Дилапрел®

General characteristics. Structure:

Active ingredient: 0,01 g of a ramipril.

Excipients: lactoses monohydrate - 0,1355 g, silicon dioxide colloid - 0,0030 g, calcium stearate - 0,0015 g and gelatinous solid capsules: titanium dioxide - 2%, gelatin - to 100%.

Antihypertensive cardiodrug.

Pharmacological properties:

Pharmacodynamics. Ramipril inhibits an angiotensin-converting enzyme (APF), blocks transformation of angiotensin I into angiotensin II therefore (irrespective of activity of a renin of a blood plasma) the anti-hypertensive effect develops (in position of the patient lying and standing) without compensatory increase in the heart rate (HR). Reduces products of Aldosteronum.

Reduces the general peripheric resistance of vessels (GPRV) or an afterload, pressure in pulmonary capillaries (preloading), resistance in pulmonary vessels; increases the minute volume of blood and tolerance to loading. At prolonged use promotes myocardium hypertrophy involution at patients with arterial hypertension. Reduces the frequency of arrhythmias at myocardium reperfusion; improves blood supply of an ischemic myocardium; prevents the changes of an endothelium of vessels caused by a high-cholesteric diet. Strengthens a coronary and renal blood stream. The beginning of anti-hypertensive action - in 1,5 h after intake, the maximum effect - in 5-9 h, action duration - 24 h. There is no withdrawal. At patients with the heart failure which developed in the first days of an acute myocardial infarction (2-9 days) at reception of a ramipril, since 3 till the 10th days of an acute myocardial infarction, the risk of rate of mortality (decreases by 27%), risk of sudden death (for 30%), risk of progressing of chronic heart failure to heavy (the III-IV functional class on NYHA classification) / resistant to therapy (for 27%), probability of the subsequent hospitalization because of development of heart failure (for 26%).
At a diabetic and not diabetic nephropathy reception of a ramipril slows down the speed of progressing of a renal failure and time of approach of an end-stage of a renal failure and, thanks to it, reduces the need for a hemodialysis or transplantation of a kidney. At initial stages of a diabetic or not diabetic nephropathy ramiprit reduces albuminuria degree of manifestation.

Pharmacokinetics. After intake ramiprit quickly it is soaked up from digestive tract   (50-60%). Meal slows down its absorption, but does not influence completeness of absorption.
In a liver it is metabolized with formation of an active metabolite of a ramiprilat (inhibits APF 6 times more actively, than ramiprit) and inactive metabolites - diketopiperazine ether, diketopiperazine acid, and also glucuronides of a ramipril and a ramiprilat. All formed metabolites, except for a ramiprilat, have no pharmacological activity. Communication with proteins of a blood plasma for a ramipril - 73%, a ramiprilat - 56%.

After reception of a ramipril inside ramiprit the maximum plasma concentration and the ramiprilat is reached in 1 and 2-4 hours, respectively.

Bioavailability for a ramipril after intake of 2,5-5 mg - 15-28%; for a ramiprilat - 45%. After daily reception of 5 mg/days stable concentration of a ramiprilat in a blood plasma is reached by 4th day. An elimination half-life (T1/2) for a ramipril - 5,1 h; in a phase of distribution and elimination decrease in concentration of a ramiprilat in blood serum happens from T1/2 3 h, then the transitional phase from T1/2 15 h and a long final phase with very low concentration of a ramiprilat in a blood plasma and T1/2 - follows 4-5 days. T1/2 increases at the chronic renal failure (CRF). The volume of distribution of a ramipril - 90 l, a ramiprilat - 500 l.

In researches on animals it was shown that ramiprit it is allocated in maternal milk. It is removed by kidneys - 60%, through intestines - 40% (it is preferential in the form of metabolites). At a renal failure removal of a ramipril and its metabolites is slowed down in proportion to decrease in the clearance of creatinine (CC); at an abnormal liver function transformation in рамиприлат is slowed down; at heart failure concentration of a ramiprilat increases by 1,5-1,8 times.

At healthy volunteers of advanced age (65-76 years) the pharmacokinetics ramiprit and the ramiprilata significantly does not differ from that at young healthy volunteers.

Indications to use:

- arterial hypertension;
- chronic heart failure (as a part of a combination therapy,  in particular in a combination with diuretics);
- the heart failure which developed during the first several days (from the 2nd to the 9th days) after an acute myocardial infarction;
- a diabetic or not diabetic nephropathy the preclinical and clinically expressed stages, including with the expressed proteinuria, in particular, at a combination to arterial hypertension.

Route of administration and doses:

Capsules need to be swallowed entirely and to wash down with enough (1/2 glasses) water, irrespective of meal (that is, capsules can be accepted both to, and in time or after food). The dose is selected depending on therapeutic effect and portability of drug the patient.

Arterial hypertension. Inside, initial dose of 2,5 mg, once, in the morning. If at administration of drug in this dose within 3 weeks and it is not possible to normalize the ABP any more, then the dose can be increased to 5 mg of drug Dilaprel in days. At insufficient efficiency of a dose of 5 mg in 2-3 weeks it can be still doubled to the maximum recommended daily dose of 10 mg a day. As an alternative to increase in a dose up to 10 mg a day at insufficient anti-hypertensive effect of a daily dose of 5 mg addition to treatment of other anti-hypertensive means, in particular, of diuretics or blockers of "slow" calcium channels is possible.

Chronic heart failure. An initial dose of 1,25 mg/days (use of drug is possible ramiprit in other dosage form: tablets on 2,5 mg from risky). Depending on reaction of the patient to the carried-out therapy the dose can be increased. It is recommended to double it bucketed in 1-2 weeks. And more to accept once or to divide doses from 2,5 mg into 2 receptions. Maximum daily dose of 10 mg.

At the heart failure which developed during the first several days (from the 2nd to the 9th days) after an acute myocardial infarction. The initial dose of 5 mg divided into 2 receptions on 2,5 mg in the morning and in the evening. If the patient does not transfer this initial dose (excessive decrease in the ABP is observed), then it is recommended to give within two days on 1,25 mg 2 times a day (in this case it is possible to use drug ramiprit in other dosage form: tablets on 2,5 mg from risky). Then, depending on reaction of the patient, the dose can be increased. It is recommended that the dose at its increase doubled with an interval of 1-3 days. Later, the general daily dose which was divided into two doses in the beginning can once be given. The maximum recommended dose makes 10 mg.

Now experience of treatment of patients with the heavy chronic heart failure (the III-IV functional class on NYHA classification) which arose directly after an acute myocardial infarction is insufficient. If at such patients the decision on performing treatment by drug Dilaprel is made, it is recommended that treatment began with the smallest possible dose of 1,25 mg of 1 times a day (in this case it is possible to use drug ramiprit in other dosage form: tablets on 2,5 mg from risky), and it is necessary to observe extra care at each increase in a dose.

At a diabetic or not diabetic nephropathy. An initial dose of 1,25 mg (use of drug is possible ramiprit in other dosage form: tablets on 2,5 mg from risky) 1 time a day. The dose can increase to 5 mg once a day. Maximum daily dose of 5 mg.

Drug use Dilaprel at separate groups of patients. Patients with renal failures. At KK from 50 to 20 ml/min. on 1,73 sq.m of a body surface the initial daily dose usually makes 1,25 mg (in this case it is possible to use drug ramiprit in other dosage form: tablets on 2,5 mg from risky). Maximum daily dose of 5 mg.

Patients with incompleteness the corrected loss of liquid and electrolytes, patients with heavy arterial hypertension, and also patients for whom excessive decrease in the ABP represents a certain risk (for example at crushing atherosclerotic damage of coronary and brain arteries).

The initial dose decreases to 1,25 mg/days (in this case it is possible to use drug ramiprit in other dosage form: tablets on 2,5 mg from risky).

Patients with the previous therapy by diuretics. It is necessary at an opportunity to cancel diuretics in 2-3 days (depending on duration of effect of diuretics) before an initiation of treatment drug Dilaprel or , at least, to reduce a dose of the accepted diuretics. Treatment of such patients should be begun with the lowest dose equal to 1,25 mg of a ramipril (in this case it is possible to use drug ramiprit in other dosage form: a pill on 2,5 mg from risky) taken once a day, in the morning. After reception of the first dose and every time after increase in a dose ramiprit and (or) "loopback" diuretics patients have to be under medical observation not less than 8 hours in order to avoid uncontrollable hypotensive reaction.

Patients of advanced age (65 years are more senior). The initial dose decreases to 1,25 mg/days (in this case it is possible to use drug ramiprit in other dosage form: tablets on 2,5 mg from risky).

Patients with abnormal liver functions. Reaction of the ABP to administration of drug Dilaprel can how to amplify (due to delay of removal of a ramiprilat), and to decrease (due to delay of transformation of a low-active ramipril into an active ramiprilat). Therefore in an initiation of treatment careful medical observation is required. Maximum admissible daily dose of 2,5 mg.

Features of use:

Treatment by Dilaprel usually is long, its duration in each case is defined by the doctor. It also demands regular medical control, in particular, from patients with the broken function of a liver and kidneys.

Before an initiation of treatment drug Dilaprel it is necessary to eliminate a hyponatremia and a hypovolemia. At the patients who were earlier accepting diuretics it is necessary to cancel them or, at least, to lower their dose in 2-3 days prior to administration of drug Dilaprel (in this case it is necessary to control carefully a condition of patients with chronic heart failure in connection with a possibility of development of a decompensation at them owing to increase in volume of the circulating blood).

After reception of the first dose of drug, and also at increase in its dose and/or dose of diuretics (especially loopback) it is necessary to provide careful medical observation of the patient within not less than 8 hours for timely acceptance of the appropriate measures in case of excessive decrease in the ABP.

If drug Dilaprel is used for the first time or in a high dose at patients with a superactivity of RAAS, then at them it is necessary to control carefully the ABP, especially in an initiation of treatment as these patients have an increased risk of excessive decrease in the ABP (see the section "With Care").

At malignant arterial hypertension and heart failure, in particular in an acute stage of a myocardial infarction, treatment by drug Dilaprel should be begun only in the conditions of a hospital.

At patients with chronic heart failure administration of drug can lead to development of the expressed decrease in the ABP which in some cases is followed by an oliguria or an azotemia and is rare - development of an acute renal failure.

It is necessary to be careful at treatment of elderly patients as they can be especially sensitive to APF inhibitors, in an initial phase of treatment it is recommended to control indicators of function of kidneys (see also section "Route of Administration and Doses").

At patients for whom decrease in the ABP can represent a certain risk (for example, at patients with atherosclerotic narrowing of coronary or brain arteries) treatment has to begin under strict medical observation.

It is necessary to be careful at an exercise stress and/or hot weather because of risk of the increased sweating and dehydration with development of arterial hypotension owing to reduction of volume of the circulating blood and decrease in concentration of sodium in blood.

During treatment by drug Dilaprel is not recommended to take alcohol.

Passing arterial hypotension is not a contraindication for continuation of treatment after stabilization of the ABP. In case of repeated development of the expressed arterial hypotension it is necessary to reduce a dose or to cancel drug.

At the patients receiving treatment by APF inhibitors cases of a Quincke's disease of the person, extremities, lips, language, a throat or throat were observed. At emergence of puffiness in a face (lips, eyelids) of either language, or disturbance of swallowing or breath the patient has to stop administration of drug immediately.

The Quincke's disease which is localized in the field of language, a throat, or a throat (possible symptoms: disturbance of swallowing or breath) can threaten life and demands carrying out urgent measures for its stopping: hypodermic introduction of 0,3-0,5 mg or intravenous drop administration of 0,1 mg of Epinephrinum (under control of the ABP, ChSS and ECG) with the subsequent use of glucocorticosteroids (in/in, in oil or inside); also intravenous administration of antihistamines is recommended (blockers of H1-and H2 - histamine receptors), and in case of insufficiency of inactivators of C1 esterase enzyme it is possible to consider a question of need of introduction in addition to Epinephrinum of inhibitors of C1 esterase enzyme. The patient has to be hospitalized, and observation of it has to be made before full stopping of symptoms, but not less than 24 hours.

At the patients receiving APF inhibitors cases of an intestinal Quincke's disease which was shown by abdominal pains with nausea and vomiting or without them were observed; in certain cases also the Quincke's disease of the person was at the same time observed. At emergence in the patient against the background of treatment by APF inhibitors of the above described symptoms it is necessary to consider when carrying out the differential diagnosis and the possibility of development in them of an intestinal Quincke's disease. 

(Bees, wasps), and a concomitant use of APF inhibitors anaphylactic and anaphylactoid reactions (for example, decrease in the ABP, short wind, vomiting, allergic skin reactions) which can sometimes be life-threatening can initiate the treatment directed to desensitization to poison of insects. Against the background of treatment by APF inhibitors of hypersensitivity reaction on poison of insects (for example, bees, wasps) develop quicker and proceed heavier. If performing desensitization to poison of insects is necessary, then APF inhibitor has to be temporarily replaced with the corresponding medicine of other class.

At use of APF inhibitors the life-threatening, quickly developing anaphylactoid reactions were described, sometimes up to development of shock during a hemodialysis or a plazmofiltration with use of certain high-flowing membranes (for example, poliakrilnitrilny membranes) (see also instructions of producers of membranes). It is necessary to avoid combined use of drug Dilaprel and such membranes, for example, for an urgent hemodialysis or haemo filtering. In this case use of other membranes or an exception of reception of APF inhibitors is preferable. Similar reactions were observed at an afereza of lipoproteins of low density using a sulfate dextran. Therefore this method should not be applied at the patients receiving APF inhibitors.

Before surgical intervention (including stomatology) it is necessary to warn the anesthesiologist about use of APF inhibitors.

Before the beginning and during therapy by APF inhibitors calculation of total number of leukocytes and definition of a leukocytic formula is necessary.

Safety and efficiency of use of Dilaprel for children and teenagers up to 18 years is not established.

It is recommended to conduct careful observation of newborns who were exposed to pre-natal influence of APF inhibitors, for detection of arterial hypotension, an oliguria and a hyperpotassemia. At an oliguria maintenance of the ABP and renal perfusion by administration of the corresponding liquids and vasoconstrictors is necessary. Newborns have a risk of an oliguria and neurologic frustration, perhaps, because of decrease in a renal and brain blood-groove owing to decrease in the ABP called by APF inhibitors (received by pregnant women and after the delivery).

At patients with chronic heart failure Dilaprel can lead administration of drug to development of the expressed lowering of arterial pressure which in some cases is followed by an oliguria or an azotemia and is rare development of an acute renal failure. Patients with malignant arterial hypertension or the accompanying dekompensirovanny HSN have to begin treatment in the conditions of a hospital.

Patients with abnormal liver functions reaction to treatment by drug can have Dilaprel or strengthened or weakened. Besides, at patients with heavy cirrhosis with hypostases and/or ascites considerable activation the system renin-angiotensin-aldosteronovoy (SRAA) therefore at treatment of these patients it is necessary to observe extra care is possible.

Control of laboratory indicators to and during treatment by drug Dilaprel (to 1 time a month in the first 3-6 months) is especially important at patients with the increased risk of a neutropenia at a renal failure, general diseases of connecting fabric or at the patients receiving high doses of drug and also at the first signs of development of an infection. At confirmation of a neutropenia (the number of neutrophils is less than 2 thousand / мкл) therapy by APF inhibitors should be stopped.

At treatment APF inhibitors and in the subsequent recommend to carry out control of function of kidneys to the first weeks of treatment. Especially careful control is required to patients with acute and chronic heart failure, a renal failure, after transplantation of kidneys, to patients with renovascular diseases, including patients with hemodynamically significant unilateral renal artery stenosis in the presence of two kidneys (at such patients even slight increase of concentration of serumal creatinine can be an indicator of depression of function of kidneys).

Control of concentration of electrolytes: regular control of content of potassium in blood serum is recommended. Especially careful monitoring of content of potassium in blood serum is required to patients with renal failures, significant disturbances of water and electrolytic balance, chronic heart failure.

It is recommended to control indicators of the general blood test for identification of a possible leukopenia. More regular control is recommended in an initiation of treatment and at patients with a renal failure, and also at patients with diseases of connecting fabric or at the patients receiving at the same time other medicines capable to change a picture of peripheral blood (see the section "Interaction with Other Medicines"). Control of quantity of leukocytes is necessary for early identification of a leukopenia that is especially important at patients with the increased risk of its development, and also at the first signs of development of an infection. At emergence of the symptomatology caused by a leukopenia (for example, fevers, a hyperadenosis, tonsillitis), urgent control of a picture of peripheral blood is necessary. In case of signs of bleeding (the smallest petechias, a red-brown enanthesis and mucous membranes) also control of number of thrombocytes in peripheral blood is necessary.

At emergence of jaundice or significant increase in activity of "hepatic" enzymes treatment by drug Dilaprel should be stopped and provided medical observation of the patient.  

Influence on control of vehicles and mechanisms. During treatment by drug Dilaprel it is necessary to be careful during the driving of motor transport and occupations other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions (dizziness, especially after an initial dose of APF inhibitor at the patients accepting diuretic medicines is possible).

Use at pregnancy and during breastfeeding. Dilaprel it is not necessary to apply at pregnancy. Therefore before an initiation of treatment it is necessary to be convinced of lack of pregnancy. If the patient became pregnant during treatment, it is necessary to replace medicinal therapy by Dilaprel with other therapy as soon as possible. Otherwise there is a risk of disturbance of development of kidneys of a fruit, a lowering of arterial pressure of a fruit and newborns, renal failures, hyperpotassemias, hypoplasias of bones of a skull, an oligogidramnion, a contracture of extremities, deformations of a skull, a hypoplasia of lungs, especially in the I trimester of pregnancy. If treatment by Dilaprel is necessary in the period of a lactation, then breastfeeding should be stopped.

Side effects:

The listed below undesirable effects are given according to the following gradation of frequency of their emergence:
very often: (10%);
often:  (≥1% - <10%);
infrequently: (≥0,1% - 1%);
seldom:  (≥0,01% - 0,1%);
very seldom: (0,01%, including separate messages);
frequency is unknown: according to the available data it is not possible to establish emergence frequency.

From cardiovascular system: often excessive decrease in the ABP, orthostatic hypotension, syncopal states, stethalgias; infrequently myocardium ischemia, including development of an attack of stenocardia or myocardial infarction, tachycardia, arrhythmias (emergence or strengthening), a heart consciousness, peripheral hypostases, "inflows" of blood to face skin.

From urinogenital system: infrequently a renal failure, including development of an acute renal failure, increase in amount of the emitted urine, strengthening of the existing proteinuria, increase in concentration of urea and creatinine in blood, passing impotence at the expense of erectile dysfunction, decrease in a libido; frequency is unknown a gynecomastia.

From the central nervous system: often a headache, feeling of "ease" in the head, feeling of fatigue; infrequently dizziness, an ageusia (loss of flavoring sensitivity), a dysgeusia (disturbance of flavoring sensitivity), the suppressed mood, uneasiness, hypererethism, motive concern, sleep disorders, including drowsiness; seldom a tremor, development or strengthening of disturbances of blood circulation against the background of the stenosing vascular defeats, a vasculitis, an adynamy, balance disturbance, confusion of consciousness; frequency is unknown Reynaud's syndrome, brain ischemia, including an ischemic stroke and passing disturbance of cerebral circulation, disturbance of psychomotor reactions, paresthesias (burning sensation), parosmiya (disturbance of perception of smells), disturbance of attention, a depression.

From sense bodys: infrequently visual disturbances, including a sight vagueness; seldom conjunctivitis, hearing disorder, sonitus.

From a musculoskeletal system: often muscular spasms, mialgiya; infrequently arthralgia.

From the alimentary system: often inflammatory reactions in a stomach and intestines, digestion disturbance, a sensation of discomfort in a stomach, dyspepsia, diarrhea, nausea, vomiting; infrequently pancreatitis, including with a lethal outcome, increase in activity of enzymes of a pancreas in a blood plasma, an intestinal Quincke's disease, an abdominal pain, gastritis, a lock, dryness of a mucous membrane of an oral cavity, increase in activity of liver enzymes and concentration of the conjugated bilirubin in a blood plasma, anorexia, a loss of appetite; seldom glossitis, cholestatic jaundice, hepatocellular defeats; frequency is unknown aphthous stomatitis, an acute liver failure, cholestatic or cytolytic hepatitis (the lethal outcome was observed extremely seldom).

From respiratory system: often dry cough (amplifying at night in a prone position), sinusitis, bronchitis, short wind; infrequently a bronchospasm, including weighting of a course of bronchial asthma, a nose congestion.

From integuments: often skin rash, in particular makulezno-papular; infrequently Quincke's disease, including with a lethal outcome (hypostasis of a throat can cause the obstruction of respiratory tracts leading to a lethal outcome), a skin itch, a hyperhidrosis (the increased perspiration); seldom exfoliative dermatitis, small tortoiseshell, онихолизис; very seldom reactions of a photosensitization; frequency is unknown a toxic epidermal necrolysis, Stephens-Johnson's syndrome, a multiformny erythema, a pempigus, weighting of a course of psoriasis, psoriazopodobny dermatitis, a pemfigoidny or lichenoid (lishayevidny) dieback or an enantema, an alopecia, anaphylactic or anaphylactoid reactions (at inhibition of APF the number of anaphylactic or anaphylactoid reactions to poisons of insects increases), increase in concentration of antinuclear antibodies.

From bodies of a hemopoiesis: infrequently eosinophilia; seldom a leukopenia, including a neutropenia and an agranulocytosis, reduction of quantity of erythrocytes in peripheral blood, decrease in concentration of hemoglobin, thrombocytopenia; frequency is unknown oppression of a marrowy hemopoiesis, a pancytopenia, hemolitic anemia.

Others: infrequently hyperthermia.

Laboratory indicators: increase in content of potassium in blood is frequent; unknown frequency decrease in content of sodium in blood. It was reported about cases of development of a hypoglycemia in patients with a diabetes mellitus which accepted insulin and peroral hypoglycemic medicines.

Interaction with other medicines:

Contraindicated combinations. Use of some high-flowing membranes with a negatively charged surface (for example, poliakrilnitrilny membranes) when carrying out a hemodialysis or haemo filtering and using a dextran of sulfate at an afereza of lipoproteins of low density increases risk of development of heavy anaphylactic reactions.

Not recommended combinations. With potassium salts, kaliysberegayushchy diuretics (for example, amiloride, Triamterenum, Spironolactonum) perhaps more expressed increase in content of potassium in blood serum (at simultaneous use regular control of content of potassium in blood serum is required).

Combinations which should be applied with care. With anti-hypertensive means (especially diuretics) and other drugs, the reducing ABP (nitrates, tricyclic antidepressants) note potentiation of anti-hypertensive effect; at a combination with diuretics it is necessary to control the content of sodium in blood serum.

With injection drugs of gold the hyperemia of the person, nausea, vomiting, hypotension are seldom possible.

With somnolent, narcotic analgetics, means for the general anesthesia and anesthetics strengthening of anti-hypertensive action is possible.

With angiotonic sympathomimetics (Epinephrinum) reduction of anti-hypertensive action of a ramipril is noted, regular control of the ABP is required.

With Allopyrinolum, procaineamide, cytostatics, immunodepressants, system glucocorticosteroids and other means which can influence hematologic indicators the risk of development of a leukopenia increases.

With salts of lithium increase in serumal concentration of lithium and strengthening kardio-and neurotoxic effect of lithium is noted.

With hypoglycemic means for intake (sulphonylurea derivatives, guanyl guanidines), insulin in connection with reduction of insulin resistance under the influence of a ramipril strengthening of hypoglycemic effect of these drugs is possible, up to development of a hypoglycemia.

Combinations which should be taken into account. With non-steroidal anti-inflammatory drugs (indometacin, acetylsalicylic acid) weakening of action of a ramipril, increase in risk of a renal failure and increase in content of potassium in blood serum is possible.

With heparin increase in content of potassium in blood serum is possible.

From sodium chloride weakening of anti-hypertensive action of a ramipril and less effective treatment of symptoms of chronic heart failure is possible.

With ethanol strengthening of symptoms of a vazodilatation is noted. Ramipril can strengthen an adverse effect of ethanol on an organism.

With estrogen weakening of anti-hypertensive action of a ramipril (a liquid delay) is noted.

The desensibilizing therapy at hypersensitivity to poisons of insects: APF inhibitors, including ramiprit, increase probability of development of heavy anaphylactic or anaphylactoid reactions to poisons of insects.

Against the background of treatment by APF inhibitors of hypersensitivity reaction on poison of insects (for example, bees, wasps) develop quicker and proceed heavier. If performing desensitization to poison of insects is necessary, then APF inhibitor has to be temporarily replaced with the corresponding medicine of other class.

Contraindications:

- hypersensitivity to a ramipril, other APF inhibitors or to any of drug components (see the section "Structure");
- a Quincke's disease (hereditary or idiopathic, and also after reception of APF inhibitors), in the anamnesis risk of bystry development of a Quincke's disease;
- hemodynamically significant stenosis of renal arteries (bilateral or unilateral in case of the only kidney);
- hemodynamically significant stenosis of the aortal or mitral valve or hypertrophic subaortic stenosis (GOKMP);
- the expressed renal failure (the clearance of creatinine (CC) less than 20 ml/min. at a body surface of 1,73 sq.m);
- hemodialysis;
- primary hyper aldosteronism;
- pregnancy, lactation period;
- age up to 18 years (safety and efficiency of use are not studied);
- the hyposensibilizing therapy at hypersensitivity reactions to poisons of insects, such as bees, wasps;
- arterial hypotension (the systolic arterial pressure (AP) is less than 90 mm hg) or states with unstable indicators of a hemodynamics;
- аферез lipoproteins of low density with use of a dextran of sulfate (danger of development of reactions of the raised chuvtvitelnost);
- a nephropathy which treatment is carried out by glucocorticosteroids, non-steroidal anti-inflammatory drugs, immunomodulators and/or other cytotoxic means (see the section "Interaction with Other Medicines");
- chronic heart failure in a decompensation stage (experience of a clinical use is insufficient);
- lactose intolerance; deficit of lactase; glyukozo-galaktozny malabsorption.

Additional contraindications at drug use Dilaprel in an acute stage of a myocardial infarction:
- heavy chronic heart failure (the III-IV functional class on NYHA classification);
- unstable stenocardia;
- life-threatening ventricular disturbances of a heart rhythm;
- "pulmonary" heart.

With care:
- states at which the excessive lowering of arterial pressure is especially dangerous (at atherosclerotic damages of coronary and brain arteries);
- the states which are followed by increase in activity of the renin-angiotenzin-aldosteronovy system (RAAS) at which at inhibition of APF there is a risk of sharp decrease in the ABP with deterioration in function of kidneys:
• the expressed arterial hypertension, especially malignant arterial hypertension;
• chronic heart failure, especially heavy or concerning which other medicines with anti-hypertensive action are accepted;
• hemodynamically significant unilateral renal artery stenosis (in the presence of both kidneys);
• the previous reception of diuretics;
• disturbances of water and electrolytic balance as a result of insufficient consumption of liquid and table salt, diarrhea, vomiting, plentiful sweating;
- general diseases of connecting fabric, including a system lupus erythematosus, a system scleroderma, the accompanying therapy by the miyelotoksichny drugs capable to cause changes in a picture of peripheral blood (oppression of a marrowy blood formation, development of a neutropenia or agranulocytosis is possible);
- renal failures (KK more than 20 ml/min. at a body surface of 1,73 sq.m) because of risk of development of a hyperpotassemia and a leukopenia;
- advanced age (risk of strengthening of anti-hypertensive action);
- abnormal liver functions (insufficiency of experience of use: perhaps both strengthening, and easing of effects of a ramipril; in the presence at patients of cirrhosis with ascites and hypostases considerable activation of RAAS, see above "the state which are followed by increase in activity of RAAS" is possible);
- diabetes mellitus (risk of development of a hyperpotassemia);
- a state after transplantation of kidneys;
- hyperpotassemia.

Overdose:

Symptoms: an excessive vazodilatation with development of the expressed lowering of arterial pressure, shock; bradycardia, disturbance of water and electrolytic balance, acute renal failure, stupor.

Treatment: in mild cases of overdose a gastric lavage, reception of absorbents and sodium of sulfate (it is desirable within 30 min. after reception).

At the expressed lowering of arterial pressure completion of volume of the circulating blood, recovery of indicators of water and electrolytic balance of blood, intravenous administration of catecholamines, angiotensin II; at bradycardia statement of an artificial pacemaker. At overdose it is necessary to control serumal concentration of creatinine and electrolytes. The hemodialysis is inefficient.

Storage conditions:

In the dry, protected from light place at a temperature not over 25 ºС. To store in the place, unavailable to children. Period of validity 2 years. Not to use after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Capsules of 10 mg. On 7, 10 or 14 capsules in a blister strip packaging from a film of polyvinyl chloride and aluminum foil. 2 or 4 blister strip packagings on 7 capsules or 1, 2, 3, 5 or 6 blister strip packagings on 10 capsules or 1, 2 or 4 blister strip packagings on 14 capsules together with the application instruction in a pack from a cardboard.