Pharmacological properties

Pharmacodynamics. ramiprilat, the active metabolite of a ramipril, suppresses enzyme to a dipeptidilkarboksipeptidaz і (synonyms: apf, kininaza of ii). in blood plasma and fabrics this enzyme catalyzes angiotensin transformation і in active vasopressor substance angiotensin іі and also disintegration of an active vazodilatator of bradykinin. reduction of amount of angiotensin іі and oppression of disintegration of bradykinin is conducted to a vazodilatation.

As angiotensin ІІ also stimulates with

release of Aldosteronum, ramiprilat promotes decrease in secretion of Aldosteronum. Reaction to monotherapy by APF inhibitors on average was the negroid race (Afro-Caribbean origin) which was less expressed at patients with AG (population of which the low level of renin at AG is characteristic), than at representatives of other races.

Purpose of a ramipril causes significant decrease in peripheric resistance of arteries. Generally, medicament essentially does not change a renal blood stream and glomerular filtration rate.

Purpose of a ramipril to patients with AG leads

to decrease in the ABP level in prone positions and standing without compensatory increase in ChSS.

antihypertensive effect is shown by

At most of patients in 1–2 h after medicament use, reaches a maximum in 3–6 h and lasts for 24 h. The maximum therapeutic effect is usually reached after constant use in 3–4 weeks. It is established that the antihypertensive effect remains at long therapy for 2 years. Sudden phase-out of a ramipril does not cause fast and sharp increase in the ABP.

diuretics and, as necessary, cardiac glycosides ramiprit

In addition to usual therapy it is effective at patients with the II-IV functional class (FC) on NYHA. Drug shows favorable effects on a warm hemodynamics (pressure decrease of filling of the left and right ventricles, OPSS, increase in warm emission and improvement of cardiac index). It also reduces neuroendocrinal activation.

Pharmacokinetics. Absorption. After oral administration ramiprit quickly it is absorbed in a GIT: it With _max in blood plasma is reached during 1 h. Extent of absorption is 56%, this rate does not depend on existence of food in a GIT. With _max ramiprilat, the only active metabolite of a ramipril, it is reached in blood plasma in 2–4 h after administration of drug. In case of use of a usual dose (1 times a day) equilibrium concentration of the ramiprilat in blood plasma is reached for the 4th day of treatment.

Distribution. Linking of a ramipril with proteins of blood plasma makes about 73%, and the ramiprilat — 56%.

Metabolism. Ramipril is almost completely metabolized to the ramiprilat, diketopiperazine ether, diketopiperazine acid and glucuronides of a ramipril and the ramiprilat.

Removal. Excretion of metabolites mainly renal. Decrease in concentration of the ramiprilat in blood plasma happens in several phases. Considering powerful saturated linking with APF and slow dissociation with enzyme, ramiprilat it is characterized the elimination prolonged by a terminal phase at very low concentration in blood plasma.

After multiple dose of a ramipril of its T _½ made 13–17 h for doses of 5-10 mg and 1.25-2.5 mg are a little longer for doses. Such distinction is caused by the saturating ability of enzyme concerning binding of the ramiprilat.

ramiprit

At reception of a single dose and its metabolite was not revealed in breast milk. However the effect of repeated doses is unknown.

Renal excretion of the ramiprilat is reduced by

at patients with impaired renal function. At patients with damage of a liver the metabolism of a ramipril is slowed down that is caused by reduced activity of hepatic esterases, the level of a ramipril in blood plasma of these patients was increased. However With _max ramiprilat at such patients did not differ from that at patients with normal function of a liver.

Indication

Lecheniye ag. prevention of cardiovascular diseases: decrease in cardiovascular incidence and mortality at patients with:

• profound cardiovascular diseases of aterotrombotichesky genesis (existence in the anamnesis of an ischemic heart disease or stroke, or diseases of peripheral vessels);
• diabetes which have at least one factor of cardiovascular risk (see. Pharmacological PROPERTIES).

Lecheniye of a disease of kidneys:

• an initial glomerular diabetic nephropathy to which presence of a microalbuminuria testifies;
• expressed glomerular diabetic nephropathy to which presence of a macroproteinuria, at the patients having at least one factor of cardiovascular risk (testifies see. Pharmacological PROPERTIES);
• expressed glomerular not diabetic nephropathy to which presence of a macroproteinuria of ≥3 g/days (testifies see. Pharmacological PROPERTIES).

Lecheniye of the heart failure which is followed by clinical manifestations. Secondary prevention after the postponed acute myocardial infarction: decline in mortality during the acute stage of a myocardial infarction at patients with clinical signs of heart failure at an initiation of treatment more than in 48 h after developing of an acute myocardial infarction.

Use

Drug for oral administration.

Rami Sandoz is recommended to accept

daily at the same time. The medicament can be taken to, in time and after a meal as meal does not affect bioavailability of drug. Rami Sandoz it is necessary to swallow of tablets entirely, washing down with water. They cannot be chewed or crushed.

Adult. Rami Sandoz can cause arterial hypotension which development is more probable at the patients who are at the same time receiving diuretics. In similar cases it is recommended to show care as at these patients the decrease in OCK and/or electrolytes is possible. It is desirable to stop use of diuretic in 2–3 days prior to medicament treatment Rami Sandoz if it is possible (see. Special INSTRUCTIONS).

medicament use Rami Sandoz should begin with

At patients with AG which cannot cancel diuretic with a dose 1.25 mg. It is necessary to control carefully function of kidneys and level of potassium in blood. The further dose Rami Sandoz should be adjusted depending on the AD target level.

AG. The dose should be selected individually, depending on a condition of the patient (see. Special INSTRUCTIONS) and results of control measurements of the ABP. Rami Sandoz it is possible to apply as monotherapy or in a combination with antihypertensive medicines of other classes.

Initial dose. Drug treatment Rami Sandoz should be begun gradually, starting with recommended an initial dose of 2.5 mg/days

At patients with considerable activation system renin-angiotensin-aldosteronovoy after reception of an initial dose can arise considerable decrease in the ABP. For such patients the recommended dose makes 1.25 mg, and their treatment should be begun under control (see. Special INSTRUCTIONS).

Titration of a dose and maintenance dose. A dose it is possible to double each 2–4 weeks before achievement of the AD target level; the maximum dose Rami Sandoz makes 10 mg/days. As a rule, the medicament is taken 1 time a day.

Prevention of cardiovascular diseases. Initial dose. The recommended initial dose of medicament Rami Sandoz makes 2.5 mg of 1 times a day.

Titration of a dose and maintenance dose. Depending on individual tolerance of medicament the dose should be raised gradually. It is recommended to double a dose in 1–2 weeks of treatment, and then in 2–3 weeks to raise it to a target maintenance dose of 10 mg of 1 times a day. Also see. information given above concerning medicament dosing for the patients receiving diuretics.

Treatment of a disease of kidneys. At patients with diabetes and a microalbuminuria. Initial dose. The recommended initial dose of medicament Rami Sandoz makes 1.25 mg of 1 times a day.

Titration of a dose and maintenance dose. Depending on individual tolerance of medicament at further treatment the dose is raised. In 2 weeks of treatment about 2.5 mg, and then up to 5 mg in 2 weeks of treatment are recommended to double a single dose.

At patients with diabetes and not less than one factor of cardiovascular risk

Initial dose. The recommended initial dose of medicament Rami Sandoz makes 2.5 mg of 1 times a day.

Titration of a dose and maintenance dose. Depending on individual tolerance of medicament at further treatment the dose is raised. In 1–2 weeks of treatment Rami Sandoz is recommended to double a medicament dose to 5 mg, and then up to 10 mg in 2–3 weeks of treatment. The target daily dose makes 10 mg.

At patients and not diabetic nephropathy to which presence of a macroproteinuria of ≥3 g/days testifies. Initial dose. The recommended initial dose of medicament Rami Sandoz makes 1.25 mg of 1 times a day.

Titration of a dose and maintenance dose. Depending on individual shipping the patient of medicament at further treatment the dose is raised. In 2 weeks of treatment about 2.5 mg, and then up to 5 mg in 2 weeks of treatment are recommended to double a single dose.

Heart failure with clinical manifestations. Initial dose. For patients whose condition was stabilized after treatment by diuretics the recommended initial dose makes 1.25 mg/days

Titration of a dose and a maintenance dose. A medicament dose Rami Sandoz each 1–2 weeks before achievement of the maximum daily dose titrate by its doubling 10 mg. It is desirable to distribute a dose on 2 receptions.

Secondary prevention after the postponed acute myocardial infarction in the presence of heart failure. Initial dose. In 48 h after developing of a myocardial infarction to patients whose condition clinically and hemodynamically steadily, 2 times a day within 3 days appoint an initial dose of 2.5 mg. If the initial dose of 2.5 mg is transferred badly, then it is necessary to apply a dose of 1.25 mg 2 times a day within 2 days with the subsequent increase to 2.5 and 5 mg 2 times a day. If it is impossible to raise a dose to 2.5 mg 2 times a day, treatment should be cancelled. See information given above concerning medicament dosing for the patients receiving diuretics.

Titration of a dose and maintenance dose. Further a daily dose 2 times a day increase by its doubling at an interval of 1–3 days to achievement of a target maintenance dose 5 mg. When it is possible, the maintenance dose is divided into 2 receptions.

If cannot raise a dose to 2.5 mg 2 times a day, treatment should be cancelled. With heavy (the IV FC on classification of NYHA) heart failure right after a myocardial infarction has still not enough experience of treatment of patients. If the decision on treatment of such patients is made by this drug, it is recommended to begin therapy with a dose of 1.25 mg of 1 times a day and any its increase to carry out with extreme care.

Special categories of patients

Patients with a renal failure. The daily dose for patients with a renal failure depends on an indicator of clearance of creatinine (see. PHARMACOLOGICAL PROPERTIES):

if the clearance of creatinine of ≥60 ml/min., need for correction of an initial dose (2.5 mg/days) is not present

• , and the maximum daily dose makes 10 mg;
if the clearance of creatinine of 30-60 ml/min., need for correction of an initial dose (2.5 mg/days) is not present
• , and the maximum daily dose makes 5 mg;
• if the clearance of creatinine of 10-30 ml/min., an initial dose is 1.25 mg/days, and the maximum daily dose — 5 mg;
• patients about AG which are on a hemodialysis: at a hemodialysis ramiprit it is removed slightly; the initial dose makes 1.25 mg, and the maximum daily dose — 5 mg; the medicament should be taken in several hours after holding a session of a hemodialysis.

Patients with an abnormal liver function (see. Pharmacological PROPERTIES). Drug treatment Rami Sandoz at patients with abnormal liver functions should be begun under careful control, and the maximum daily dose in such cases has to make 2.5 mg.

Patients of advanced age. The initial dose has to be lower, and further titration of a dose should be carried out more gradually, considering a high probability of emergence of side effects, especially at patients of strachesky age and persons with an asthenia. In such cases appoint the minimum initial dose — 1.25 mg of a ramipril.

Contraindication

Hypersensitivity to active agent, any other component of medicament or other inhibitors apf; a Quincke's disease in the anamnesis (hereditary, idiopathic or connected with use of inhibitors apf); renal artery stenosis (bilateral or stenosis of an artery of one kidney); heavy renal failure; primary hyper aldosteronism. Rami Sandoz is not applied at patients with arterial hypotension or hemodynamically unstable states.

pregnancy Period (see Use during pregnancy and feeding by a breast).

should not be applied together with the medicaments containing aliskiren at patients with diabetes or a moderate or heavy renal failure (glomerular filtration rate of 60 ml/min.).

needs to avoid simultaneous use of APF inhibitors and extracorporal methods of treatment which lead to contact of blood with negatively charged surfaces as such use can cause anaphylactic reactions of heavy degree. Such extracorporal methods of treatment include dialysis or haemo filtration with use of certain membranes with high hydraulic permeability (for example polyacrylonitrile) and aferez LDL using a sulfate dextran.

Side effects

Side reactions are classified by

by emergence frequency: very often (≥1/10), it is frequent (≥1/100, 1/10), infrequently (≥1/1000, 1/100), is rare (≥1/10,000, 1/1000), is very rare (1/10,000), unspecified (it is impossible to establish on the available data).

from the immune system: unspecified — anaphylactic and anaphylactoid reactions, increase in level of anti-nuclear antibodies.

from a cardiovascular system: often — arterial hypotension, orthostatic decrease in the ABP, a syncope; infrequently — myocardium ischemia, including stenocardia or a myocardial infarction, tachycardia, arrhythmia, heart consciousness, peripheral hypostases, reddening, feeling of inflows; seldom — a stenosis of vessels, hypoperfusion, a vasculitis; very seldom — a short-term ischemic attack, an ischemic stroke; unspecified — Reynaud's syndrome.

from the system of a hemopoiesis: infrequently — an eosinophilia; seldom — reduction of quantity of white cells (including a neutropenia and an agranulocytosis), reduction of quantity of red cells, decrease in level of hemoglobin, reduction of quantity of thrombocytes; unspecified — insufficiency of marrow, a pancytopenia, hemolytic anemia.

from nervous system: often — a headache, dizziness; infrequently — vertigo, paresthesia, an ageusia, a dysgeusia; seldom — a tremor, balance disturbance; unspecified — cerebral ischemia, including an ischemic stroke and the tranzitorny ischemic attack, disturbance of psychomotor functions, heartburn, a parosmiya.

Mental disorders: infrequently — change of mood, alarm, nervousness, concern, a sleep disorder, including a somnolention; seldom — a condition of confusion of consciousness; unspecified — disturbance of attention.

from an organ of sight: infrequently — a disorder of vision, including illegibility of sight; seldom — conjunctivitis.

from an organ of hearing: seldom — a hearing disorder, a ring in ears.

from a respiratory system: often — unproductive cough, bronchitis, sinusitis; infrequently — a bronchospasm, including aggravation OH, congestion of a nose; seldom — dispnoe.

from digestive system: often — inflammation in an oral cavity and a digestive tract, digestive disturbances, discomfort in a stomach, dyspepsia, diarrhea, nausea, vomiting; infrequently — pancreatitis (in isolated cases it was reported about a lethal outcome at use of APF inhibitors), increase in level of enzymes of a pancreas, a Quincke's disease of a small intestine, pain in an upper part of a stomach, including gastritis, a constipation, dryness in a mouth; seldom — a glossitis, sensation of discomfort in an abdominal cavity, a stomach ache; unspecified — aphthous stomatitis.

Disturbance of perception of a smell and taste (for example metal smack), sometimes total loss of taste.

Metabolic disturbances: often — increase in level of potassium in blood; infrequently — anorexia, a loss of appetite; unspecified — decrease in level of sodium in blood.

Gepatobiliarny disturbances: infrequently — increase in level of hepatic enzymes and/or conjugates of bilirubin; seldom — cholestatic jaundice, damage of hepatic cells; unspecified — an acute liver failure, cholestatic or cytolytic hepatitis (in exceptional cases — with a lethal outcome).

from an urinary system: infrequently — a renal failure, including OPN, increase in amount of urine, deterioration in a background proteinuria, increase in level of urea in blood and creatinine.

from a reproductive system: infrequently — tranzitorny erectile impotence, decrease in a libido; unspecified — a gynecomastia.

from skin: often — rash, in particular makulopapulezny, an itching, urticaria; infrequently — a Quincke's disease, in exceptional cases — disturbance of passability of airways owing to a Quincke's disease that can cause a lethal outcome; hyperhidrosis; seldom — exfoliative dermatitis, an urtikariya, an onycholysis; very seldom — reaction of photosensitivity; unspecified — a bladderwort, a toxic epidermal necrolysis, Stephens's syndrome — Johnson, a multiformny erythema, a pempigus, aggravation of a course of psoriasis, psoriasis dermatitis, a pemfigoidny or lichenoid dieback or an enantema, an alopecia.

from the musculoskeletal system: often — muscular spasms, myalgia; infrequently — an arthralgia.

General disorders: often — thorax pain, an asthenia; infrequently — a pyrexia; seldom — weakness, drowsiness, fatigue.

Endocrine disturbances: unspecified — a syndrome of inadequate secretion of antidiuretic hormone.

Special instructions

Special categories of patients. double blockade system renin-angiotensin-aldosteronovoy by means of the medicines containing aliskiren.

Double blockade system renin-angiotensin-aldosteronovoy by the combined medicament use Rami Sandoz and the aliskirena is not recommended to

as at the same time there is an increased risk of developing arterial hypotension, a hyperpotassemia and changes of function of kidneys. To patients with diabetes or renal failures (glomerular filtration rate of 60 ml/min.) combined use Rami Sandoz and an aliskirena contraindicated (see CONTRAINDICATIONS).

Patients with extra risk of arterial hypotension. Patients with the significant activation system renin-angiotensin-aldosteronovoy. The risk of sudden notable decrease in the ABP with deterioration in function of kidneys owing to oppression of APF increases at patients with the significant activation system renin-angiotensin-aldosteronovoy, especially if APF inhibitor or the accompanying diuretic means are appointed for the first time or at the first increase in a dose.

Significant activation renin-angiotensin-aldosteronovoy of a system at which monitoring of the ABP is required can be expected, for example, at such states:

• heavy AG;
• dekompensirovanny stagnant heart failure;
• hemodynamically significant obstacle for inflow or outflow of blood from a left ventricle (for example a stenosis of the aortal or mitral valve);
• a unilateral renal artery stenosis with the second functioning kidney;
• loss of liquid or electrolytes (including patients who receive diuretics);
• cirrhosis and/or ascites;
• when performing big surgical interventions or during anesthesia means which cause arterial hypotension.

As a rule, it is recommended to korrigirovat dehydration, a hypovolemia or deficiency of electrolytes prior to treatment (however at patients with heart failure such corrective actions should be weighed carefully concerning risk of development of a volume overload).

At patients with abnormal liver functions the response to medicament treatment Rami Sandoz can be either is strengthened, or reduced. Besides, at patients with heavy cirrhosis which is followed by hypostases and/or ascites activity renin-angiotenzinovoy of a system can be essential raised; therefore during treatment of these patients it is necessary to show extra care.

Treatment of persistent heart failure after a myocardial infarction

Patients with risk of cardiac or cerebral ischemia in case of acute arterial hypotension. The initial stage of treatment demands special medical control.

Surgical interventions. It is recommended to stop treatment by APF inhibitors, such as ramiprit if it is possible, in 1 day prior to surgical intervention.

Patients of advanced age. Elderly people can have more expressed reaction to APF inhibitors. At the beginning of their treatment it is recommended to estimate renal function.

Control of function of kidneys. Function of kidneys should be estimated to and during treatment and to constantly adjust a dose, especially in the first weeks of therapy. In the presence of damage of kidneys especially careful observation is necessary. There is a risk of deterioration in function of kidneys, especially at patients with stagnant heart failure or after renal transplantation.

Quincke's disease. At patients who were treated by APF inhibitors, including ramiprit, it was reported about a possibility of a Quincke's disease. In case of a Quincke's disease the administration of medicament should be stopped. To immediately appoint emergency treatment. Patients have to be under control of the doctor not less than 12-24 h before total disappearance of symptoms.

At patients who were treated by APF inhibitors, cases of a Quincke's disease of intestines noted. Patients complained of an abdominal pain (with or without nausea/vomiting); in certain cases there was also a Quincke's disease of the person. Symptoms of a Quincke's disease of intestines disappeared after APF inhibitor phase-out.

Anaphylactic reactions during desensitization. Probability and weight of anaphylactic and anaphylactoid reactions to poison of insects and other allergens increase at intake of APF inhibitors. Before desensitization it is necessary to consider the possibility of the temporary termination of reception of a ramipril.

Hyperpotassemia. At some patients receiving APF inhibitors, including ramiprit, noted a hyperpotassemia. The risk of emergence of a hyperpotassemia is higher for patients with a renal failure, 70 years, for patients with uncontrollable diabetes, for receiving potassium salts, kaliysberegayushchy diuretics and also other active agents which increase potassium content, or at such states as dehydration, a sharp warm decompensation, a metabolic acidosis are aged more senior. If the combined use of these medicaments is reasonable, then continuous monitoring of level of potassium in blood plasma is recommended.

Ethnic differences. APF inhibitors cause a Quincke's disease in patients of negroid race more often, than in the Caucasian. The same as at use of other APF inhibitors, ramiprit it can be less effective for decrease in the ABP level at patients of negroid race. It can be caused by the fact that at patients of negroid race with AG AG with low activity of renin develops more often.

Neutropenia/agranulocytosis. Cases of a neutropenia/agranulocytosis and also thrombocytopenia and anemia revealed seldom. There were messages about a possibility of oppression of marrow. It is recommended to control quantity of white cells in blood for identification of a possible leukopenia. The thicket should carry out monitoring at an initial stage of treatment and at patients with renal failures, with accompanying collagenoses (system lupus erythematosus or a scleroderma) or if patients take other medicaments which can cause changes of a picture of blood.

Cough. At use of APF inhibitors reported about cases of the unproductive persistent cough disappearing after the therapy termination. The possibility of the cough caused by APF inhibitors should be considered when performing differential diagnosis of cough.

Use during pregnancy and feeding by a breast. Pregnancy. Drug Rami Sandoz is contraindicated during pregnancy (see CONTRAINDICATIONS). Thus, it is necessary to exclude pregnancy before an initiation of treatment. It is necessary to avoid pregnancy if treatment by APF inhibitors is obligatory. If the patient is going to become pregnant, it is necessary to stop treatment by APF inhibitors, that is to replace them with other type of treatment.

If the patient became pregnant during treatment, medicament use Rami Sandoz needs to be replaced with therapy without APF inhibitors as soon as possible.

Feeding by a breast. Because of the shortage of information on use of a ramipril during feeding by a breast (see. Pharmacological PROPERTIES) this medicament to the women nursing is not recommended to appoint and it is desirable to give preference to other medicines which use during a lactation is safer, especially when breastfeeding newborn or premature babies.

Children. Rami Sandoz is not recommended to use medicament at children (aged up to 18 years) as data on efficiency and safety of this medicament for such patients are not enough.

Ability to influence speed of response at control of vehicles or work with other mechanisms. Some side effects (for example symptoms of decrease in the ABP, such as dizziness) can break ability of the patient to concentration of attention and reduce the speed of its reaction that is risky in situations when these qualities are of especially great importance (for example at control of vehicles or work with other mechanisms).

It in an initiation of treatment, as a rule, is possible

or upon transition from therapy by other medicaments on medicament treatment Rami Sandoz. After reception of the first dose or further increase in a dose it is undesirable to run the vehicle or to work with mechanisms within several hours.

Interaction

Contraindicated combinations. procedures of extracorporal therapy as a result of which there is a contact of blood with negatively charged surfaces, such as dialysis or haemo filtration using certain membranes with high intensity of a stream (for example membranes from polyacrylonitrile) and LDL-afereza using dextran sulfate — owing to the increased risk of heavy anaphylactoid reactions. if such treatment is necessary, it is necessary to consider a question of use of other type of dialysis membranes or other class of antihypertensive drugs.

Unrecommended combinations. The potassium salts, heparin, kaliysberegayushchy diuretics and other medicaments increasing potassium level in blood plasma (including antagonists of angiotensin ІІ, Trimethoprimum, takrolimus, cyclosporine): there can be a hyperpotassemia therefore it is necessary to carry out carefully monitoring of level of potassium in blood plasma.

to Apply

with care. Antihypertensive medicaments (for example diuretics) and other means which can reduce the ABP level (for example nitrates, tricyclic antidepressants, anesthetics, ethanol, Baclofenum, alfuzozin, docsazozin, Prazozinum, tamsulozin, terazozin): it is possible to expect strengthening of hypotensive effect.

Angiotonic sympathomimetics and other substances (for example Isoproterenolum, Dobutaminum, a dopamine, epinephrine) which can reduce expressiveness of antihypertensive effect of a ramipril: control of the ABP is recommended.

Allopyrinolum, immunosuppressants, corticosteroids, procaineamide, cytostatics and other substances which can change quantity of cells in blood: the increased probability of hematologic reactions.

Salt of lithium: APF inhibitors reduce lithium excretion therefore the probability of lithium toxicity can increase. It is recommended to control lithium level.

Anti-diabetic drugs, including insulin: hypoglycemic reactions are possible. Control of level of glucose in blood plasma is recommended.

NPVP and acetylsalicylic acid: it is possible to expect decrease in antihypertensive effect of a ramipril. Besides, the combined use of APF and NPVP inhibitors can be followed by the increased risk of deterioration in function of kidneys and increase in level of potassium in blood plasma.

Food essentially does not influence medicament absorption.

Salt. The increased use of salt can reduce expressiveness of antihypertensive action of a ramipril.

Specific desensitization. Owing to inhibition of APF the probability of emergence increases and weight of anaphylactic and anaphylactoid reactions to poison of insects increases. It is considered that such effect can also develop and concerning other allergens.

Overdose

overdose Symptoms inhibitors apf can include an excessive peripheral vazodilatation (with the profound arterial hypotension, shock), bradycardia, electrolytic disturbances, a renal failure. the condition of the patient should be controlled carefully. symptomatic and maintenance therapy is appointed: primary detoxication (gastric lavage, purpose of sorbents) and means for restoration of hemodynamic stability, including agonists α1-адренорецепторов or angiotensin іі (Angiotensinamidum). ramiprilat, the active metabolite of a ramipril, is badly brought out of an organism by a hemodialysis.

Storage conditions

At a temperature up to 25 °C in original packing.

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