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

One capsule contains active substance ramipril 0.010 g, Excipients: lactose monohydrate 0.1355 g, silicon colloidal dioxide 0.0030 g, calcium stearate 0.0015 g and capsules, hard gelatinous: titanium dioxide - 2%, gelatin - up to 100%.

Description:

Hard gelatin capsules No. 3 in white. The contents of the capsules are a powder or compacted mass of white or almost white color, disintegrating when pressed with a glass rod.

Pharmacotherapeutic group:inhibitor of angiotensin-converting enzyme (ACE).

ATX: & nbsp

C.09.A.A ACE Inhibitors

C.09.A.A.05 Ramipril

Pharmacodynamics:

Ramipril inhibits angiotensin-converting enzyme (ACE), blocks the conversion of angiotensin I in angiotensin II, as a result of which (regardless of renin plasma activity) an antihypertensive effect develops (in the "lying" and "standing" position) without a compensatory increase in the heart rate (HR). Reduces the production of aldosterone.

Reduces overall peripheral vascular resistance (OPSS) or postnagruzku, pressure in the pulmonary capillaries (preload), resistance in the pulmonary vessels; increases the minute volume of blood and tolerance to the load. With prolonged use promotes the reverse development of myocardial hypertrophy in patients with arterial hypertension. Reduces the frequency of arrhythmias in myocardial reperfusion; improves the blood supply of the ischemic myocardium; prevents changes in the vascular endothelium caused by a high-cholesterol diet.

Strengthens coronary and renal blood flow.

The onset of antihypertensive action is 1.5 hours after ingestion, the maximum effect is 5-9 hours, the duration of action is 24 hours. There is no "cancellation" syndrome.

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

With diabetic and nondiabetic nephropathy the administration of ramipril slows the rate of progression of renal failure and the time of the onset of the terminal stage of renal insufficiency and, as a result, reduces the need for hemodialysis or kidney transplantation. At the initial stages of diabetic or nondiabetic nephropathy ramipril reduces the severity of albuminuria.

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.

In the liver, it is metabolized to form an active metabolite of ramiprilate (6 times more active inhibits ACE than ramipril) and inactive metabolites - diketopiperazine ester, diketopiperazic acid, as well as ramipril glucuronide and ramiprilate. All metabolites formed, with the exception of ramiprilate, have no pharmacological activity. The connection with blood plasma proteins for ramipril - 73%, ramiprilata - 56%.

After taking ramipril inside, the maximum plasma concentrations of ramipril and ramiprilata are reached after 1 and 2-4 hours, respectively.

Bioavailability for ramipril after oral administration 2.5-5 mg - 15-28%; for ramiprilate - 45%. After a daily intake of 5 mg / day, the stable concentration of ramiprilate in blood plasma is reached by day 4. The half-life (Tc) for ramipril is 5.1 hours; in the distribution and elimination phase, a decrease in serum ramiprilate concentration occurs with Tg equal to 3 hours, followed by a transition phase with T1 / 2 equal to 15 hours and a prolonged terminal phase with very low plasma ramiprilat concentrations and T1 / 2 of 4-5 days . T1 / 2 increases with chronic renal failure (CRF). The volume of distribution of ramipril - 90 liters, ramiprilata - 500 liters. It is excreted by the kidneys - 60%, through the intestines - 40% (mainly in the form of metabolites).If renal function is impaired, excretion of ramipril and its metabolites slows in proportion to a decrease in creatinine clearance (CC); when the liver function is impaired, transformation into ramiprilat is slowed down; with heart failure, the concentration of ramiprilate 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:

essential hypertension;
chronic heart failure (as part of combination therapy, in particular, in combination with diuretics);
diabetic or nondiabetic nephropathy, preclinical or clinically pronounced stages, including those with pronounced proteinuria, especially when combined with hypertension;
reduction in the risk of myocardial infarction, stroke, or cardiovascular mortality in patients with high cardiovascular risk:

o in patients with confirmed coronary heart disease, myocardial infarction in or without anamnesis, including patients undergoing percutaneous transluminal coronary angioplasty, coronary artery bypass grafting,

o in patients with a history of stroke,

o in patients with occlusive lesions of peripheral arteries,

o in patients with diabetes mellitus with at least one additional risk factor (microalbuminuria, arterial hypertension, increased plasma concentrations of OX, lower plasma concentrations of HDL-C, smoking);

heart failure, developed during the first few days (from the second to the ninth day) after acute myocardial infarction (see the section "Pharmacodynamics").

Contraindications:

increased sensitivity 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 angioedema development;
hemodynamically significant stenosis of the renal arteries (bilateral or unilateral in the case of a single kidney);
arterial hypotension (systolic blood pressure (BP) less than 90 mm Hg) or a condition with unstable hemodynamics;
hemodynamically significant stenosis of the aortic or mitral valve or hypertrophic obstructive cardiomyopathy (GOKMP);
primary hyperaldosteronism;
severe renal failure (creatinine clearance (CC) less than 20 ml / min with body surface 1.73 m2);
hemodialysis;
pregnancy, lactation;
naveropathy, the treatment of which is carried out by glucocorticosteroids, nonsteroidal
immunomodulators and / or other cytotoxic agents (see section "Interaction with other drugs");
simultaneous use of drugs containing aliskiren, in patients with diabetes mellitus and in patients with renal insufficiency (creatinine clearance less than 60 ml / min).
lactose intolerance, lactase deficiency, glucose-galactose malabsorption;
conducting desensitizing therapy in reactions of hypersensitivity to poisons of Hymenoptera insects such as bees, wasps;
apheresis of low-density lipoproteins using dextrin sulfate (the risk of developing hypersensitivity reactions);
age under 18 years of age (safety and efficacy not studied);
chronic heart failure in the stage of decompensation (clinical experience is not enough);

Additional contraindications for the use of Dilaprel ® in the acute stage of myocardial infarction

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

Carefully:

conditions in which excessive reduction in blood pressure is particularly dangerous (with atherosclerotic lesions of the coronary and cerebral arteries);
states, accompanied by an increase in the activity of the renin-angiotensin-aldosterone system (RAAS), in which, with the inhibition of ACE, there is a risk of a sharp decrease in blood pressure with impaired renal function:
severe arterial hypertension, especially malignant hypertension,
chronic heart failure, especially severe or about which other drugs with antihypertensive action are taken,
hemodynamically significant unilateral stenosis of the renal artery (in the presence of both kidneys),
previous administration of diuretics,
disturbance of water-electrolyte balance as a result of insufficient intake of liquid and table salt, diarrhea, vomiting, profuse sweating;
impaired liver function (insufficient experience of application: it is possible both to enhance 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 "states accompanied by increased activity of RAAS");
diabetes mellitus (risk of hyperkalemia);
renal dysfunction (KC more than 20 ml / min at body surface 1.73 m2) (risk of hyperkalemia and leukopenia);
condition after kidney transplantation;
systemic connective tissue diseases, incl. systemic lupus erythematosus, systemic scleroderma, concomitant therapy with myelotoxic drugs, capable of causing changes in picture of peripheral blood (possibly oppression of bone marrow hematopoiesis, development of neutropenia or agranulocytosis);
- old age (risk of increased antihypertensive effect);
- hyperkalemia.

Pregnancy and lactation:

Dilaprel® should not be used during pregnancy. Therefore, before starting treatment, you should make sure that there is no pregnancy. If the patient becomes pregnant during the treatment period, it is necessary to replace the drug therapy with Dilaprel ® as soon as possible with another therapy.Otherwise, there is a risk of impaired fetal kidney development, fetal and newborn blood pressure lowering, renal dysfunction, hyperkalemia, skull bones hypoplasia, oligohydramnion, limb contracture, skull deformity, lung hypoplasia, especially in the first trimester of pregnancy.

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 blood pressure and renal perfusion by replenishing the volume of circulating blood and vasoconstrictor. In newborns, there is a risk of 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 (received by pregnant women and after childbirth).

In animal studies, it was shown that ramipril is allocated with milk l of activating animals.

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

Dosing and Administration:

To ensure the following dosage regimen, it is necessary to use the preparation of ramipril in another dosage form: 2.5 mg tablets with a risk (for a dose of 1.25 mg), and capsules or tablets 2.5 mg and 5 mg.

Capsules must be swallowed whole and washed down with a sufficient amount (1/2 cup) of water, regardless of food intake (ie capsules may be taken before, during or after meals). Dose is selected depending on the therapeutic effect and tolerability of the drug to patients.

Arterial hypertension Inside, the initial dose is 2.5 mg, once, 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 may be increased to 5 mg of Dilaprel ® 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 an insufficient antihypertensive effect 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.

Chronic heart failure The initial dose is 1.25 mg / day. Depending on the patient's reaction to the therapy, the dose can be increased. It is recommended to double it at intervals of 1-2 weeks. Doses of 2.5 mg or more should be taken once or divided into 2 divided doses. The maximum daily dose is 10 mg.

With heart failure, developed during the first few days (from the second to the ninth day) after an acute myocardial infarction

The initial dose is 5 mg divided into 2 divided doses, 2.5 mg each morning and evening. If the patient does not tolerate this initial dose (there is an excessive decrease in blood pressure), then it is recommended to give 1.25 mg twice a day for two days. Then, depending on the patient's reaction, the dose can be increased. It is recommended that the dose at its increase is doubled with an interval of 1-3 days. Later, the frequency of daily intake can be reduced to 1 time per day.

The maximum recommended daily dose is 10 mg.

Currently, the experience of treating patients with severe chronic heart failure (III-IV functional class by classification of NYHA), immediately after immediately after an acute myocardial infarction, is inadequate.

If such patients decide to undergo treatment with Dilasprel, it is recommended that the treatment start with the lowest possible dose, 1.25 mg once a day. Special care should be taken with each dose increase.

With diabetic or nondiabetic nephropathy

The initial dose is 1.25 mg once a day.

The dose can be increased to 5 mg once a day.

The maximum daily dose is 5 mg. Use of the drug Dilaprel® in specific patient groups

Patients with impaired renal function When creatinine clearance is more than 60 ml / min, the maximum daily dose is 10 mg; at the clearance of creatinine from 30 to 60 ml / min the maximum daily dose is 5 mg; when the creatinine clearance is less than 30 ml / min, the initial dose is not more than 1.25 mg, the maximum daily dose is 5 mg; in patients on hemodialysis, the initial dose is 1.25 mg, the maximum daily dose is 5 mg.

Patients with incompletely adjusted water-electrolyte balance, patients with severe arterial hypertension, as well as patients for whom an excessive decrease in blood pressure poses a certain risk (for example, in severe atherosclerotic coronary and cerebral arteries)

The initial dose is reduced to 1.25 mg / day.

Patients with prior diuretic therapy

It is necessary, if possible, to cancel diuretics for 2-3 days (depending on the duration of the action of diuretics) before starting treatment with the drug Dilaprel, or at least reduce the dose of diuretics taken. Treatment of these patients should begin with the lowest dose, equal to 1.25 mg of ramipril, taken 1 time per 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 1.25 mg.

Patients with hepatic impairment The reaction of blood pressure to the preparation of Dilasprel® can both be enhanced (by slowing the elimination of ramiprilate) and decrease (by slowing the conversion of ramipril to ramiprilate). Therefore, at the beginning of treatment, careful medical supervision is required.

The maximum allowable daily dose is 2.5 mg.

Side effects:

The following are undesirable

Effects are given in accordance with

the following gradations of their frequency I

occurrence:

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.

From the cardiovascular sideuemewe:

often - excessive reduction of blood pressure, orthostatic hypotension, syncopal conditions, chest pain;

infrequently - myocardial ischemia, including the development of an attack of angina or infarction myocardium, tachycardia, arrhythmia (appearance or exacerbation), palpitations, peripheral edema, "tides" of blood to the skin of the face.

From the genitourinary system:

infringement of function of kidneys, including development of an acute renal failure, increase in quantity of the allocated urine, strengthening of existing proteinuria, increase in concentration of urea and a creatinine in blood, transient impotence due to erectile dysfunction, a decrease in libido; frequency unknown - gynecomastia.

From the central nervous system:

often - headache, a feeling of "lightness" in the head, a feeling of fatigue;

infrequent - dizziness, agevia (loss of taste sensitivity), dysgeusia (a violation of taste sensitivity), depressed mood, anxiety, increased excitability, motor anxiety, sleep disturbances, including drowsiness;

rarely - tremor, the development or enhancement of circulatory disorders against the background of stenosing vascular lesions, vasculitis, asthenia, imbalance, confusion.

frequency is unknown - Reynaud's syndrome, cerebral ischemia, including ischemic stroke and transient cerebral blood flow disorder, psychomotor reactions, paresthesia (burning sensation), parosmia (impaired perception of odors), attention impairment, depression.

From the sense organs:

infrequent - visual disturbances, including blurred vision;

rarely - conjunctivitis, hearing impairment, tinnitus;

From the musculoskeletal system: often - muscle cramps, myalgia; infrequently - arthralgia.

From the digestive system:

often - inflammatory reactions in the stomach and intestines, digestive disorders, discomfort in the abdomen, dyspepsia, diarrhea, nausea, vomiting; infrequently - pancreatitis, including fatal outcome, increased activity of pancreatic enzymes in the blood plasma, intestinal angioedema, abdominal pain, gastritis, constipation, dryness of the oral mucosa, increased activity of "hepatic" enzymes and conjugated bilirubin concentration in blood plasma, anorexia, decreased appetite;

rarely - glossitis, cholestatic jaundice, hepatocellular lesions; frequency unknown - aphthous stomatitis, acute hepatic insufficiency, cholestatic or cytolytic hepatitis (lethal outcome was observed extremely rarely).

From the skin:

often - skin rash, in particular maculopapular;

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

rarely - exfoliative dermatitis, urticaria, onycholysis;

very rarely photosensitization reactions;

frequency is unknown - toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, weighting flow psoriasis, psoriasiform dermatitis, pemfigoidnaya or lichenoid (lishaevidnaya) exanthema or enanthema, alopecia, anaphylactic or anaphylactoid reactions (with ACE inhibition increases the number of anaphylactic or anaphylactoid reactions on poisons of insects), increasing the concentration of antinuclear antibodies.

From the hematopoiesis:

infrequently - eosinophilia;

rarely - leukopenia, including neutropenia infrequently - pancreatitis, including fatal outcome, increased activity of pancreatic enzymes in the blood plasma, intestinal angioedema, abdominal pain, gastritis, constipation, dryness of the oral mucosa, increased activity of the "hepatic" transaminase (alanine aminotransferase (ALT), aspartate aminotransferase (ACT)) and the concentration of conjugated bilirubin in blood plasma, anorexia, decreased appetite; rarely - glossitis, cholestatic jaundice, hepatocellular lesions; frequency unknown - aphthous stomatitis, acute hepatic insufficiency, cholestatic or cytolytic hepatitis (lethal outcome was extremely rare). From the respiratory system: often - a dry cough (worse at night in the "lying" position), sinusitis, bronchitis, dyspnea;

infrequently - bronchospasm, including weighting of the course of bronchial asthma, congestion of the nose.

From the skin: often - skin rash, in particular maculopapular;

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

rarely - exfoliative dermatitis, urticaria, onycholysis;

very rarely photosensitization reactions; frequency is unknown - toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, psoriasis, psoriasis-like dermatitis, pemphigoid or lichenoidal exanthema or enanthema, alopecia, anaphylactic or anaphylactoid reactions (with ACE inhibition, the number of anaphylactic or anaphylactoid reactions increases on Poisons of Hymenoptera Insects), an increase in the titer of antinuclear antibodies.

From the hematopoiesis: infrequently - eosinophilia;

rarely - leukopenia, including neutropenia and agranulocytosis, a decrease in the number of erythrocytes in the peripheral blood, a decrease in the concentration of hemoglobin, thrombocytopenia;

frequency unknown - oppression of bone marrow hematopoiesis, pancytopenia, hemolytic anemia.

Other:

infrequently - hyperthermia.

Laboratory indicators:

often - an increase in the content of potassium in blood;

an unknown frequency - a decrease in the sodium content in the blood. Cases of development have been reported hypoglycemia in patients with diabetes who took insulin and oral hypoglycemic drugs.

Overdose:

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

Treatment: in mild cases of overdose - gastric lavage, intake of absorbents and sodium sulfate (preferably within 30 minutes after administration).

With a marked decrease in blood pressure - replenishment of the volume of circulating blood, restoration of indicators of water-electrolyte balance of blood, intravenous injection of catecholamines, angiotensin II; at a bradycardia - statement of the artificial driver of a rhythm. In case of overdose, it is necessary to control serum concentrations of creatinine and electrolytes. Hemodialysis is ineffective.

Interaction:

Contraindicated combinations The use of some high-permeability membranes with a negatively charged surface (for example, polyacrylonitrile membranes) during hemodialysis or hemofiltration and the use of dextran sulfate atThe apheresis of low-density lipoproteins increases the risk of developing severe anaphylactic reactions.

Not recommended combinations With potassium salts, potassium-sparing diuretics (for example, amiloride, tri-terene, spironolactone), a more pronounced increase in potassium in the blood serum is possible (with simultaneous use, regular monitoring of potassium content in the blood serum is required). Combinations that should be used with caution

With antihypertensive agents (especially diuretics) and other drugs that lower blood pressure (nitrates, tricyclic antidepressants), potentiation of antihypertensive effect is noted; when combined with diuretics should monitor the sodium content in the blood serum.

With a preparation of gold (sodium aurotomy malate) for intravenous administration, rarely hyperemia of the face, nausea, vomiting, hypotension.

With hypnotics, narcotic analgesics, means for general anesthesia and anesthetics, it is possible to increase antihypertensive action.

With vasopressor sympathomimetics (epinephrine), a decrease in the antihypertensive effect of ramipril is observed, regular monitoring of blood pressure is required.

With allopurinol, procainamide, cytostatics, immunosuppressants, systemic glucocorticosteroids and other agents that can affect hematologic indices, the risk of developing leukopenia increases.

Lithium salts show an increase in serum lithium concentration and an increase in the cardio- and neurotoxic effect of lithium. With hypoglycemic agents for oral administration (derivatives of sulfonyl urea, biguanides), insulin due to 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 in a daily dose of more than 3 g) may weaken the action of ramipril, increase the risk of renal dysfunction and increase the potassium content in the blood serum.

With heparin, an increase in the serum potassium content is possible.

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

With ethanol, there is an increase in the symptoms of vasodilation. Ramipril can enhance the adverse effects of ethanol on the body.

With estrogens, weakened anti-hypertensive effects of ramipril (fluid retention)

Desensitizing therapy with increased sensitivity to insect venoms: ACE inhibitors, including ramipril,increase the likelihood of developing severe anaphylactic or anaphylactoid reactions to poisons of Hymenoptera insects.

Against the background of treatment with ACE inhibitors, hypersensitivity reactions to the venom of Hymenoptera insects (for example, bees, wasps) develop more rapidly and take more severe course. If desensitization to the venom of Hymenoptera is necessary, the ACE inhibitor must be temporarily replaced with a corresponding drug of another class.

Special instructions:

Treatment with the drug Dilaprel® is usually long, its duration in each case is determined by the doctor. It also requires regular medical supervision, in particular in patients with impaired liver function and kidney function.

Before starting treatment with the drug Dilaprel®, 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 starting Dilaprel® (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 ones), it is necessary to ensure careful medical observation of the patient for at least 8 hours to promptly take appropriate measures in case of excessive blood pressure lowering.

If the drug Dilaprel is used for the first time or in a high dose in patients with increased activity of RAAS, they should carefully monitor blood pressure, especially at the beginning of treatment, since these patients there is 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 myocardium, treatment with the drug Dilaprel ® should be started only in a hospital.

In patients with chronic heart failure, taking the drug may lead to a marked decrease in blood pressure, which in some cases is accompanied by oliguria or azotemia and rarely - the development of acute renal failure. Caution should be exercised in the treatment of elderly patients, since they may be particularly sensitive to ACE inhibitors; in the initial phase of treatment it is recommended to monitor the indicators of kidney function (see also the section "Method of administration and dose").

In patients for whom a decrease in blood pressure may pose a certain risk (for example, in patients with atherosclerotic narrowing of the coronary or cerebral arteries), treatment should begin under strict medical supervision. Care should be taken with physical activity and / or hot weather 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 Dilaprel ® 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 development 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 (lip, eyelid) or tongue, impaired swallowing or breathing, the patient should immediately stop taking the drug. Angioedema, localizingin 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 with 0.1 mg of epinephrine (under the control of blood pressure, heart rate and ECG) with the subsequent application of glucocorticosteroids (iv, in / m or inside); It is also recommended intravenous administration of antihistamines (blockers Hi- and Hg-histamine receptors), and in case of inactivation of the enzyme Inactivators C i-esterase can consider the need to introduce in addition to adrenaline (epinephrine) inhibitors of the enzyme C1-esterase.The patient should be hospitalized, and follow-up should be performed until 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. Intestinal angioedema was diagnosed with computer tomography, ultrasound, or surgery. When a patient appears on the background of treatment with ACE inhibitors of the symptoms described above, the differential diagnosis should also consider the possibility of developing an intestinal angioedema.

Treatment aimed at desensitization to poison Hymenoptera (bees, wasps), and simultaneous reception of ACE inhibitors can trigger anaphylactic and anaphylactoid reactions (e.g., reduced blood pressure, dizziness, vomiting, allergic skin reactions), which may sometimes be life threatening.Against the background of treatment with ACE inhibitors, hypersensitivity reactions to the venom of Hymenoptera insects (for example, bees, wasps) develop more rapidly and take more severe course. If a desensitization to the venom of Hymenoptera insects, the ACE inhibitor must be temporarily replaced by an appropriate drug of another class. With the use of ACE inhibitors, life-threatening, rapidly developing anaphylactoid reactions have been described, sometimes up to the development of shock during hemodialysis or plasma filtration using certain high-flow membranes (for example, polyacryliclnitrile membranes) (see also the instructions of membrane manufacturers). It is necessary to avoid the joint use of Dilaprel ® 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.

Before surgery (including dentistry), an anesthesiologist should be warned about the use of ACE inhibitors.

Before and during therapy with ACE inhibitors, a total number of leukocytes and a leukocyte formula must be determined.

The safety and efficacy of Dilaprel® in children and adolescents under 18 years of age has not been established.

In patients with impaired hepatic function, the response to Dilaprel® treatment may be either exacerbated or weakened. In addition, in patients with cirrhosis of the liver with edema and / or ascites, a significant activation of the renin-angiotensin-aldosterone system (RAAS) is possible, therefore, care should be taken with these patients.

Control of laboratory parameters before and during treatment with Dilaprel® (up to 1 time per month for the first 3-6 months) is especially important in patients with an increased risk of neutropenia -renal function, systemic connective tissue diseases or in patients receiving high doses of the drug, as well as at the first signs of infection. When neutropenia is confirmed (the number of neutrophils is less than 2000 / μL) therapy with ACE inhibitors should be discontinued.

In the treatment of ACE inhibitors in the first weeks of treatment and in the subsequent it is recommended that control of kidney function. Particularly careful monitoring is required for patients with acute and chronic heart failure, impaired renal function, after kidney transplantation, patients with renovascular disease, including patients with hemodynamically significant unilateral renal artery stenosis in the presence of two kidneys (in such patients, even a slight increase in the serum creatinine concentration may be indicative of a decrease in renal function).

Control of the content of electrolytes: regular monitoring of the potassium content in the blood 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. It is recommended that parameters of a general blood test to identify 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 simultaneously other drugs that can change 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. When symptoms appear due to leukopenia (eg, fever, enlargement of lymph nodes, tonsillitis), urgent monitoring of the peripheral blood pattern is necessary. 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 significant increase in the activity of "liver" enzymes, treatment with Dilaprel® 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 Dilaprel®, caution should be exercised when driving vehicles and practicing other potentially hazardous activities,requiring increased concentration of attention 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 10 mg.

For 7, 10 or 14 capsules in a planar cell packaging made of polyvinylchloride film and aluminum foil. 2 or 4 contour packs of 7 capsules or 1, 2, 3, 5 or 6 contourcell packs of 10 capsules or 1, 2 or 4 contour packs of 14 capsules together with instructions for use in a pack of cardboard.

Packaging:For 7, 10 or 14 capsules in a planar cell packaging made of polyvinylchloride film and aluminum foil. 2 or 4 contour packs of 7 capsules or 1, 2, 3, 5 or 6 contourcell packs of 10 capsules or 1, 2 or 4 contour packs of 14 capsules together with instructions for use in a pack of cardboard.

Storage conditions:

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

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-000892

Date of registration:18.10.2011

The owner of the registration certificate:VERTEKS, AO VERTEKS, AO Russia

Manufacturer: & nbsp

VERTEKS, AO Russia

Information update date: & nbsp18.10.2011

Illustrated instructions

Instructions

Dilasprel® (Dilaprel®)