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

Excipients: microcrystalline cellulose - 27 mg; lactose (tablets-80) - 58.5 mg; silicon dioxide colloid (aerosil) - 0.2 mg; carboxymethyl starch sodium (primogel) - 0.9 mg; magnesium stearate - 0.9 mg.

Composition for a dosage of 5 mg

1 tablet contains:

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

Excipients: microcrystalline cellulose - 40 mg; lactose (tablets-80) - 82.1 mg; silicon dioxide colloid (aerosil) - 0.3 mg; carboxymethyl starch sodium (primogel) - 1.3 mg; magnesium stearate - 1.3 mg.

Composition for a dosage of 10 mg

1 tablet contains:

Active substance: ramipril in terms of 100% substance - 10 mg;

Excipients: cellulose microcrystalline - 50 mg; lactose (tabletol for 80) - 116.2 mg; silicon dioxide colloid (aerosil) - 0.4 mg; carboxymethyl starch sodium (primogel) -1,7 mg; magnesium stearate - 1.7 mg.

Description:

Round flat-cylindrical tablets of white or almost white color with a facet and a risk.

Pharmacotherapeutic group:Angiotensin-converting enzyme (AIP) inhibitor

ATX: & nbsp

C.09.A.A ACE Inhibitors

C.09.A.A.05 Ramipril

Pharmacodynamics:

Ramipril is an inhibitor of long-acting angiotensin-converting enzyme (ACE).

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.

The increased activity of 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. With a decrease in the concentration of angiotensin II in the blood, its inhibiting effect on renin secretion by negative feedback is eliminated, which leads to an increase in renin activity of 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 activity. 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 3-9 hours, and persists for 24 hours. With a 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. A sudden discontinuation of taking the drug does not lead to the development of the "withdrawal" syndrome.

In patients with hypertension ramipril slows the development and progression of myocardial hypertrophy and vascular wall. The drug reduces mortality in the early and distant periods of myocardial infarction, the frequency of repeated heart attacks and the incidence of heart failure. Increases the survival rate and improves the quality of life in patients with chronic heart failure.

Reduces the degree of microalbuminuria (in the initial stage) and the progression of chronic renal failure in patients with severe renal lesions in diabetic nephropathy.

Pharmacokinetics:

After ingestion ramipril quickly absorbed from the gastrointestinal tract, absorption is 50-60%, food intake does not affect the degree of absorption, but slows absorption.

Ramipril is metabolized in the liver, with the formation of an active metabolite - ramiprilat, whose activity is 6 times higher than that of ramipril and inactive diketopiperazine, which is then glucuronized. The maximum concentration of ramipril in the blood serum is reached in 2-4 hours after admission, the equilibrium concentration - by the 4th day of taking the drug.

About 73% of ramipril and 56% of ramiprilate bind to blood plasma proteins. Ramipril and ramiprilate are excreted from the body by the kidneys (about 60%) and through the intestine (about 40%), predominantly in the form of metabolites, less than 2% of the accepted dose is excreted as unchanged ramipril. The half-life for ramipril is 5.1 hours; in the distribution and elimination phase, the drop in the concentration of ramiprilate in the blood serum occurs with a half-life of 3 hours, followed by a transitional phase with a half-life of 15 hours and a prolonged terminal phase with very low plasma ramiprilate concentrations and a half-life of 4-5 days.In chronic renal failure, the elimination half-life increases. If renal function is impaired, excretion of ramipril and its metabolites slows in proportion to a decrease in creatinine clearance (CC).

In patients with liver failure, ramipril metabolism in ramiprilate can be slowed down.

In chronic heart failure, the concentration of ramiprilata increases 1.5-1.8 times.

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.
Chronic heart failure (as part of combination therapy, in particular in combination with diuretics).
Diabetic or nondiabetic nephropathy, preclinical and clinically pronounced stages, including pronounced proteinuria in particular, when combined with arterial hypertension.
Reducing the risk of developing 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 who underwent percutaneous transluminal coronary angioplasty, coronary artery bypass grafting;
- in patients with a history of stroke;
patients with occlusive lesions of peripheral arteries;
- in patients with diabetes mellitus with at least one additional risk factor (microalbuminuria, arterial hypertension,wplasma concentrations of OX, a decrease in plasma concentrations of HDL-C, smoking).
Heart failure, developed during the first few days (from the 2nd to the 9th day) after an acute myocardial infarction.

Contraindications:

increased sensitivity to ramipril and any other component of the drug or other ACE inhibitors;
angioedema (hereditary or idiopathic, as well as in anamnesis, including those associated with previous therapy with ACE inhibitors);
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) or a condition with unstable hemodynamics;
Hemodialysis using high-flow membranes with a negatively charged surface;
severe renal failure (creatinine clearance less than 20 ml / min.);
liver failure;
hemodynamically significant stenosis of the aortic or mitral valve (risk of excessive lowering of blood pressure followed by impaired renal function) or hypertrophic obstructive cardiomyopathy;
primary hyperaldosteronism;
Nephropathy, which is treated with glucocorticosteroids, non-steroidal anti-inflammatory drugs, immunosuppressants and / or other cytotoxic agents;
chronic heart failure in the stage of decompensation;
apheresis of low-density lipoproteins using dextran sulfate;
deficiency of lactase, lactose intolerance, glucose-galactose malabsorption;
hyposensitizing therapy in reactions of hypersensitivity to poisons of insects, such as bees, wasps;
simultaneous application of the drug Ramipril with aliskiren-containing drugs, in patients with diabetes mellitus and renal insufficiency (CC less than 60 ml / min) (see sections "Interaction with other drugs", "Special instructions");
simultaneous use of the drug with angiotensin II receptor antagonists in patients with diabetic nephropathy (see the sections "Interaction with other drugs", "Special instructions");
pregnancy and lactation;
children under 18 years of age (efficacy and safety not established). 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 dangerous (with atherosclerotic lesions of the coronary or cerebral arteries);

conditions accompanied by an increase in the activity of the renin-angiotensin-aldosterone system (RAAS) in which, with ACE inhibition, there is a risk of a sharp drop in blood pressure with impaired renal function: severe arterial hypertension, especially malignant hypertension; chronic heart failure,especially severe or about which other medicines with hypotensive action are taken; hemodynamically significant unilateral stenosis of the renal artery (in the presence of both kidneys); previous intake of diuretics; disturbance of water-electrolyte balance as a result of insufficient intake of liquid and table salt, vomiting, diarrhea, excessive sweating;

impaired liver function;
condition after kidney transplantation;
impaired renal function (creatinine clearance more than 20 ml / min.);
systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma, concomitant therapy with drugs capable of causing changes in the picture of peripheral blood (possibly oppression of bone marrow hematopoiesis, development of neutropenia or agranulocytosis));
diabetes;
elderly age;
hyperkalemia;
hyponatremia (risk of dehydration, arterial hypotension, renal failure);
simultaneous application of the drug Ramipril with angiotensin II receptor antagonists and / or with aliskiren-containing agents in a double blockade of RAAS.

Pregnancy and lactation:

Ramipril is contraindicated in pregnancy and during breastfeeding. Before starting therapy with ramipril, pregnancy should be excluded. Ramipril is not recommended for women planning a pregnancy. In case of pregnancy during drug therapy Ramipril should as soon as possible stop taking the drug and transfer the patient to the reception of other medicines. If drug therapy Ramipril is necessary during breastfeeding, then breastfeeding should be discontinued.

For newborns who have been exposed to intrauterine exposure to ACE inhibitors, careful monitoring is recommended to detect arterial hypotension, oliguria, and hyperkalemia. In oliguria, maintenance of arterial pressure and renal perfusion is necessary by the introduction of appropriate fluids and vasoconstrictors. In newborns and infants, there is a risk of oliguria and neurological disorders, possibly due to a reduction in renal and cerebral blood flow due to a decrease in blood pressure caused by ACE inhibitors (received by pregnant women and after childbirth).Careful observation is recommended.

Dosing and Administration:

Inside, not liquid, squeezed enough liquid, regardless of food intake. Dose of the drug Ramipril should be selected depending on the therapeutic effect and the tolerance of the drug to the patient.

Arterial hypertension: recommended initial dose of the drug Ramipril 2.5 mg per day, once, in the morning or 2 times a day. Depending on the reaction of the patient, the dose can be doubled with a 2-3-week interval. Usually the maintenance dose is 2.5-5 mg per day, the maximum daily dose is 10 mg per day.

Patients taking diuretics should cancel or reduce their dose at least 3 days before the start of the drug Ramipril. The initial daily dose in patients with arterial hypertension who did not have diuretics canceled, or in patients with arterial hypertension and heart failure or renal failure is 1.25 mg (1/2 tablet 2.5 mg) in 1 dose. Treatment should be started under the strict supervision of a physician.

If it is not possible to completely correct the disturbance of the water-electrolyte balance in the case of severe arterial hypertension, as well as for patients,for which the hypotensive reaction represents a certain risk, the initial dose is 1.25 mg (1/2 tablet 2.5 mg).

Chronic heart failure: the recommended initial dose of the drug Ramipril is 1.25 mg (1/2 tablet 2.5 mg) per day in 1 dose. Depending on the reaction of the patient, the dose can be doubled with a 1 -2 week interval. The maximum daily dose is 10 mg.

In patients receiving large doses of diuretics, before starting therapy with the drug Ramipril The dose of diuretics should be reduced.

Heart failure, developed within 2-9 days after acute myocardial infarction: the recommended initial daily dose is 5 mg in two meals in the morning and in the evening at 2.5 mg and rises to 5 mg twice a day (morning and evening) two days later. The usual maintenance dose of the drug Ramipril is 2.5-5 mg twice a day. If the patient does not tolerate the initial dose of the drug (arterial hypotension), it should be reduced to 1.25 mg (1/2 tablet 2.5 mg) twice daily. Two days later the dose can be again increased to 2.5 mg twice a day, after two more days the dose can be increased to 5 mg twice a day. The maximum daily dose should not exceed 10 mg.If the patient does not tolerate increasing the dose to 2.5 mg twice a day, then the drug should be discontinued.

Currently, the experience of treating patients with severe heart failure (III-IV functional class by classification NYE1A), which appeared immediately after an acute myocardial infarction, is insufficient. If such patients decide to undergo treatment with the drug Ramipril, it is recommended that treatment start with the lowest possible dose - 1.25 mg (1/2 tablet 2.5 mg) once a day and special care should be taken with each dose increase. Diabetic nephropathy and nephropathy in the background of chronic diffuse kidney diseases: recommended initial dose of the drug Ramipril is 1.25 mg (1/2 tablet 2.5 mg) once a day. Depending on the tolerability of the patient Ramipril the dose of the drug is further increased: it is recommended to double the dose every 2 weeks to a maintenance dose of 5 mg once a day.

Reducing the risk of developing myocardial infarction, stroke and cardiovascular mortality: recommended initial dose of the drug Ramipril is 2.5 mg once a day. The dose of the drug is then gradually increased, depending on the tolerability of the drug Ramipril: it is recommended to double the dose after 1 week of therapy, and then

in another 2-3 weeks - until reaching the target maintenance dose of 10 mg once a day.

Application of the drug Ramipril in certain groups of patients

Renal insufficiency: with QC less than 30 ml / min, the initial daily dose is 1.25 mg (1/2 tablet 2.5 mg), the maximum daily dose is 5 mg; with QC 30-60 ml / min the initial dose is 2.5 mg, the maximum daily dose is 5 mg; with QC more than 60 ml / min the initial daily dose is from 2.5 mg, the maximum daily dose is 10 mg.

In elderly patients the initial daily dose is 1.25 mg (1/2 tablet 2.5 mg).

Liver failure: the initial recommended dose is 1.25 mg (1/2 tablets 2.5 mg) once a day and the maximum dose is 2.5 mg once a day.

Careful observation of elderly patients (over 65 years old) taking diuretics and patients with chronic heart failure and impaired renal and hepatic function is necessary. The dose of the drug should be selected depending on the target level of blood pressure.

Side effects:

The undesirable effects listed below are given in accordance with the following gradations of their development frequency: very often:> 10%;

often:> 1% - <10%;

infrequently:> 0.1% - <1%;

rarely:>0,01 % - <0,1 %;

Very rarely <0.01%, including individual messages;

the frequency is unknown: according to the available data, it is not possible to establish the frequency of occurrence.

Heart Disease:

Infrequent: 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 decrease in blood pressure, orthostatic hypotension, syncopal conditions (syncope).

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

Rarely: the occurrence or intensification of peripheral circulatory disorders against the background of stenosing vascular lesions, vasculitis.

The frequency is unknown: Raynaud's syndrome.

Disorders from the central nervous system:

Often: headache, a feeling of "lightness" in the head.

Infrequent: dizziness, agevia (loss of taste sensitivity), dysgeusia (a violation of taste sensitivity).

Rarely: tremor, imbalance.

The frequency is unknown: cerebral ischemia, including ischemic stroke and transient impairment of cerebral circulation, impaired psychomotor reactions, paresthesia (burning sensation), parosmia (impaired perception of odors).

Disorders from the side of the organ of vision:

Infrequent: visual disturbances, including blurred image.

Rarely: conjunctivitis.

Hearing impairment:

Rarely: hearing impairment, ringing in the ears.

Disorders from the psyche:

Infrequent: depressed mood, anxiety, nervousness, motor anxiety, sleep disturbances, including drowsiness.

Rarely: confusion.

The frequency is unknown: attention violation.

Disturbances from the respiratory system:

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

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

Disturbances from the digestive tract:

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

Uncommon: pancreatitis, including fatal (cases of pancreatitis with fatal outcome while taking ACE inhibitors have been observed very rarely), increased activity of pancreatic enzymes in the blood plasma, intestinal angioedema, abdominal pain, gastritis, constipation, mucous membrane dryness oral cavity. Rarely: glossitis.

The frequency is unknown: aphthous stomatitis (inflammatory reaction of the oral mucosa).

Disorders from the hepatobiliary system:

Infrequent: increased activity of "hepatic" enzymes and concentration of conjugated bilirubin in the blood plasma.

Rarely: cholestatic jaundice, hepatocellular lesions.

Frequency unknown: acute liver failure, or tsitoliti- cal cholestatic hepatitis (death rarely observed).

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. The frequency is unknown: gynecomastia.

Violations from the 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 the concentration of hemoglobin, thrombocytopenia, and leukocytosis.

The frequency is unknown: oppression of bone marrow hematopoiesis, pancytopenia, hemolytic anemia.

Disturbances from the skin and mucous membranes:

Often: skin rash, in particular maculopapular.

Infrequently: angioedema, including fatal outcome (laryngeal edema can cause airway obstruction leading to death), skin itch, hyperhidrosis.

Rarely: exfoliative dermatitis, urticaria, onycholysis.

Very rarely: photosensitization reactions.

The frequency is unknown: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, psoriasis, psoriasis-like dermatitis, pemphigoid or lichenoid (exocrine) exanthema or enanthema, alopecia.

Disorders from the musculoskeletal system and connective tissue:

Often: muscle cramps, myalgia.

Infrequently: arthralgia.

Disorders from the metabolism, nutrition and laboratory indicators:

Often: increased potassium levels in the blood.

Infrequent: anorexia, decreased appetite.

The frequency is unknown: a decrease in the sodium content in the blood.

Immune system disorders:

The frequency is 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.

Common violations

Often: chest pain, fatigue.

Infrequent: increased body temperature.

Rarely: asthenia (weakness).

Overdose:

Symptoms: a marked decrease in blood pressure, bradycardia, shock, a violation of water-electrolyte balance, acute renal failure, stupor.

Treatment: in mild cases of overdose - gastric lavage, the introduction of adsorbents and sodium picosulphate (preferably within 30 minutes after ingestion). With a marked decrease in blood pressure - the patient should be laid on his back with a low headboard,measures were taken to replenish the volume of circulating blood and normalize the electrolyte balance, and the administration of alpha1-adrenomimetics (norepinephrine, dopamine), if necessary, the volume of circulating blood can be replenished by infusing 0.9% sodium chloride solution; in the case of refractory to medical treatment of bradycardia, it may be necessary to install a temporary artificial pacemaker.

It is necessary to carefully monitor blood pressure, kidney function and the concentration of electrolytes and creatinine in the blood serum. The effectiveness of hemodialysis to eliminate intoxication is not established.

Interaction:

Contraindicated combinations

Application of high-flow dialysis membranes

Risk of development of severe anaphylactic reactions.

Simultaneous use of the drug Ramipril with aliskiren-soderzhaschimi means in patients with diabetes mellitus and renal insufficiency (CC less than 60 ml / min)

The use is contraindicated and not recommended (see the sections "Contraindications", "Special instructions").

Not recommended combinations

With potassium salts, potassium-sparing diuretics (eg, amiloride, triamterene, spironolactone) and other drugs (including angiotensin II receptor antagonists (ARA II), trimethoprim, tacrolimus, cyclosporin) 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 require caution

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

Potentiation of hypotensive effect; when combined with diuretics should monitor the sodium content in the blood serum.

With sleeping pills, narcotic and non-narcotic analgesics Perhaps a more pronounced decrease in blood pressure.
With vasopressor sympathomimetics (epinephrine, dobutamine, dopamine) Reducing the hypotensive effect of ramipril, requires careful monitoring of blood pressure.
With allopurinol, procainamide, cytostatics, immunosuppressants, corticosteroids (systemic glucocorticosteroids) and other agents that can affect hematological parameters

Joint use increases the risk of developing leukopenia.

FROM lithium salts

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

With hypoglycemic agents (insulin, sulfonylurea derivatives, biguanides)

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 their combined use with ACE inhibitors.

FROM glyptines (vildagliptin) and estramustine

With simultaneous use, it is possible to increase the frequency of angioedema development.

Combinations that should be taken into account

With non-steroidal anti-inflammatory drugs (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 serum.

FROM heparin

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

With sodium chloride

Weakening of hypotensive action.

FROM ethanol

Strengthening of vasodilation. Ramipril can enhance the adverse effects of ethanol on the body.

FROM estrogens

Weakening of hypotensive action.

Desensitizing therapy with hypersensitivity to insect venoms ACE inhibitors, including the drug 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.

To the attention of the patient: if you are taking any medications, tell your doctor about it.

Special instructions:

A warning: Patients with hemodynamically significant stenosis of the aortic or mitral valve or any obstruction to outflow from the left ventricle should not apply Ramipril.

Precautions:

At the beginning of treatment, it is necessary to evaluate the kidney function.It is necessary to carefully monitor the kidney function during drug treatment Ramipril, especially in patients with impaired renal function, renal vascular disease (eg, clinically insignificant stenosis of the renal arteries); heart failure.

After taking the first dose, as well as increasing the dose of a diuretic and / or Ramipril, patients should stay for 8 hours under medical supervision to avoid the development of an uncontrolled hypotensive reaction.

In patients with chronic heart failure, taking the drug may lead to the development of severe arterial hypotension, which in some cases is accompanied by oliguria or azotemia and rarely - the development of acute renal failure. Patients with malignant hypertension should begin treatment in a hospital.

Before and during drug treatment Ramipril it is necessary to control blood pressure, kidney function (creatinine, urea), the content of potassium and other electrolytes, hemoglobin, the activity of "liver" transaminases.

The risk of hypersensitivity and allergic-like (anaphylactoid) reactions is increased in patients,simultaneously taking ACE inhibitors and undergoing hemodialysis procedures using dialysis membranes AN69. Similar reactions have been identified in the apheresis of low-density lipoproteins with dextrin sulfate, so the use of this method should be avoided in the treatment of ACE inhibitors.

During treatment with the drug Ramipril in patients with impaired renal function, especially with simultaneous treatment with diuretics, the concentration of urea and creatinine in serum can increase. In this case, treatment should be continued with smaller doses of the drug Ramipril or cancel the drug. In patients with impaired renal function, the risk of hyperkalemia increases.

In patients with impaired liver function due to a decrease in the activity of "liver" transaminases, metabolism of ramipril and the formation of an active metabolite can be slowed. In this regard, the treatment of such patients should be started only under strict medical supervision.

In rare cases, with the use of ACE inhibitors, cholestatic jaundice occurs, with the progression of which fulminant hepatic necrosis develops, sometimes fatal.When jaundice or a significant increase in the activity of "hepatic" transaminases, the drug treatment Ramipril should be discontinued. Care should be taken when prescribing the drug Ramipril patients who are on a low-salt or salt-free diet (an increased risk of developing arterial hypotension). In patients with a reduced volume of circulating blood (as a result of diuretic therapy) during dialysis, with diarrhea and vomiting, symptomatic arterial hypotension may develop.

Transient arterial hypotension is not a contraindication for continuing treatment after stabilizing blood pressure. In the case of repeated occurrence of severe hypotension, the dose should be reduced or the drug should be withdrawn.

Before surgical intervention, including dentistry, it is necessary to warn the surgeon and anesthesiologist about the use of ACE inhibitors, tk. the use of ACE inhibitors in patients undergoing surgery with general anesthesia can lead to a marked decrease in blood pressure, especially with the use of generic anesthetics, which have antihypertensive effects.It is recommended to stop taking ACE inhibitors, including Ramipril, 12 hours before surgery.

In rare cases, during treatment with ACE inhibitors, agranulocytosis, erythrocytopenia, thrombocytopenia, hemoglobinemia or inhibition of bone marrow function are observed. At the beginning and during treatment it is necessary to control the number of white blood cells to detect possible neutropenia / agranulocytosis. More frequent monitoring is recommended in patients with renal insufficiency, with connective tissue diseases (eg, systemic lupus erythematosus or scleroderma) and in patients taking medications that affect hemopoiesis simultaneously (see section "Interactions with other drugs").

Counting blood cells should also be performed if there are clinical signs of neutropenia / agranulocytosis and increased bleeding.

In patients with hypertension in the treatment of the drug Ramipril there is rarely an increase in serum potassium. The risk of hyperkalemia increases with chronic heart failure,simultaneous treatment with potassium-sparing diuretics (spironolactone, amiloride, triamterene) and the administration of potassium preparations.

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 injection of 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 of H1 and H2-histamine receptors), and in the case of inactivation of enzymes C \ -esterase can consider the need to introduce in addition to epinephrine inhibitors of the enzyme C1-esterase.The patient should be hospitalized and followed-up should be carried out until complete relief of symptoms, but not less than 24 hours.

In patients treated with ACE inhibitors, there have been cases of intestinal angioedema, which is manifested by abdominal pain with nausea and vomiting, or without them; 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.

With the use of ACE inhibitors during desensitizing therapy to a wasp or bee venom may arise anaphylactic and anaphylactoid reactions (e.g., hypotension, dyspnea, vomiting, skin rash), which can be life threatening.

Hypersensitivity reactions can occur with insect bites (eg, bees or wasps). When the need for desensitizing treatment (bites) to cancel ACE inhibitors and continue treatment suitable antihypertensive agents from other groups.

Against the background of therapy with an ACE inhibitor, a dry cough may occur, which disappears after the withdrawal of this group. When dry cough occurs, remember the possible association of this symptom with the use of an ACE inhibitor.

Simultaneous use of the drug Ramipril with aliskiren-containing drugs in patients with diabetes mellitus and renal insufficiency (CC less than 60 ml / min) is contraindicated (see the sections "Interaction with other drugs", "Contraindications").

Simultaneous use of the drug with angiotensin II receptor antagonists in patients with diabetic nephropathy is contraindicated (see the sections "Interaction with Other Drugs", "Contraindications"),

Care should be taken when doing physical exercises and in hot weather because of the risk of dehydration and arterial hypotension due to a decrease in fluid volume.

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

During the period of drug treatment Ramipril care must be taken when driving vehicles and engaging in other potentially hazardous activities,(possibly dizziness, especially after the initial dose of the ACE inhibitor in patients taking diuretic medicines, as well as other conditions that may affect the ability to drive vehicles).

Patients are advised to refrain from driving and working with machinery.

Form release / dosage:

Tablets 2.5 mg, 5 mg and 10 mg. For 10 or 14 tablets in a contour mesh package.

3 contour packs of 10 tablets or 1, 2 contour packs of 14 tablets together with instructions for use in a pack of cardboard.

Packaging:

For 10 or 14 tablets in a contour mesh package.

3 contour packs of 10 tablets or 1, 2 contour packs of 14 tablets together with instructions for use in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

2 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002659

Date of registration:14.10.2014

The owner of the registration certificate:TATHIMFARMPREPARATY, JSC TATHIMFARMPREPARATY, JSC Russia

Manufacturer: & nbsp

TATHIMFARMPREPARATY, JSC Russia

Information update date: & nbsp14.10.2014

Illustrated instructions

Instructions

Ramipril® (Ramipril ®)