Ramipril-SZ - instructions for use, doses, side effects, contraindications

Formed under the influence of "liver" enzymes, the active metabolite ramipril - ramiprilat is a long-acting ACE inhibitor, which is peptidyl dipeptidase. 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 (NO) 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 serum potassium ion content.

By reducing the concentration of angiotensin II eliminates its inhibitory effect on the secretion of renin by the type of negative feedback in the blood, which leads to an increase in plasma renin activity. 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 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. 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 use of ramipril slows the rate of progression of renal failure and the time of the onset of the terminal stage of renal failure and, as a result, reduces the need for hemodialysis procedures or

kidney transplantation. 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 or vascular lesions (diagnosed coronary heart disease, obliterating diseases of the peripheral arteries in the anamnesis, a stroke in the anamnesis),or diabetes mellitus with at least one additional risk factor (microalbuminuria, hypertension, increase in total cholesterol concentrations, decrease in high density lipoprotein (HDL-C) cholesterol concentrations, smoking), ramipril addition 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 the death rate decreases (by 27 %), risk of sudden death (by 30 %), risk of progression of chronic heart failure to severe (III-IV functional class by classification NYHA) / 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, 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 ranges from 15% (for a dose of 2.5 mg) to 28 % (for a dose of 5 mg). Bioavailability of the active metabolite - ramiprilata - after ingestion of 2.5 mg and 5 mg 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 the plasma concentration of ramiprilata occurs in several stages: the phase of distribution and excretion with a half-life (Tm) of ramiprilata, which is approximately 3 hours, then the intermediate phase with T1/2 ramiprilata for about 15 hours and a final phase with a very low concentration of ramiprilate in the blood plasma and T 1/2 ramiprilata, 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 the long-term final phase with ramipril alone for a day at a dose 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.

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

After ingestion of a radiolabelled ramipril (10 mg), 39% of the radioactivity is excreted through the intestine and about 60 % - the kidneys. 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 to 90% of metabolites in urine and bile were identified as ramiprilate and metabolites of ramiprilate. Ramipril glucuronide and ramipril diketopiperazine are approximately 10 to 20 % of the total, and the urinary content of non-metabolized ramipril is approximately 2%.

In animal studies, it was shown that ramipril It is secreted with breast milk.

For violations of kidney function with creatinine clearance (CC) less than 60 ml / min. the 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 a two-week treatment with ramipril 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 to 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:

Essential 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 those with pronounced proteinuria, especially when combined with 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 undergoing percutaneous transluminal coronary angioplasty, coronary artery bypass grafting;
in patients with a history of stroke;
in patients with occlusive lesions of peripheral arteries;
in patients with diabetes mellitus with at least one additional risk factor (microalbuminuria, arterial hypertension, increased plasma concentrations of OX, decreased plasma concentrations of cholesterol-HDL, smoking).

Heart failure, which developed during the first few days (from 2 to 9 days) after 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.or a condition with unstable hemodynamic parameters.
Hemodynamically significant stenosis of the aortic or mitral valve or hypertrophic obstructive cardiomyopathy (GOKMP).
Primary hyperaldosteronism.
Severe renal failure (CC less than 20 ml / min with a body surface of 1.73 m²) (experience of clinical use is insufficient).
Pregnancy.
Lactation period.
Nephropathy, which is treated with glucocorticosteroids, non-steroidal anti-inflammatory drugs, immunomodulators and / or other cytotoxic agents (clinical experience

application is insufficient, 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 (clinical experience is insufficient).
Hemodialysis (clinical experience is not enough).

Hemodialysis or hemofiltration using some membranes with a negatively charged surface, such as high-flux membranes from polyacrylonitrile (the risk of developing hypersensitivity reactions) (see.sections "Interactions with other medicines", "Special instructions").

Lysis of low density lipoproteins using dextran sulfate (the risk of developing hypersensitivity reactions) (see section Special instructions).
Desensitizing therapy in reactions of hypersensitivity to poisonous insects, such as bees, wasps (see section "Special instructions").

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 an increase in the activity of the renin-angiotensin-aldosterone system (RAAS), in which, when ANP is inhibited, 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;
disturbance of water-electrolyte balance as a result of insufficient intake of liquid and table salt, diarrhea, vomiting, abundant sweating.
- Dysfunction of the liver (insufficiency of the experience of application: it is possible to strengthen and weaken the effects of ramipril, in the presence of cirrhosis of the liver with ascites and edema, a significant activation of RAAS is possible, see above the states accompanied by increased activity of RAAS).
- Dysfunction of the kidneys (QC more than 20 ml / min with a body surface of 1.73 m²) because of the risk of developing hyperkalemia and leukopenia).
- Condition after kidney transplantation.
- Systemic diseases of connective tissue, 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 Interactions with other medicinal products
0, by means).
- Diabetes mellitus (risk of hyperkalemia).
- Elderly age (risk of increased hypotensive effect).
- Hyperkalemia.

Pregnancy and lactation:

Ramipril-SZ is contraindicated in pregnancy, as it can have an adverse effect on the fetus: impairment of fetal kidney development, fetal and neonatal fetal decline, renal dysfunction, hyperkalaemia, skull bones hypoplasia, oligohydramnia, 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 diagnosing pregnancy during treatment with Ramipril-SZ, 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 Ramipril-C3 is necessary during breastfeeding, then breastfeeding should be discontinued.

Dosing and Administration:

Tablets must be swallowed whole (do not chew),and drink a sufficient amount (1/2 cup) of water, regardless of food intake (that is, tablets can be taken as before, and during or after meals). The dose is selected depending on the therapeutic effect and the tolerance of the drug to the patient.

Treatment with Ramipril-SZ usually is 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 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 once a day (1/2 tablet 2.5 mg). Depending on the patient's response 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 given 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: 1.25 mg once a day (1/2 tablet 2.5 mg). The dose can be increased to 5 mg once a day. At these conditions, doses above 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.

With heart failure, 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 (1/2 tablet 2.5 mg).

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 appeared immediately after an acute myocardial infarction, is insufficient. If such patients decide to take Ramipril-SZ treatment,it is recommended that the treatment start with the lowest possible dose - 1.25 mg once a day (1/2 tablet 2.5 mg) and special care should be taken with each dose increase.

Application of Ramipril-SZ in selected groups of patients

Patients with impaired renal function

With SC from 50 to 20 ml / min at 1.73 m² body surface, the initial daily dose is usually 1.25 mg (1/2 tablet 2.5 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 / day (1/2 tablet 2.5 mg).

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-SZ, or at least reduce the dose of diuretics taken. Treatment of these patients should begin with the lowest dose of 1.25 mg of ramipril (1/2 tablet 2.5 mg) 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 (1/2 tablet 2.5 mg). Patients with hepatic impairment

The BP response to Ramipril-S3 can both increase (by slowing the elimination 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:

Classification of the incidence of adverse events (WHO):

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 pectoris 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: the "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.

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).

Disturbances on the part of the organ of sight

Infrequent: visual disorders, including blurred vision.

Rarely: conjunctivitis.

Hearing disorders Rarely: hearing impairment, ringing in the ears.

Disorders from the psyche

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

Rarely: confusion.

Frequency unknown: violation of attention.

Disturbances from the respiratory system

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

Infrequent: bronchospasm, including exacerbation 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.

Infrequently: pancreatitis, including fatal cases (cases of pancreatitis with fatal outcome with the intake of ACE inhibitors were very rare), increased activity of pancreatic enzymes in the blood plasma, intestinal angioedema, abdominal pain, gastritis, constipation, dryness of the mucosa oral cavity

Rarely: glossitis

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

Disorders from the hepatobiliary system

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

Rarely: cholestatic jaundice, hepatocellular lesions.

The frequency is unknown: acute liver failure, 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: erectile dysfunction with transient impotence, decreased libido.

The frequency is 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.

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

Disturbances from the skin and mucous membranes

Often: skin rash, in particular maculopapular.

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

Rarely: exfoliative dermatitis, urticaria, onycholysis.

Very rarely: photosensitization reactions,

The frequency is unknown: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, exacerbation of psoriasis, psoriasis-like dermatitis, pemphigoid or lichenoid (lichen) 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.

Unknown frequency: 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 titer of antinuclear antibodies.

Common violations

Often: chest pain, fatigue.

Infrequent: increased body temperature.

Rarely: asthenia (weakness).

With simultaneous use of ACE inhibitors and preparations of gold (sodium aurotomy malate) for intravenous administration, a symptom complex including facial flushing, nausea, vomiting and arterial hypotension is described.

With the use of ACE inhibitors, the development of a symptom complex including fever, myalgia, arthralgia, serositis, vasculitis, an increase in ESR, leukocytosis, eosinophilia, skin rash, a positive test for antinuclear antibodies is possible.

With the use of ACE inhibitors, the development of the syndrome of insufficient secretion of antidiuretic hormone is possible.

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, intake of adsorbents, sodium sulfate (if possible within the first 30 minutes). In the case of a pronounced reduction in blood pressure to therapy to replenish the volume of circulating blood and restore the electrolyte balance, the administration of alpha-adrenergic agonists (norepinephrine, dopamine). In the case of refractory to medical treatment of bradycardia, it may be necessary to install a temporary artificial driverrhythm. 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 low density lipoproteins

Risk of development of severe anaphylactic reactions.

Not recommended combinations

With potassium salts, potassium-sparing diuretics (for example, amiloride, triamterene, spironolactone)

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 (especially diuretics) and other drugs that reduce blood pressure (nitrates, tricyclic antidepressants)

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)

Reducing the hypotensive effect of ramipril, careful monitoring of blood pressure is required.

With allopurinol, procainamide, cytostatics, immunosuppressants, systemic glucocorticosteroids and other agents that can affect hematological parameters

Joint use increases the risk of developing leukopenia.

With lithium salts

Increased serum lithium concentration and increased cardio- and neurotoxic effects of lithium.

With hypoglycemic agents for oral administration (derivatives of sulfonylureas, biguanides), insulin

In connection with a decrease in insulin resistance under the influence of ramipril, it is possible to increase the hypoglycemic effect of these drugs right up to the development of hypoglycemia.

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.

With heparin

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

FROM sodium chloride

Weakening of the hypotensive effect of ramipril and less effective treatment of symptoms of chronic heart failure.

FROM ethanol

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

With estrogens

Weakening of the hypotensive effect of ramipril (fluid retention).

Desensitizing therapy with hypersensitivity to insect venoms

ACE inhibitors, including ramipril, increase the likelihood of developing severe anaphylactic or anaphylactoid reactions to insect venoms.

With simultaneous use of ACE inhibitors and preparations of gold (sodium aurotomy malate) for intravenous administration, a symptom complex including facial flushing, nausea, vomiting and arterial hypotension is described.

Special instructions:

Before starting treatment with the drug Ramipril-SZ, it is necessary to eliminate hyponatremia and hypovolemia. In patients who have been taking diuretics, it is necessary to cancel them, or at least reduce their dose 2-3 days before the start of the drug Ramipril-SZ (in this case, the condition of patients with chronic cardiacinsufficiency, in connection with the possibility of developing their decompensation due to an increase in the 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 Ramipril-S3 is used for the first time or at 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 BP reduction (see "With caution" ).

With malignant arterial hypertension and heart failure, especially in the acute stage of myocardial infarction, treatment with Ramipril-SZ should begin 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 reduction 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 due to 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 sodium content in the blood.

During treatment with the drug Ramipril-SZ 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 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 Hp and Hg-histamine receptors), and in case of inactivation of enzyme Inactivators C i-esterase can consider the need to introduce in addition to epinephrine inhibitors of the enzyme C _t-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 should be temporarily replaced by a corresponding drug of another class.

With the use of ACE inhibitors, life-threatening,

rapidly developing anaphylactoid reactions, sometimes up to the development of shock during hemodialysis or plasma filtration using certain high-flow membranes (for example, polyacrylonitrile membranes) (see also the instructions of membrane manufacturers).It is necessary to avoid the joint use of Ramipril-C3 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 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 treatment with Ramipril-C3 can be either enhanced 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 newborns there is a risk of oliguria and neurological disorders, possibly due to lower renal and cerebral blood flow due to the reduction in blood pressure caused by ACE inhibitors.

Monitoring of laboratory parameters before and during treatment with Ramipril-NW (up to 1 times per month in the first Z-b 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 (hemoglobin concentration, number of leukocytes, erythrocytes, platelets, leukocyte formula)

It is recommended to monitor the parameters of the general blood test, to identify 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, and also 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 significant increase in the activity of "liver" enzymes, treatment with Ramipril-SZ should be stopped and medical supervision of the patient should be provided.

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

During the period of treatment with Ramipril-SZ, it is necessary to refrain from engaging in potentially dangerous activities, including driving a vehicle 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, 10 mg.

For 10 or 14 tablets in a contour mesh package.For 28, 30 or 90 tablets in a can of polymer or a bottle of polymer. Each can or bottle, 3, 6, 9 contour cell packs of 10 tablets or 1, 2, 3, 4 contour packs of 14 tablets, together with the instructions for use, are placed in a pack of cardboard.

Packaging:For 10 or 14 tablets in a contour mesh package. For 28, 30 or 90 tablets in a can of polymer or a bottle of polymer. Each can or bottle, 3, 6, 9 contour cell packs of 10 tablets or 1, 2, 3, 4 contour packs of 14 tablets, together with the instructions for use, are placed in a pack of cardboard.

Storage conditions:

In a dry, 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 printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001971

Date of registration:17.01.2013

The owner of the registration certificate:NORTH STAR, CJSC NORTH STAR, CJSC Russia

Manufacturer: & nbsp

NORTH STAR, CJSC Russia

Information update date: & nbsp06.08.2013

Illustrated instructions

Instructions

Ramipril-SZ ® (Ramipril-SZ ®)