RAMIPRIL-NANOLEC - instructions for use, dose, side effects, contraindications

	Amount, mg
	(2,5)	(5,0)	(10,0)
Active substance:
Ramipril	2,5	5,0	10,0
*Excipients:*
microcrystalline cellulose	61,60	60,0	56,50
lactose monohydrate	42,0	40,50	37,50
pregelatinized starch	30,0	28,10	24,75
hypromellose (hydroxypropylmethylcellulose)	7,5	7,5	7,5
sodium hydrogen carbonate	2,5	5,0	10,0
sodium stearyl fumarate	2,25	2,25	2,25
croscarmellose sodium (admixture)	1,5	1,5	1,5
colorant iron oxide yellow (E172)	0,15	0,0	0,0
iron dye red oxide (E172)	0,0	0,15	0,0

Description:

Round, flat-cylindrical tablets of light yellow or yellow color, with impregnations of a darker or light shade; with bevel (for a dosage of 2.5 mg).

Round, flat-cylindrical tablets of light pink or pink color, with impregnations of a darker or light shade; with bevel (for a dosage of 5 mg).

Round, flat-cylindrical tablets white or white with a yellowish hue; with bevel (for a dosage of 10 mg).

Pharmacotherapeutic group:ACE inhibitor

ATX: & nbsp

C.09.A.A ACE Inhibitors

C.09.A.A.05 Ramipril

Pharmacodynamics:

Formed under the influence of "liver" enzymes active metabolite of ramipril - ramiprilat - is a long-acting ACE inhibitor (ACE synonyms: kininaza II dipeptidylcarboxydipeptidase I). ACE in the blood plasma and tissues catalyzes the conversion of angiotensin I into angiotensin II, which has a vasoconstrictive effect, and the disintegration of bradykinin, which has a vasodilating action.

Therefore, when taking ramipril inward decreases the formation of angiotensin II and accumulation of bradykinin occurs, which leads to vasodilation and a decrease in blood pressure (BP). Ramipril-induced increase in the activity of the kallikrein-kinin system in blood and tissues with activation of the prostaglandin system and an increase in the synthesis of prostaglandins stimulating the formation of nitric oxideNO) in endothelial cells, cause its cardioprotective effect. With a decrease in angiotensin concentration II in the blood, its inhibitory effect on renin secretion by negative feedback is eliminated, which leads to an increase in renin activity in the 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 resistance of blood vessels (OPSS), virtually without causing changes in renal blood flow and glomerular filtration rate.Antihypertensive 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 a course of ramipril, the antihypertensive effect can gradually increase, stabilizing usually to 3-4 weeks of regular intake of the drug and then persisting for a long time. 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 (reduces afterload on the heart), 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.

In patients with a high risk of developing cardiovascular diseases due to the presence of vascular lesions (diagnosed ischemic heart disease, obliterating peripheral arterial diseases in history, a history of stroke) or diabetes mellitus with at least one additional risk factor (microalbuminuria, hypertension, increased total cholesterol concentrations, lower cholesterol concentrations 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), the use of ramipril, from 3 to 10 days of acute myocardial infarction, reduced mortality (by 27%), the risk of sudden death (by 30%), the risk of progression of chronic heart failure to severe (NYHA class III-IV functional class) / resistant to (by 23%), the likelihood of subsequent hospitalization due to the development of heart failure (by 26%).

In the general population of patients, as well as in patients with diabetes mellitus, both with arterial hypertension, and with 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 is not pharmacologically active, is formed, which is then conjugated with glucuronic acid, ramiprilate is also glucuronized and metabolized to diketopiperazic acid.

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 of ramipril and ramiprilata are reached after 1 and 2-4 hours, respectively.

The decrease in plasma concentration of ramiprilata occurs in several stages: the phase of distribution and excretion with a half-life (T_1/2) ramiprilata, which is about 3 hours, then the intermediate phase with T_1/2ramiprilata, about 15 hours, and a final phase with a very low concentration of ramipril in plasma and T_1/2ramiprilata, which is about 4-5 days.This final phase is due to the slow release of ramiprilata 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" T_1/2 depending on the dose is 13-17 hours.

The association with blood plasma proteins is about 73% for ramipril, and 56% for ramiprilate.

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

After ingestion of radically labeled ramipril (10 mg), 39% of the radioactivity is excreted through 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 ramiprilat, about 70% of the dose is found in the urine in the form of ramiprilate and its metabolites, in other words, with intravenous administration of ramipril and ramiprilate, a significant portion of the dose is excreted through the intestines with bile, bypassing the kidneys (50% and 30%, respectively).After ingesting 5 mg of ramipril in patients with bile duct drainage, virtually equal amounts of ramipril and its metabolites are excreted by the kidneys and through the intestine 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 urine content of unmetabolized ramipril is approximately 2%.

In animal studies, it was shown that ramipril excreted in breast milk.

In cases of renal dysfunction with creatinine clearance (CK) of 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 aftertwo weeks of ramipril treatment in a daily dose of 5 mg there is no clinically significant accumulation of ramipril and ramiprilate.

In patients with chronic heart failure after a two-week treatment with ramipril in a daily dose of 5 mg, there is a 1.5-1.8 fold increase in plasma concentrations of ramiprilate and the area under the pharmacokinetic 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, for example, diuretics and blockers of "slow" calcium channels);

- chronic heart failure (as part of combination therapy, in particular, in combination with diuretics);

- diabetic or nondiabetic nephropathy preclinical and clinically pronounced stages, including those with pronounced proteinuria in particular when combined with 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, myocardial infarction in or without anamnesis, including patients undergoing 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 (from the 2nd to the 9th day) after an acute myocardial infarction (see the section "Pharmacodynamics").

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 a history - the risk of rapid development of angioedema (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 (GOKMP);

- primary hyperaldosteronism;

- marked renal failure (CC less than 20 ml / min at body surface 1.73 m²) (experience of clinical use is insufficient);

- hemodialysis (experience of clinical use is insufficient);

- pregnancy;

- lactation period;

- nephropathy, treatment of which is carried out by glucocorticosteroids, nonsteroidal anti-inflammatory drugs, immunomodulators and / or other cytotoxic agents (clinical experience is not enough, see the section "Interaction with other drugs");

- Chronic heart failure in the stage of decompensation (the experience of clinical use is insufficient);

- age under 18 years (experience of clinical use is insufficient);

- hemodialysis or hemofiltration using some negatively charged membranes, such as high-flux polyacrylonitrile membranes (the risk of developing hypersensitivity reactions) (see.sections "Interactions with other drugs", "Special instructions");

- apheresis of low-density lipoproteins using dextran sulfate (the risk of developing hypersensitivity reactions) (see section "Special instructions");

- hyposensitizing therapy in reactions of hypersensitivity to poisons of insects, such as bees, wasps (see section "Special instructions");

- cardiogenic shock;

- severe hepatic insufficiency (no experience of clinical use);

- simultaneous use with aliskiren-containing drugs in patients with diabetes mellitus and renal insufficiency (CC less than 60 ml / min).

Additional contraindications for the use of the drug Ramipril in 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);

- conditions accompanied by increased activity of the renin-angiotensin-aldosterone system (RAAS),at which at an ACE inhibition there is a risk of sharp depression of a BP with deterioration of function of kidneys:

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;
disturbance of water-electrolyte balance as a result of insufficient intake of liquid and table salt, diarrhea, vomiting, profuse sweating;

- violations of the liver (lack of experience: it is possible both to enhance 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 RAAS");

- renal dysfunction (CC more than 20 ml / min at body surface 1.73 m²) because of the risk of developing hyperkalemia and leukopenia;

- condition after kidney transplantation;

- Systemic connective tissue diseases, including systemic lupus erythematosus,scleroderma, concomitant therapy with drugs that can cause changes in the picture of peripheral blood (possibly oppression of bone marrow hematopoiesis, development of neutropenia or agranulocytosis, see section "Interaction with other drugs");

- diabetes mellitus (the risk of hyperkalemia);

- Old age (risk of increased hypotensive effect);

- Hyperkalemia;

- simultaneous use of lithium drugs, immunosuppressants and saluretics.

Pregnancy and lactation:

Ramipril 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 childbearing 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 ramipril, it is necessary to stop as soon as possible its reception and transfer the patient to the reception of other drugs, in the application of which the risk to the child will be the least.

If the drug treatment ramipril it is necessary during lactation, then breastfeeding should be discontinued.

Dosing and Administration:

The tablets should be taken regardless of the meal (i.e., a tablet can be taken both before and during or after a meal) and drink plenty of (1/2 cup) of water. You can not chew or take pills before taking. The dose is selected depending on the therapeutic effect and the tolerance of the drug to the patient.

Treatment with the drug RAMIPRIL-NANOLEK® is usually lengthy, 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 essential hypertension

Usually the initial dose 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.If the dose of 5 mg is not effective 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 hypotensive efficacy of a daily dose of 5 mg, it is possible to add to the treatment of other antihypertensive agents, in particular, diuretics or blockers of "slow" calcium channels.

With chronic heart failure

The recommended initial dose: 1.25 mg * 1 time per day. Depending on the reaction to the patient's 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 given as a single dose per day or divided into 2 divided doses.

The maximum recommended daily dose is 10 mg.

With diabetic or nondiabetic nephropathy

The recommended initial dose: 1.25 mg * 1 time per 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: 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 in patients with KK less than 0.6 ml / sec has been studied insufficiently.

In heart failure with clinical manifestations that developed during the first few days (from the 2nd to the 9th day) after an acute myocardial infarction

The recommended initial dose is 5 mg per day, divided into two single doses of 2.5 mg, which are taken one morning, and the second - in the evening. If the patient does not tolerate this initial dose (there is an excessive decrease in blood pressure), then it is recommended to give 1.25 mg twice a day for two days.

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 treating 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 the drug RAMIPRIL-NANOLEC®, it is recommended that the treatment start with the lowest possible dose, 1.25 mg * 1 time per day, and special care should be taken with each dose increase.

Application of the drug RAMIPRIL-NANOLEC® in selected groups of patients

Patients with impaired renal function

With SC from 50 to 20 ml / min at 1.73 m² body surface area, 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 hypertension, as well as patients for whom excessive BP reduction 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 the drug RAMIPRIL-NANOLEC®, or at least reduce the dose of diuretics taken. Treatment of these patients should begin with the lowest dose, equal to 1.25 mg of ramipril, taken once a day, in the morning. 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 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 BP response to the administration of the RAMPIPRIL-NANOLEC® preparation can both be enhanced (by slowing the elimination of ramiprilate) and is weakened (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.

* In these cases, you can use other preparations of ramipril in the dosage form of a 2.5 mg tablet, with a risk.

Side effects:

According to the World Health Organization (WHO), the undesirable effects are classified according to their frequency of development as follows: very often (≥1/10), often (≥1 / 100 and <1110), not often (≥1 / 1,000 and < 1/100), rarely (≥1 / 10,000 and <1/1 000), very rarely (≥1 / 10000, including individual cases), the frequency is unknown - it is not possible to establish the frequency of occurrence according to available data.

Heart Disease:

Infrequently: myocardial ischemia, including the development of an attack of angina or myocardial infarction, tachycardia, arrhythmias (appearance or gain), palpitations, peripheral edema.

Vascular disorders:

Often: excessive reduction in blood pressure, violation of orthostatic regulation of vascular tone (orthostatic hypotension), syncopal conditions, "hot flashes" of the blood to the skin of the face, the appearance or increase of circulatory disorders against the background of stenosing vascular lesions, vasculitis;

Infrequently: "tides" of blood to the skin of the face;

Rarely: occurrence or strengthening of circulatory disorders against the background of stenosing vascular lesions, vasculitis;

Frequency unknown: Raynaud's syndrome.

Disturbances from the nervous system:

Often: headache, dizziness (a feeling of "lightness" in the head);

Infrequently: vertigo, paresthesia, agevzia (loss of taste sensitivity), dysgeusia (a violation of taste sensitivity);

Rarely: tremor, imbalance;

Frequency unknown: cerebral ischemia, including ischemic stroke and transient impairment of cerebral circulation, impaired psychomotor reactions (decreased response), burning sensation, parosmia (impaired perception of odors).

Disturbances on the part of the organ of sight:

Infrequently: visual disorders, including vagueness of the image;

Rarely: conjunctivitis.

Hearing disorders:

Rarely: hearing impairment, tinnitus (ringing in the ears).

Disorders of the psyche:

Infrequently: depressed mood, anxiety, nervousness, motor anxiety, sleep disturbances, including drowsiness;

Rarely: confusion of consciousness;

Frequency unknown: attention violation.

Disturbances from the respiratory system of the chest and mediastinal organs:

Often: "dry" cough (worse at night and lying down), bronchitis, sinusitis, dyspnea;

Infrequently: bronchospasm, including weighting of the course of bronchial asthma, nasal congestion.

Disorders from the gastrointestinal tract:

Often: inflammatory reactions in the stomach and intestines, digestive disorders, abdominal discomfort, dyspepsia, diarrhea, nausea, vomiting;

Infrequently: fatal pancreatitis (cases of pancreatitis fatal taking ACE inhibitors were observed rarely), increased activity of enzymes in the blood plasma of the pancreas, angioedema of the small intestine, pain in the upper abdomen, including those associated with gastritis, constipation, dry oral mucosa mouth;

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).

Violation of the kidneys and urinary tract:

Infrequently: a violation of kidney function, including the development of acute renal failure,increased urine output, increased pre-existing proteinuria, increased urea and creatinine concentrations 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, lymphadenopathy;

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, including fatal outcome (laryngeal edema can cause airway obstruction leading to death), skin itching, hyperhidrosis (excessive sweating);

Rarely: exfoliative dermatitis, urticaria, onycholysis;

Rarely: photosensitivity reaction;

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 and connective tissue:

Often: muscle cramps, myalgia;

Infrequently: arthralgia.

Disorders from the endocrine system:

Frequency unknown: syndrome of inadequate secretion of antidiuretic hormone (SNA ADH).

Disorders from the metabolism and nutrition:

Often: increasing the concentration of potassium in the blood;

Infrequently: anorexia, decreased appetite;

Frequency unknown: decrease in the concentration of sodium in the blood.

Immune system disorders:

Frequency unknown: anaphylactic or anaphylactoid reactions (with the inhibition of ACE, the amount of anaphylactic or anaphylactoid reactions to insect venoms increases), an increase in the concentration of antinuclear antibodies.

General disorders and disorders at the site of administration:

Often: pain in the chest, a feeling of fatigue;

Infrequently: increased 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: in mild cases, gastric lavage, intake of adsorbents (if possible within the first 30 minutes). It is necessary to monitor the function of vital organs. In the case of a marked decrease in blood pressure to therapy for replenishing the volume of circulating blood and restoring the electrolyte balance, the introduction of alphaa₁-adrenergic agonists (norepinephrine, dopamine) and angiotensin II (angiotensinamide). In the case of refractory to medical treatment of bradycardia, it may be necessary to install a temporary artificial pacemaker. In case of an overdose, it is necessary to monitor serum concentrations of creatinine and electrolytes.

Hemodialysis is indicated in cases of development of renal failure.

Interaction:

Contraindicated combinations

- Use of some high-flow membranes with a negatively charged surface (for example, polyacrylonitrile membranes) during hemodialysis or hemofiltration; use of dextransulfate in the apheresis of low density lipoproteins

Risk of development of severe anaphylactic reactions. If the patient needs these procedures, then other types of membranes should be used (in the case of plasmapheresis and hemofiltration) or the patient should be taken to receive other types of antihypertensive drugs.

- Simultaneous use of the drug Ramilil-Nanolek® and preparations containing aliskiren

The simultaneous use of the drug RAMIPRIL-NANOLEC® and preparations containing aliskiren, in patients with diabetes mellitus or renal failure with creatinine clearance <60 ml / min is contraindicated and not recommended in other patients (see the sections "Contraindications", "With caution", "Special instructions").

Unrecommended combinations

- With potassium salts, potassium-sparing diuretics (for example, amiloride, triamterene, spironolactone), other drugs capable of increasing the serum potassium content (including angiotensin II receptor antagonists, trimethoprim, tacrolimus, ciclosporin)

Perhaps more pronounced increase in potassium in the blood serum (with the simultaneous use requires careful monitoring of potassium in the blood serum).

Combinations that should be used with caution

- With antihypertensive drugs (eg, diuretics) and other drugs that can reduce blood pressure (nitrates, tricyclic antidepressants, agents for local and general anesthesia, baclofen, alfuzosin, doxazosin, prazosin, tamsulosin, terazosin)

Potentiation of antihypertensive effect: with regard to 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, narcotic and anesthetic drugs

Perhaps a more pronounced decrease in blood pressure.

- With vasopressor sympathomimetics (epinephrine, adrenolin, isoproterenol, dobutamine, dopamine)

Reduction of the antihypertensive effect of the drug RAMIPRIL-NANOLEC®, particularly careful control of blood pressure is recommended.

- With allopurinol, procainamide, cytostatics, immunosuppressants, corticosteroids and other drugs that can affect hematological parameters

Joint application increases the risk of hematological reactions (see section "Special instructions").

- FROM lithium salts

An increase in serum lithium concentration and an increase in the cardio- and neurotoxic effects of lithium. Therefore, the concentration of lithium in serum should be monitored.

- FROM hypoglycemic agents (for example, insulin, hypoglycemic agents for oral administration (derivatives and sulfonylureas))

In connection with the decrease in insulin resistance under the influence of ACE inhibitors, it is possible to increase the hypoglycemic effect of these drugs right 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.

- With vildagliptin

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

Combinations that should be taken into account

- With non-steroidal anti-inflammatory drugs (indomethacin, acetylsalicylic acid)

Possible weakening of the drug Ramipril-Nanolek®,increased risk of impaired renal function and increased serum potassium levels.

- With heparin

It is possible to increase the potassium content in the blood serum.

- With sodium chloride

Weakening of the antihypertensive effect of the drug RAMIPRIL-NANOLEC® and less effective treatment of symptoms of chronic heart failure.

- With ethanol

Increased symptoms of vasodilation. The drug RAMIPRIL-NANOLEC® can enhance the effect of ethanol on the body.

- With estrogens

Weakening of the antihypertensive effect of the drug RAMIPRIL-NANOLEC® (fluid retention).

- Desensitizing therapy with hypersensitivity to insect venoms

ACE inhibitors, including the preparation RAMIPRIL-NANOLEC®, increase the likelihood of 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 a drug of ramipril, it is necessary to eliminate hyponatremia and hypovolemia. In patients who have previously taken diuretics, it is necessary to cancel them, or at least reduce their dose 2-3 days before the start of taking the drug ramipril (in this case, carefully monitor the condition of patients with chronic heart failure, due to the possibility of developing their decompensation with increasing volume of circulating blood).

After taking the first dose of the drug, as well as increasing its dose and / or dose of diuretics (especially "loop"), it is necessary to ensure careful medical supervision of the patient for at least 8 hours to promptly take appropriate measures in case of excessive blood pressure lowering.

If the drug ramipril is used for the first time or in a high dose in patients with increased activity of RAAS, they should carefully monitor blood pressure, especially at the beginning of treatment, as these patients have an increased risk of excessive blood pressure lowering (see "With caution").

With malignant arterial hypertension and heart failure, especially in the acute stage of myocardial infarction, drug treatment ramipril the 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.

Caution should be exercised in the treatment of elderly patients, since they may be particularly sensitive to ACE inhibitors, it is recommended that the parameters of kidney function are monitored during the initial phase of treatment (see also 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 the volume of circulating blood and a decrease in the concentration of sodium in the blood.

During treatment with the drug ramipril 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 the drug. Angioedema, localized in the area of the tongue, pharynx, or larynx (possible symptoms: violation of swallowing or breathing), can be life threatening and requires urgent measures for its reduction: subcutaneous injection of 0.3-0.5 mg or intravenous drip introduction 0, 1 mg epinephrine (under the control of blood pressure, heart rate and ECG) followed by the use of glucocorticosteroids (iv, in / m, or inside); It is also recommended intravenous administration of antihistamines (antagonists H₁- and H₂-gistaminovyh receptors), and in case of insufficiency of inactivators of enzyme C₁-esterase can consider the need to introduce in addition to epinephrine inhibitors of the enzyme C₁-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.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 venoms (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 are more severe. If desensitization to insect venom is required, the ACE inhibitor must be temporarily replaced with 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 membrane manufacturers instructions).It is necessary to avoid the joint use of ramipril and the use of 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 low-density lipoproteins using dextran sulfate. Therefore, this method should not be used in patients receiving ACE inhibitors.

In patients with impaired hepatic function, the response to drug treatment ramipril can be either strengthened 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.

Monitoring of laboratory parameters before and during drug treatment ramipril (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. Particularly careful monitoring is required for patients with acute and chronic heart failure, renal dysfunction, after kidney transplantation, patients with renovascular disease, including patients with hemodynamically significant unilateral renal artery stenosis in the presence of two kidneys (in such patients, even a slight increase in the serum creatinine concentration may be an index of decreased renal function).

Controlling the concentration of electrolytes

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

Control of hematological parameters (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") . Controlling the number 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 the number of platelets in the peripheral blood.

Determination of the activity of "liver" enzymes, the concentration of bilirubin in the blood

When jaundice or a significant increase in the activity of "hepatic" enzymes, treatment with ramipril should be stopped and medical supervision of the patient should be provided.

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

During drug treatment, it is necessary to refrain from engaging in potentially hazardous activities, including driving, requiring 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, 2.5 mg, 5 mg and 10 mg.

Packaging:

For 7 or 10 tablets in a contour mesh package.

For 1, 2, 3, 4 or 5 contour squares with instructions for use in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004016

Date of registration:12.12.2016

Expiration Date:12.12.2021

The owner of the registration certificate:NANOLEC, LTD. NANOLEC, LTD. Russia

Manufacturer: & nbsp

NANOLEC, LTD. Russia

Farmaktsvet, OOO Russia

Representation: & nbspNANOLEC, LTD.NANOLEC, LTD.

Information update date: & nbsp19.01.2017

Illustrated instructions

Instructions

RAMIPRIL-NANOLEC® (Ramipril-Nanolek)