction, is inadequate. If such patients decide to undergo treatment with Ramepress ®, it is recommended that treatment start with the lowest possible dose, 1.25 mg once a day, and that extra care should be taken with each dose increase.

Use of Ramepress ® in selected patient groups Patients with impaired renal function

With SC from 50 to 20 ml / min / 1.73 m² the initial daily dose is usually 1.25 mg. The maximum permissible daily dose is 5 mg.

Patients with incompletely adjusted loss of fluid and electrolytes, patients with severe arterial hypertension, as well as patients,for which an excessive decrease in blood pressure poses a certain risk (for example, in severe atherosclerotic lesions of the coronary and cerebral arteries)

The initial dose is reduced to 1.25 mg per day.

Patients with prior diuretic therapy

It is necessary, if possible, to cancel diuretics for 2-3 days (depending on the duration of the action of diuretics) before starting treatment with Ramepress ®, or at least reduce the dose of diuretics taken.

Treatment of such patients should begin with the lowest dose, equal to 1.25 mg of ramipril, taken once a day, in the mornings. After taking the first dose and every time after increasing the dose of ramipril and (or) loop diuretics, patients should be under medical supervision for at least 8 hours in order to avoid an uncontrolled hypotensive reaction.

Patients of advanced age (over 65 years)

The initial dose is reduced to 1.25 mg per day.

Patients with hepatic impairment

The response of blood pressure to the drug Ramepress ® can both increase (by slowing the excretion of ramiprilate) and decrease (by slowing the conversion of low-active ramipril to active ramiprilate).

Therefore, at the beginning of treatment, careful medical supervision is required.The maximum allowable daily dose is 2.5 mg.

Side effects:

The undesirable effects listed below are given in accordance with the following gradations of their frequency: very often (> 10%); often (> 1%, <10%); infrequently (> 0.1%, <1%); rarely (> 0.01%, 0.1%); very rarely (<0.01%, including individual messages); frequency is unknown (according to available data, it is not possible to establish the frequency of occurrence).

Violations from the heart-, infrequently - myocardial ischemia, including the development of an attack of angina or myocardial infarction, tachycardia, arrhythmia (appearance or gain), palpitations, peripheral edema.

Vascular disorders: often - excessive decrease in blood pressure, violation of orthostatic regulation of vascular tone (orthostatic hypotension), syncopal conditions; infrequently - "tides" of blood to the skin of the face; rarely - the occurrence or intensification of circulatory disorders against the background of stenosing vascular lesions, vasculitis; frequency is unknown - Raynaud's syndrome.

Disturbances from the nervous system: often - headache, dizziness (feeling of "lightness" in the head); infrequently - vertigo, paresthesia,agevzia (loss of taste sensitivity), dysgeusia (a violation of taste sensitivity); rarely - tremor, imbalance; the frequency of unknown ischemia of the brain, including ischemic stroke and transient impairment of cerebral circulation, violation of psychomotor reactions, burning sensation, parosmia (impaired perception of odors). Disturbances on the part of the organ of sight: infrequent - visual disorders, including blurred vision; rarely - conjunctivitis.

Violations from the organ of hearing, rarely - hearing loss, ringing in the ears.

Disorders of the psyche-, infrequently - depression, anxiety, nervousness, motor anxiety, sleep disturbances, including drowsiness; rarely confusion; frequency unknown - attention violation.

Disturbances from the respiratory system: often - a "dry" cough (worse

at night and in the "lying" position), bronchitis, sinusitis, dyspnea; infrequently - bronchospasm, including weighting of the course of bronchial asthma, congestion of the nose.

Disorders from the gastrointestinal tract: often - inflammatory reactions in the stomach and intestines, digestive disorders, discomfort in the abdomen, dyspepsia, diarrhea, nausea, vomiting; infrequently - fatal pancreatitis, incl.and fatal cases (cases of pancreatitis with a lethal outcome with the intake of ACE inhibitors were very rare), increased activity of pancreatic enzymes in the blood plasma, intestinal angioedema, pain in the upper abdomen, incl. associated with gastritis, constipation, dryness of the oral mucosa; rarely glossitis; frequency unknown - aphthous stomatitis (inflammatory reaction of the mucous membrane of the oral cavity).

Disturbances from the liver and bile ducts', infrequently - increased activity of "hepatic" enzymes and concentration of conjugated bilirubin in blood plasma; rarely - cholestatic jaundice, hepatocellular lesions; frequency unknown - acute hepatic insufficiency, cholestatic or cytolytic hepatitis (lethal outcome was observed extremely rarely).

Disorders from the kidneys and urinary tract: infrequent - renal dysfunction, including acute renal failure, increased urine output, increased pre-existing proteinuria, increased urea and creatinine levels in the blood.

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

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

Disturbances from the skin and subcutaneous tissues', often - skin rash, in particular, maculopapular; infrequently - angioedema, incl. and fatal (laryngeal edema can cause airway obstruction leading to death), skin itching, hyperhidrosis (increased sweating); rarely exfoliative dermatitis, urticaria, onycholysis; very rarely photosensitization reactions; frequency unknown-toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, weight gain of psoriasis, psoriasis-like dermatitis,pemphigoid or lichenoid (lichen) exanthema or enanthema, alopecia.

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

Disorders from the endocrine system: frequency unknown - syndrome

inadequate secretion of antidiuretic hormone.

Disorders from the metabolism and nutrition: often - an increase in the concentration of potassium in the blood; infrequently - anorexia, decreased appetite; the frequency is unknown - the decrease in the concentration of sodium in the blood.

Immune system disorders: frequency unknown - anaphylactic or anaphylactoid reactions (with ACE inhibition, the amount of anaphylactic or anaphylactoid reactions to insect venoms increases), an increase in the titer of antinuclear antibodies.

Common violations: often - pain in the chest, a feeling of fatigue; infrequent - increase in body temperature; rarely - asthenia (weakness).

Overdose:

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

Treatment: gastric lavage, the appointment of adsorbents (if possible within the first 30 minutes). In the case of a pronounced decrease in blood pressure to therapy for replenishment of bcc and restoration of the water-electrolyte balance, addition of alpha1-adrenergic agonists (norepinephrine), dopamine and angiotensinamide. In the case of refractory to medical treatment of bradycardia, a temporary artificial pacemaker may be required. In case of an overdose, it is necessary to monitor serum concentrations of creatinine and electrolytes.

Interaction:

Contraindicated combinations

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 the apheresis of LDL-risk development of severe anaphylactic reactions.

Simultaneous use with aliskiren and aliskirenoderzhaschimi drugs in patients with diabetes mellitus and / or renal dysfunction (GFR less than 60 ml / min).

With vildagliptin - in patients taking both ACE inhibitors and vildagliptin, there was an increase in the incidence of angioedema.

With inhibitors mTOR (for example, tamsirolimus) - in patients taking both ACE inhibitors and inhibitors mTOR, there was an increase in the incidence of angioedema.

Not recommended combinations

With potassium salts, potassium-sparing diuretics (for example, amiloride, triamterene, spironolactone, eplerenone (spironolactone derivative)) - a more pronounced increase in serum potassium concentration is possible (with simultaneous use, regular monitoring of potassium concentration in the blood serum is required).

Combinations that should be used with caution

With hypotensive drugs (eg, diuretics) and other drugs that can reduce blood pressure (nitrates, tricyclic antidepressants, general and local anesthetics, baclofen, alfuzosin, doxazosin, prazosin, tamsulosin, terazosin) - potentiation of the hypotensive effect; for the combination with diuretics, see also the sections "Dosing and Administration", "Side effect", "Special instructions", when combined with diuretics, the sodium content in serum should be monitored.

With sleeping pills, narcotics and anesthetics - perhaps a more pronounced decrease in blood pressure.

With vasopressornym sympathomimetics (epinephrine, isoproterenol, dobutamine, dopamine) - a decrease in the hypotensive effect of ramipril, requires a particularly careful control of blood pressure.

With allopurinol, procainamide, cytostatics, immunosuppressants, corticosteroids (glucocorticosteroids and mineralocorticosteroids) and other agents that may affect hematologic indices - joint use increases the risk of hematological reactions (see section "Special instructions"),

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

lithium in the blood serum.

With hypoglycemic agents for oral administration (derivatives of sulfonylurea, biguanides), insulin - in connection with a decrease in insulin resistance under the influence of ACE inhibitors, it is possible to increase the hypoglycemic effect of these drugs, up to the development of hypoglycemia.It is recommended that blood glucose concentration be carefully monitored at the beginning of the joint use of these drugs with ACE inhibitors.

Combinations that should be taken into account

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

With heparin - it is possible to increase the potassium content in the blood serum.

With sodium chloride, weakening of the hypotensive effect of ramipril and less effective treatment of symptoms of chronic heart failure.

With ethanol - increased vasodilation. Ramipril can enhance the effects of ethanol on the body.

With estrogens, weakening of the hypotensive effect of ramipril (fluid retention). Desensitizing therapy with hypersensitivity to insect venom-ACE inhibitors, including ramipril, increase the likelihood of developing severe anaphylactic or anaphylactoid reactions to insect venoms. It is assumed that this effect can occur when other allergens are used.

Special instructions:

Before starting treatment with the drug Ramepress ® it is necessary to eliminate hyponatremia and hypovolemia. In patients previously treated with diuretics, it is necessary to cancel them or at least reduce their dose for 2-3 days before you start taking ramipril (in this case, should carefully monitor the condition of patients with chronic heart failure, due to the possibility of their decompensation with increasing bcc).

After taking the first dose of the drug, as well as increasing its dose and / or dose

diuretics (especially "loop"), it is necessary to provide a thorough medical

Monitoring of the patient for at least 8 hours for timely adoption

appropriate measures in case of excessive blood pressure lowering. If the drug Ramepress ®

is used for the first time or in a high dose in patients with increased activity of RAAS,

then they should carefully monitor blood pressure, especially at the beginning of treatment, tk. these patients there is an increased risk of excessive blood pressure lowering (see "With caution").

The simultaneous use of ramipril with aliskirensoderzhaschimi drugs or antagonists of angiotensin II (when dual blockade of the RAAS) have an increased risk of significant decrease in blood pressure,the development of hyperkalemia and worsening of kidney function in comparison with monotherapy.

With malignant arterial hypertension and heart failure, especially in the acute stage of myocardial infarction, treatment with Ramepress ® should be started only in a hospital.

In patients with chronic heart failure, taking the drug may lead to a marked decrease in blood pressure, which in some cases is accompanied by oliguria or azotemia and rarely - the development of acute renal failure.

Care should be taken when treating elderly patients. they may be particularly sensitive to ACE inhibitors; in the initial phase of treatment it is recommended to monitor the indicators of kidney function (see also the section "Method of administration and dose").

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

Care should be taken with physical activity and / or hot weather because of the risk of increased sweating and dehydration with the development of arterial hypotension due to a decrease in BCC and a decrease in the sodium content in the blood.

During treatment with Ramepress ® it is not recommended to drink alcohol. Transient arterial hypotension is not a contraindication for continuing treatment after stabilizing blood pressure. In the case of repeated occurrence of severe arterial hypotension, the dose should be reduced or the drug should be withdrawn.

Patients treated with ACE inhibitors experienced cases of angioedema of the face, extremities, lips, tongue, pharynx or larynx. If there is swelling in the face (lips, eyelids) or tongue, or a violation of swallowing or breathing, the patient should immediately stop taking Ramepress ®. Angioedema is localized in the tongue, pharynx or larynx (possible symptoms: impaired swallowing or breathing) may be life threatening and requires urgent measures for its cupping: 0.3-0.5 mg subcutaneous injection or intravenous drip 0.1 mg epinephrine (adrenaline) (under the control of blood pressure, heart rate and ECG) followed by the use of GCS (iv, in / m, or inside);

It is also recommended iv administration of antihistamines (antagonists Hi- and Hg-histamine receptors), and in the case of inactivation of enzyme inactivators Ci- esterase, it may be necessary to consider the addition of enzyme C inhibitors in addition to epinephrinei-esterase. The patient should be hospitalized and monitored until the symptoms come to a complete relief, but not less than 24 hours.

In patients receiving ACE inhibitors, there were cases of intestinal angioedema, which manifested itself with abdominal pain with or without nausea and vomiting; in some cases, angioedema has also been observed. This condition was diagnosed during CT or ultrasound examination of the abdominal cavity or during a surgical procedure. When a patient appears on the background of treatment with ACE inhibitors of the above-described symptoms, it is necessary to consider the possibility of developing an intestinal angioedema in the course of a differential diagnosis.

Treatment aimed at desensitization to insect venom (bees, wasps), and simultaneous administration of ACE inhibitors can initiate anaphylactic and anaphylactoid reactions (eg, lowering blood pressure, dyspnea, vomiting, allergic skin reactions), which can sometimes be life threatening.Against the background of treatment with ACE inhibitors, hypersensitivity reactions to insect venom (eg, bees, wasps) develop more rapidly and take more severe course. If desensitization to insect venom is required, the ACE inhibitor should be temporarily replaced by a corresponding drug of another class.

With the use of 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 the drug Ramepress ® and such membranes (for example, for urgent hemodialysis or hemofiltration). In this case, it is preferable to use other membranes or to exclude the use of ACE inhibitors. Similar reactions were observed in the apheresis of LDL with the use of dextrin sulfate. Therefore, this method should not be used in patients receiving ACE inhibitors.

In patients with impaired hepatic function, the response to Ramepress ® can be either exacerbated or weakened.In addition, in patients with severe cirrhosis of the liver with edema and / or ascites, significant activation of RAAS is possible, therefore, special care must be taken in the treatment of these patients (see also "Dosage and Administration").

Before surgery (including dental surgery), it is necessary to alert the surgeon / anesthesiologist about the use of ACE inhibitors.

It is recommended to closely monitor newborns who have been exposed to intrauterine exposure to ACE inhibitors for the detection of arterial hypotension, oliguria and hyperkalemia. In oliguria it is necessary to maintain BP and renal perfusion by introducing appropriate fluids and vasoconstrictors. In such newborns, there is a risk of developing oliguria and neurological disorders, possibly due to a reduction in renal and cerebral blood flow due to a reduction in blood pressure caused by ACE inhibitors.

Control of laboratory parameters before and during treatment with Ramepress ® (up to 1 time per month in the first 3-6 months of treatment)

Control of kidney function (determination of serum creatinine concentrations)

In the treatment of ACE inhibitors in the first weeks of treatment and in the following it is recommended to monitor the function of the kidneys. Especially careful monitoring is required for patients with acute and chronic congestive heart failure, renal dysfunction, kidney transplant, patients with renovascular disease, including patients with hemodynamically significant unilateral renal artery stenosis with two kidneys (in these patients, even a slight increase in serum creatinine concentration may be an index of decreased renal function).

Controlling the concentration of electrolytes

Regular monitoring of potassium content in serum is recommended. Particularly careful monitoring of potassium in the blood serum is required for patients with impaired renal function, significant disturbances in water-electrolyte balance, chronic heart failure.

Control of hematological parameters (the cat (hemoglobin concentration, number of leukocytes, erythrocytes, platelets, leukocyte formula)

It is recommended to monitor the parameters of a general blood test to detect possible leukopenia.More frequent monitoring is recommended at the beginning of treatment and in patients with impaired renal function, and in patients with connective tissue disease, or in patients receiving concomitant other medicines capable of altering the peripheral blood picture (see. The section "Interaction with other drugs") . Control of leukocytes is necessary for the early detection of leukopenia, which is especially important in patients with an increased risk of developing it, as well as at the first signs of infection. If neutropenia is detected (the number of neutrophils is less than 2000 / μL), treatment with ACE inhibitors should be discontinued.

When symptoms appear due to leukopenia (eg, fever, enlargement of lymph nodes, tonsillitis), urgent monitoring of the picture of peripheral blood is needed. In case of signs of bleeding (the smallest petechiae, red-brown rashes on the skin and mucous membranes), it is also necessary to control platelets in the peripheral blood.

Determination of the activity of "liver" enzymes, the concentration of bilirubin in the blood When jaundice or significant increase in the activity of "liver" enzymes treatment with the drugRAMEPRESS® should be discontinued and medical supervision of the patient ensured.

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

During the treatment with Ramepress ® it is necessary to refrain from engaging in potentially dangerous activities, including motor vehicle management, which require an increased concentration of attention and speed of psychomotor reactions. on the background of its reception, there may be dizziness, decreased speed of psychomotor reactions, attention, especially after taking the first dose.

Form release / dosage:

Tablets of 1.25 mg, 2.5 mg, 5 mg and 10 mg.

30 tablets per bottle of polyethylene.

10 tablets per contour cell pack.

Each vial or 3 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Packaging:

30 tablets per bottle of polyethylene.

10 tablets per contour cell pack.

Each vial or 3 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002791

Date of registration:29.12.2014

The owner of the registration certificate:AKRIKHIN HFK, JSC AKRIKHIN HFK, JSC Russia

Manufacturer: & nbsp

AKRIKHIN HFK, JSC Russia

Information update date: & nbsp29.12.2014

Illustrated instructions

Instructions

Rampepress® (Ramepress ®)