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

Composition of the capsule (lid): gelatin - 96.5072%, titanium dioxide - 3.2175%, dye brilliant blue - 0.0053%, dye quinoline yellow - 0.0900%, dye crimson [Ponso 4R] - 0,1800%.

Capsules of 10.0 mg:

Active substance: ramipril 10.0 mg;

Excipients: pregelatinized starch - 139.25 mg.

Structure of the capsule (body): gelatin - 99.2608%, titanium dioxide - 0.4388%, dye crimson [Ponso 4R] - 0,0137%, dye diamond brilliant - 0.0090%, dye quinoline yellow - 0.0077%, methylparahydroxybenzoate - 0.1200%, propyl parahydroxybenzoate - 0.0300%, sodium lauryl sulfate - 0.0120%;

Composition of the capsule (lid): gelatin - 96.8728%, titanium dioxide - 2.9250%, dye brilliant blue - 0.0600%, dye quinoline yellow - 0.0510%, dye crimson [Ponso 4R] - 0,0912%.

Composition of black ink: ethanol 29-33%, isopropanol 9-12%, butanol 4-7%, shellac 24-28%, iron dye ferrous oxide 24-28%, ammonia water 1-3%, propylene glycol 0% 5-2%.

Composition of white ink: Shellac 20-25%, ethanol 30-34%, isopropanol 3-6%, butanol 3-6%, propylene glycol 0.5-2%, titanium dioxide 30-34%, polysorbate 80 0- 1%.

Description:

Capsules 2.5 mg: Capsules of the size "4": the lid of pink color, the case of white color, with an inscription MICRO/MICRO black, containing a white powder.

Capsules 5.0 mg: Capsules of size "4": lid of light brown color, body of white color, with an inscription MICRO/MICRO black, containing a white powder.

Capsules 10.0 mg: Capsules of size "4": the lid is dark blue, the body of a gray color, with the inscription MICRO/MICRO black on the body and white on the lid, containing a white powder.

Pharmacotherapeutic group:ACE inhibitor

ATX: & nbsp

C.09.A.A ACE Inhibitors

C.09.A.A.05 Ramipril

Pharmacodynamics:

The active metabolite of ramipril-ramiprilate, formed under the influence of "hepatic" enzymes, is a long-acting inhibitor of the angiotensin-converting enzyme (ACE) (synonyms ACE: kininase II, dipeptidylcarboxydipeptidase I), which is peptidyl dipeptidase. ACE in the blood plasma and tissues catalyzes the conversion of angiotensin I into angiotensin II, which has a vasoconstrictive effect, and the breakdown of bradykinin, which has a vasodilating action. 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 kallikrein-kinin system in blood and tissues causes cardioprotective and endothelioprotective action of ramipril due to activation of the prostaglandin system and, accordingly, an increase in the synthesis of prostaglandins stimulating the formation of nitric oxide 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 potassium content in the blood serum.

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 undesirable phenomena (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 the rate of glomerular filtration.Antihypertensive effect begins to develop 1-2 hours after ingestion of a single dose of the drug, reaching the highest value after 3-9 hours, and persists for 24 hours. At the course of treatment, the antihypertensive effect can gradually increase, usually stabilizing to 3-4 weeks of regular intake 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 (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 taking ramipril slows down speed progression of renal failure and the time of the onset of the terminal stage renal failure and, as a result, reduces the need for hemodialysis or kidney transplant 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 disease due to or vascular lesions (diagnosed coronary heart disease, obliterating peripheral arterial history, history of stroke), or diabetes mellitus with at least one additional risk factor (microalbuminuria, arterial hypertension, increase in total cholesterol concentration, decrease in high density lipoprotein cholesterol concentration , smoking, the addition of ramipril to standard therapy significantly reduces the incidence of myocardial infarction, stroke, and cardiac death but cardiovascular causes. In addition, 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 with clinical manifestations in the first days of acute myocardial infarction (2-9 days) the use of ramipril, started 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 heart failure to severe (III-IV functional class according to NYHA classification) / resistant to therapy (23%), 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%). Simultaneous food intake slows down its absorption, but does not affect the degree 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. All metabolites formed, with the exception of ramiprilate, have no pharmacological activity.

Bioavailability for ramipril after oral administration 2.5-5 mg - 15-28%; for ramiprilate - 45%.

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 ramiprilate in the blood 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 the long-term final phase with a single daily ramipril intake in a dose of 2.5 mg or more,the equilibrium plasma concentration of ramiprilate is reached after approximately 4 days of treatment. With the course use of the drug "effective" T_1/2depending 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.

It is excreted by the kidneys - 60%, through the intestines - 40% (mainly in the form of metabolites).

In case of impaired renal function excretion of ramipril and its metabolites is slowed in proportion to a decrease in creatinine clearance (CC), which leads to an increase in plasma concentrations of ramiprilate, which decreases more slowly than in patients with normal renal function.

When a violation of liver function the conversion into ramiprilat slows down; with chronic heart failure the concentration of ramiprilate and the area under the pharmacokinetic curve "concentration-time" is increased by 1.5-1.8 times.

In healthy elderly volunteers (65-76 years), the pharmacokinetics of ramipril and ramiprilate did not differ significantly from that in young healthy volunteers.

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

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, especially when combined with hypertension.

- Reducing the risk of developing myocardial infarction, stroke, or mortality from cardiovascular causes in patients with high cardiovascular risk:

in patients with confirmed coronary heart disease, myocardial infarction in or without anamnesis, including patients undergoing percutaneous transluminal 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,an increase in plasma concentrations of total cholesterol, a decrease in plasma concentrations of high-density lipoprotein cholesterol, 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;

- angioedema (hereditary or idiopathic, as well as after taking ACE inhibitors) in a history - the risk of rapid angioedema development;

- 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;

- simultaneous use of drugs containing aliskiren, in patients with diabetes mellitus and / or moderate and severe renal insufficiency (creatinine clearance (CK) less than 60 ml / min);

- simultaneous use with angiotensin II receptor antagonists in patients with diabetic nephropathy;

- hemodynamically significant stenosis of the aortic or mitral valve or hypertrophic obstructive cardiomyopathy;

- primary hyperaldosteronism;

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

- hemodialysis (experience of clinical use is insufficient);

- Pregnancy;

- the period of breastfeeding;

- Nephropathy, treatment of which is carried out by glucocorticosteroids, nonsteroidal anti-inflammatory drugs, immunomodulators and / or other cytotoxic agents (see section "Interaction with other drugs");

- chronic heart failure in the stage of decompensation (clinical experience is not enough);

- age under 18 years (effectiveness and safety not established);

- hemodialysis or hemofiltration using some negatively charged membranes, such as high-flux polyacrylonitrile membranes (the risk of developing hypersensitivity reactions) (see "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");

Additional contraindications in the use of the drug Vazolong^® in acute stage of myocardial infarction:

- severe chronic heart failure (functional class IV by classification of NYHA);

- unstable angina;

- life-threatening ventricular arrhythmias;

- "pulmonary" heart.

Carefully:

- Simultaneous use with drugs containing aliskiren, or angiotensin II receptor antagonists (with double blockade of the renin-angiotensin-aldosterone system (RAAS), there is an increased risk of a sharp drop in blood pressure, hyperkalemia, and impaired renal function compared to monotherapy) (see "Specific guidance").

- 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 RAAS, in which, with ACE inhibition, 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 antihypertensive action are taken;
hemodynamically significant unilateral stenosis of the renal artery (in the presence of both kidneys) - in such patients, even a slight increase in serum creatinine concentration may be a manifestation of unilateral impairment of renal function;
previous administration of diuretics;
disturbance of water-electrolyte balance as a result of insufficient intake of liquid and table salt, diarrhea, vomiting, and profuse sweating.

- Dysfunction of the liver (lack of experience of application: it is possible to strengthen and weaken the effects of ramipril, in the presence of patients with cirrhosis of the liver with ascites and edema, significant activation of RAAS is possible, see above "Conditions 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 capable of causing 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 (risk of hyperkalemia).

- Elderly age (risk of increased antihypertensive action).

- Hyperkalemia.

Pregnancy and lactation:

Vazelong^® is contraindicated for use in pregnancy, as it may adversely affect 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 pregnancy during treatment with Vazolong^® should, as soon as possible, stop receiving it and transfer the patient to taking other drugs, in which application the risk for the child will be the least.

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

Dosing and Administration:

Capsules must be swallowed whole, and washed down with a sufficient amount (1/2 cup) of water, regardless of the time of ingestion. The dose is selected depending on the therapeutic effect and the tolerance of the drug to the patient.

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

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

With arterial 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 Vazolong^® 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 drugs, in particular diuretics or blockers of "slow" calcium channels.

With chronic heart failure

The recommended initial dose: 1.25 mg once a day (in this case, it is necessary to apply ramipril in another dosage form - tablets of 2.5 mg with a risk of other manufacturers). 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 divided doses.

The maximum recommended daily dose is 10 mg.

With diabetic or nondiabetic nephropathy

The recommended initial dose: 1.25 mg once a day (in this case, it is necessary to apply ramipril in another dosage form - tablets of 2.5 mg with a risk of other manufacturers). The dose can be increased only 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 is 2.5 mg once a day. Depending on the tolerability of the drug, the patient can gradually increase the dose. It is recommended to double the dose after 1 week of therapy, 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 with clinical manifestations, 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 in the 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 for two days (in this case it is necessary to apply ramipril in another dosage form - tablets of 2.5 mg with a risk of other manufacturers) 2 times a day. Then, depending on the patient's reaction, the dose can be increased. It is recommended that the dose at its increase is doubled with an interval of 1-3 days. Later, the total daily dose, which was initially divided into two doses, can be taken once.

The maximum recommended dose is 10 mg.

Currently, the experience of treating patients with severe chronic 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 Vazolong® therapy, it is recommended that treatment start with the lowest possible dose, 1, 25 mg (in this case, it is necessary to apply ramipril in another dosage form - 2.5 mg tablets with the risk of other manufacturers), and special care should be taken with each dose increase.

Patients with impaired renal function

With SC from 50 to 20 ml / min. at 1.73 m body surface, the initial daily dose is usually 1.25 mg (in this case, it is necessary to apply ramipril in another dosage form - tablets of 2.5 mg with a risk of other manufacturers).The maximum 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 (in this case it is necessary to apply ramipril in another dosage form - tablets of 2.5 mg with a risk of other manufacturers).

Patients with prior diuretic therapy

If possible, diuretics should be canceled within 2-3 days (depending on the duration of diuretics) before starting treatment with Vazolong® or, at the very least, reducing the dose of diuretics taken. Treatment of such patients should start with the lowest dose equal to 1.25 mg of ramipril (in this case, it is necessary to apply ramipril in another dosage form - tablets of 2.5 mg with the risk of other manufacturers), taken once a day, in the morning. After taking the first dose and every time after increasing the dose of ramipril and (or) diuretics, especially "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 (in this case, it is necessary to apply ramipril in another dosage form - tablets of 2.5 mg with a risk of other manufacturers).

Patients with hepatic impairment

The response of blood pressure to taking Vazolong^® can both increase (by slowing the excretion of ramiprilata), and decrease (by slowing the conversion of low-active ramipril to active ramiprilate). Therefore, at the beginning of treatment, careful medical supervision is required. The maximum allowable daily dose is 2.5 mg.

Side effects:

The undesirable effects listed below are given in accordance with the following gradations of their incidence in accordance with the classification of the World Health Organization:

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, heart rhythm disturbances (appearance or gain), palpitations, peripheral edema.

Vascular disorders

Often: excessive decrease in blood pressure, 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, dizziness (a feeling of "lightness" in the head).

Infrequently: vertigo, agevzia, dysgeusia.

Rarely: tremor, imbalance.

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

Disturbances on the part of the organ of sight

Infrequent: visual disturbances, including blurred image.

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.

The frequency is unknown: attention violation.

Disturbances from the respiratory system

Often: "dry" cough (worse at night and in the "lying" position), 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.

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, pain in the upper abdomen, including those associated with gastritis, constipation, dryness of the oral mucosa.

Rarely: glossitis.

Frequency unknown: aphthous stomatitis.

Disturbances from the liver and bile ducts

Infrequently: increased activity of "liver" transaminases and conjugated bilirubin concentration 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: transient impotence due to erectile dysfunction, 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 hemoglobin, thrombocytopenia.

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

Disturbances from the skin

Often: skin rash, in particular maculopapular.

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

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 endocrine system

The frequency is unknown: the syndrome of inadequate secretion of antidiuretic hormone.

Metabolic disorders, nutrition and laboratory indicators

Often: hyperkalemia.

Infrequent: anorexia, decreased appetite.

Frequency unknown: hyponatremia.

Immune system disorders

The frequency is unknown: anaphylactic or anaphylactoid reactions (with the inhibition of ACE, the severity of anaphylactic or anaphylactoid reactions to insect venoms increases)an increase in the titer of antinuclear antibodies.

Common violations

Often: chest pain, increased fatigue.

Infrequent: increased body temperature.

Rarely: asthenia.

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. In the case of a marked decrease in blood pressure to therapy for replenishing the volume of circulating blood and restoring the electrolyte electrolyte balance, an administration of alphaa₁-adrenergic agonists (norepinephrine, dopamine). 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.

Interaction:

Contraindicated combinations

- Use of some high-flow membranes with a negatively charged surface (for example, polyacrylonitrile membranes) during hemodialysis or hemofiltration; use of dextrin sulfate 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 Vazolong® and preparations containing aliskiren

The simultaneous use of Vazolong® and preparations containing aliskiren, in patients with diabetes mellitus or moderate and severe renal failure (CC less than 60 ml / min) is contraindicated and not recommended in other patients(see the sections "Contraindications", "FROM caution "," Special instructions ").

Simultaneous use of Vasolong® and angiotensin II receptor antagonists (ARA II)

The simultaneous use of the drug Vazolong® and ARA II is contraindicated in patients with diabetic nephropathy and is not recommended in other patients (see the sections "Contraindications", "With caution", "Special instructions").

Unrecommended combinations

- With potassium salts, potassium-sparing diuretics (for example, spironolactone, eplerenone, amiloride, triamterene), other drugs capable of increasing the serum potassium content (including APA II, tacrolimus, ciclosporin; trimethoprim, sulfamethoxazole, which are part of co-trimoxazole (a combined antibacterial agent containing sulfamethoxazole and trimethoprim))

Possible to increase the content of potassium in the serum, sometimes significantly expressed (while the application requires careful control of potassium in blood serum).

Combinations, which should be used with caution

- With antihypertensive drugs (especially diuretics) and other drugs that lower blood pressure (nitrates, tricyclic antidepressants, general anesthetics, baclofen, alfuzosin, doxazosin, prazosin, tamsulosin, terazosin)

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

- With sleeping pills, narcotic and anesthetics

Perhaps a more pronounced decrease in blood pressure.

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

Reduction of antihypertensive action of ramipril requires careful monitoring of blood pressure.

- With allopurinol, procainamide, cytostatics, immunosuppressants, corticosteroids (glucocorticosteroids and mineralokortikosteroidami) and other agents that may affect the haematological

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

- With lithium salts

Increased serum lithium concentration and increased cardio- and neurotoxic effects of lithium. Therefore, the content of lithium in the blood serum should be monitored.

- FROM hypoglycemic agents for oral administration (sulfonylurea derivatives, biguanides), insulin

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 the blood glucose concentration be carefully controlled at the beginning of their simultaneous use with ACE inhibitors.

- With vildagliptin, other glyptins and estramustine

Increased incidence of angioedema.

- FROM inhibitors mTOR (mammalion Target of Rapamycin - a target of rapamycin in mammalian cells), for example, tessirolimus

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

Combinations, which should be taken into account

- With non-steroidal anti-inflammatory drugs (indomethacin, acetylsalicylic acid (more than 3 g / day))

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.

- With sodium chloride

Weakening of antihypertensive action of ramipril and less effective treatment of symptoms of chronic heart failure.

- FROM ethanol

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

- With estrogens

Weakening of antihypertensive action 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.

It is assumed that similar reactions are possible when other allergens are used.

Special instructions:

Before starting treatment with Vazolong^® 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 taking Vazolong® (in this case, carefully monitor the condition of patients with chronic heart failure, due to the possibility of developing them decompensation due to increased 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 Vazolong® 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 blood pressure lowering (see "With caution") .

With malignant arterial hypertension and heart failure, especially in the acute stage of myocardial infarction, treatment with Vazolong® 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 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 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 Vazolong^® 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.

Simultaneous use of Vazolong® with preparations containing aliskiren, or with ARA II, resulting in a double blockade of RAAS, is not recommended due to the risk of excessive reduction in blood pressure, the development of hyperkalemia and impaired renal function compared to monotherapy. Simultaneous use of Vazolong® with preparations containing aliskiren, in patients with diabetes mellitus and / or moderate or severe renal failure (CC less than 60 ml / min) is contraindicated (see the sections "Contraindications", "Interaction with other drugs").

The simultaneous use of ARA II in patients with diabetic nephropathy is contraindicated (see the sections "Contraindications", "Interaction with other drugs").

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 (adrenaline) (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 enzyme inactivators C₁- esterases, we can consider the need to introduce in addition to epinephrine (adrenaline) 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 the patient appears on the background of treatment with ACE inhibitorsthe above-described symptoms should be considered in the differential diagnosis and the possibility of developing an intestinal angioedema.

Treatment aimed at desensitization to insect venoms (such as 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 the appropriate drug of the other group.

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 (eg, polyacrylonitrile membranes) (see also membrane manufacturers instructions).It is necessary to avoid joint use of Vazolong® and such membranes, for example, for urgent hemodialysis or hemofiltration. In this case, it is preferable to use other types of membranes or stop taking 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 Vazolong® can be either increased or decreased. 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 dentistry), it is necessary to alert the surgeon / anesthesiologist about the use of ACE inhibitors.

It is recommended to carefully monitor newborns who have undergone 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 decrease in renal and cerebral blood flow due to a decrease in blood pressure caused by ACE inhibitors.

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

Control of kidney function (determination of creatinine concentration)

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, 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 creatinine concentration may be an indicator decrease in kidney function).

Control of the content 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, number of leukocytes, erythrocytes, platelets, leukocyte formula)

It is recommended to monitor the parameters of a general blood test to detect possible leukopenia. More regular monitoring is recommended at the beginning of treatment and in patients with impaired renal function, as well as in patients with connective tissue diseases or in patients receiving concomitantly other drugs capable of altering the picture of peripheral blood (see 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.

When jaundice or a significant increase in the activity of "liver" transaminases, treatment with Vazolong® should be stopped and medical supervision of the patient should be provided.

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

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions (possibly dizziness, especially after the initial dose of an ACE inhibitor in patients taking diuretic drugs).

Form release / dosage:

Capsules, 2.5 mg, 5.0 mg and 10.0 mg.

Packaging:

10 capsules in an Al / Al strip.

By 3, 5 or 10 strips together with instructions for use in cardboard pack.

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 the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:PL-000967

Date of registration:18.10.2011 / 19.10.2016

Expiration Date:Unlimited

The owner of the registration certificate:Micro Labs LimitedMicro Labs Limited India

Manufacturer: & nbsp

MICRO LABS, Limited India

Representation: & nbspMICRO LABS LIMITED MICRO LABS LIMITED India

Information update date: & nbsp05.02.2017

Illustrated instructions

Instructions

Vazolong® (Vasolong®)