Pharmacological properties

Pharmacodynamics. ii angiotensin — the main vasoactive hormone the system renin-angiotensin-aldosteronovoy (raas) playing a role in the pathophysiological mechanism of development ag, heart failure and other cardiovascular diseases. it is also involved in pathogenesis of a hypertrophy and defeat of bodies. the main physiological effects of ii angiotensin, such as vasoconstriction, stimulation of secretion of Aldosteronum, regulation of a salt and water homeostasis and stimulation of growth of cells, happen to participation of receptors of type 1 (at1).

Pharmakodinamichesky effects. Kandesartana tsileksetit is the medicament predecessor suitable for intake. It quickly turns into active agent, kandesartan, by radio hydrolysis during absorption in a digestive tract. Kandesartan is the antagonist of receptors of angiotensin II (APA II) selection concerning receptors of AT ₁ , with dense binding and slow detachment from a receptor. The activity of agonist is unusual for it.

Kandesartan does not brake APF turning angiotensin I into angiotensin II and destroys bradykinin. Influence on APF and strengthening of bradykinin or R.V substance controlled clinical trials in which compared kandesartan to APF inhibitors is noted, the frequency of cough was lower at the patients accepting a kandesartan tsileksetit. Kandesartan does not contact receptors of other hormones and does not block the ion channels important for regulation of a cardiovascular system. The antagonism to angiotensin II receptors (AT ₁ ) leads to dose-dependent increase in plasma levels of renin, angiotensin I and II and also to decrease in plasma concentration of Aldosteronum.

Clinical performance and safety. AG. At AG kandesartan causes dose-dependent long-term decrease in the ABP. Antihypertensive action takes place due to reduction of system peripheric resistance without reflex increase in ChSS. Instructions on the serious or strengthened arterial hypotension after reception of the first dose or on a withdrawal after the termination of treatment are absent.

After reception of a single dose of a kandesartan tsileksetit the beginning of antihypertensive effect in most cases it is observed during 2 h. At long-term treatment the greatest decrease in the ABP at all doses is usually reached for 4 weeks and remains in the course of long-term therapy. According to data of the metaanalysis, the average additional effect at increase in a dose from 16 to 32 mg of 1 times a day was insignificant. In view of interindividual differences, at some patients it is possible to expect more expressed, than average, effect. Kandesartana tsileksetit on condition of reception of 1 times a day provides effective and smooth decrease in the ABP during 24 h with insignificant difference between the maximum and minimum effects during a dosing interval. At use of a kandesartan of a tsileksetil together with a hydrochlorothiazide the additional decrease in the ABP is noted. The enhanced antihypertensive effect is also reached if tsileksetit a kandesartan to combine with amlodipiny or felodipiny.

to the Medicines blocking RAAS, svoystven less significant antihypertensive effect at black patients (which usually make population with the low level of renin), than at representatives of other races. It is also characteristic of a kandesartan.

Kandesartan strengthens a renal blood stream and/or does not influence or increases glomerular filtration rate due to reduction of vascular resistance in kidneys and fraction of filtration. It is known that at patients with AG and diabetes of the II type and a microalbuminuria antihypertensive treatment of a kandesartan tsileksetily reduced albumine discharge with urine. At present there are no influences of a kandesartan on progressing of a diabetic nephropathy given relatively.

Heart failure. Treatment of a kandesartan tsileksetily reduces lethality, reduces the number of hospitalization concerning heart failure and expressiveness of symptoms at patients with systolic dysfunction of a left ventricle that was shown during the "Kandesartan in Heart Failure — Assessment of Decrease in Lethality and Incidence" program (CHARM).

In the research CHARM-Alternativa the composite final point of lethality from a cardiovascular disease or the first hospitalization concerning the chronic heart failure (CHF) was much less at treatment kandesartany in comparison with placebo (the relative risk decreased by 23%). The composite final point of lethality for any reasons or the first hospitalization concerning HSN was also considerably reduced in group of a kandesartan, the absolute difference made 6%.

Both components of these composite final points — the lethality and incidence (hospitalization concerning HSN) — demonstrate in favor of favorable effect of a kandesartan. Treatment of a kandesartan tsileksetily led to improvement of a functional class on NYHA (r =0.008).

composite final point of lethality from a cardiovascular disease or the first hospitalization concerning HSN was considerably reduced

In a research of CHARM-Plus in group of a kandesartan in comparison with placebo (the relative risk decreased by 15%). The composite final point of lethality for any reasons or the first hospitalization concerning HSN was also significantly less in group of a kandesartan, the absolute difference made 3.9%. Both components of these composite final points — the lethality and incidence — demonstrate in favor of favorable effect of a kandesartan. Treatment of a kandesartan tsileksetily led to improvement of a functional class on NYHA (r =0.02).

In the research CHARM-Sokhraneniye of significant reduction of composite final points of lethality from a cardiovascular disease or the first hospitalization concerning HSN is not reached.

Knows that the positive effect of a kandesartan was permanent, despite of age, sex and the accompanying medicament treatment. Kandesartan was also effective at patients who at the same time accepted R-blockers and APF inhibitors, at the same time the positive effect was gained irrespective of whether the patient accepted APF inhibitors in the target dose recommended by the guides to treatment. At patients with HSN and reduced systolic function of a left ventricle (fraction of emission of a left ventricle of ≤40%) kandesartan reduces the system vascular resistance and pressure of jamming of pulmonary capillaries, increases activity of renin in blood plasma and concentration of angiotensin II and also reduces Aldosteronum level.

Pharmacokinetics. Absorption and distribution. After intake of a kandesartan tsileksetit turns into active agent kandesartan. The absolute bioavailability of a kandesartan is about 40% after intake of solution of a kandesartan of a tsileksetil. The relative bioavailability of a dosage form of tablets in comparison with the same solution for intake is about 34% with very insignificant variability. The estimated absolute bioavailability of a tablet, thus, is 14%. The average peak of plasma concentration (With _max ) is reached in 3–4 h after reception of a tablet. Plasma concentration of a kandesartan linearly increases with increase in doses within the therapeutic range of dosing. Sexual differences in pharmacokinetics of a kandesartan are not revealed. AUC of a kandesartan does not experience significant changes under the influence of food. Kandesartan substantially contacts proteins of blood plasma — over 99%. The imaginary volume of distribution of a kandesartan is 0.1 l/kg.

Bioavailability of a kandesartan does not change under the influence of food.

Metabolism and removal. Kandesartan is brought mainly in not changed view with urine and bile, and only in an insignificant measure — due to hepatic metabolism (CYP 2C9). Proceeding from these in vitro of researches, interaction in vivo with medicaments which metabolism depends on isoenzymes of CYP 1A2, 2A6, 2C9, 2C19, 2D6, 2E1 or 3A4 of P450 cytochrome is not expected. Final T _½ kandesartana makes about 9 h. There is no cumulation of medicament after multiple dose.

General plasma clearance of a kandesartan approximately is 0.37 ml/min. with renal clearance about 0.19 ml/min. Removal by kidneys of a kandesartan happens both by glomerular filtration, and by means of active canalicular secretion. After intake marked by a radioisotope ¹⁴ From a kandesartan of a tsileksetil about 26% of a dose it is removed with urine in the form of a kandesartan and 7% — in the form of an inactive metabolite whereas about 56% of a dose reveal in Calais in the form of a kandesartan and 10% — in the form of an inactive metabolite.

Pharmacokinetics at special categories of patents. At elderly people (65 years are more senior) With _max and AUC of a kandesartan increased approximately by 50 and 80% respectively in comparison with young people. However reaction of the ABP and frequency of the undesirable phenomena were similar after reception of a dose of the medicament Kasark by patients of young and advanced age.

At patients with a slight and moderate renal failure With _max and AUC of a kandesartan increased at repeated reception approximately by 50 and 70% respectively, but T _½ remained invariable in comparison with patients with normal function of kidneys. Corresponding changes at patients with a heavy renal failure made about 50 and 110% respectively.

Final T _½ a kandesartana was approximately doubled at patients with a heavy renal failure. The patients who are on a hemodialysis had close to an indicator AUC of a kandesartan at patients with a heavy renal failure.

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In two researches which included patients with a slight and moderate liver failure, noted increase of average AUC of a kandesartan approximately for 20% in one research and for 80% — in another. Experience of use of medicament for patients with a heavy liver failure is absent.

Indication

Treatment essential ag at adults.

Treatment of adult patients with heart failure and disturbance of systolic function of a left ventricle (fraction of emission of a left ventricle of ≤40%) as additional therapy to APF inhibitors or in case of intolerance of APF inhibitors.

Use

to Accept

inside.

Kasark should accept

1 time a day irrespective of meal.

Meal does not affect bioavailability of a kandesartan.

cannot be divided by

Tablet of 8 mg, 16 mg and 32 mg into parts therefore in need of purpose of a kandesartan of a tsileksetil in a dose of 4 mg it is necessary to use the medicine giving an opportunity of dosing of a kandesartan of a tsileksetil of 4 mg.

Dosing at AG. The recommended initial dose and a usual maintenance dose of the medicament Kasark makes 8 mg of 1 times a day. In most cases the antihypertensive effect is reached during 4 weeks. Some patients with insufficient control of the ABP can raise a dose to 16 mg of 1 times a day and a maximum up to 32 mg of 1 times a day. Therapy demands correction according to reaction of the ABP.

Kasark can also be applied together with other antihypertensive medicaments (see CONTRAINDICATIONS, SPECIAL INSTRUCTIONS, INTERACTIONS, PHARMACOLOGICAL PROPERTIES). It is shown that addition of a hydrochlorothiazide provides additional antihypertensive effect with different doses of the medicament Kasark.

Use for patients of advanced age. Initial dose adjustment at use for patients of advanced age is not necessary.

Use for patients with reduction of intravascular volume of the circulating liquid. Use of an initial dose of 4 mg can be considered at patients with risk of developing arterial hypotension, such as patients with possible dehydration (see. Special INSTRUCTIONS).

Use in a renal failure. An initial dose at patients with a renal failure, including patients on a hemodialysis, are 4 mg. The dose should be selected according to treatment response. Experience of use of medicament for patients with very heavy or terminal renal failure (clearance of creatinine of 15 ml/min.) is limited (see. Special INSTRUCTIONS).

Use in a liver failure. The initial dose of 4 mg of 1 times a day is recommended to patients with a slight and moderate liver failure. The dose can be adjusted according to treatment response. Kasark is contraindicated to patients with a heavy liver failure and/or a cholestasia (see CONTRAINDICATIONS, PHARMACOLOGICAL PROPERTIES).

Use for patients of negroid race. The antihypertensive effect of a kandesartan is less significant at black patients, than at the patients belonging to other races. Therefore, the need for increase in a dose of the medicament Kasark and the accompanying therapy for control of the ABP can arise more often at patients of negroid race, than at representatives of other races (see. Pharmacological PROPERTIES).

Dosing in heart failure. The usual recommended initial dose of a kandesartan of a tsileksetil represents 4 mg of 1 times a day. Increase to a target dose of 32 mg of 1 times a day (maximum dose) or the maximum tolerable dose happens due to doubling of a dose to intervals not less than 2 weeks (see. Special INSTRUCTIONS). Inspection of patients with heart failure always has to include assessment of function of kidneys, including monitoring of level of creatinine and potassium in blood plasma.

Kasark can be applied together with other medicines to treatment of heart failure, including APF inhibitors, blockers of β-adrenoceptors, diuretics and a digitalis or a combination of these medicines.

Combination of APF inhibitors, kaliysberegayushchy diuretics (for example Spironolactonum) and the medicament Kasark is not recommended to

, and it should be applied only after careful assessment of potential benefits and risks (see. Special INSTRUCTIONS, SIDE EFFECTS, PHARMACOLOGICAL PROPERTIES).

Special categories of patients. Initial dose adjustment is not necessary at use for patients of advanced age or patients with intravascular dehydration or a renal failure or a slight or moderate liver failure.

Children. Safety and efficiency of use of the medicament Kasark for children from the birth up to 18 years for treatment of heart failure are not established. Data are absent.

Contraindication

Hypersensitivity to a kandesartan to a tsileksetil or any of medicament excipients. abnormal liver function of heavy degree and/or cholestasia. to patients with diabetes or a renal failure (glomerular filtration rate of 60 ml/min. / 1.73 sq.m) tsileksetit simultaneous use of a kandesartan also the medicaments containing aliskiren, contraindicated.

Pregnant women or women planning pregnancy (see Use during pregnancy and feeding by a breast).

Side effects

Lecheniye ag. the undesirable reactions noted during controlled clinical trials of a kandesartan of a tsileksetil were easy and tranzitorny. communication of the general frequency of by-effects with a dose or age is noted. the quantity of cases of cancellation of treatment because of emergence of by-effects was similar at treatment of a kandesartan tsileksetily (3.1%) and placebo (3.2%).

side reactions at use of a kandesartan of a tsileksetil defined

When carrying out the generalized analysis of these clinical trials with participation of patients with AG on the basis of the undesirable phenomena which frequency at least for 1% exceeded the frequency of side reactions at placebo use. Dizziness / vertigo, the headache and respiratory infections were the most frequent undesirable reactions.

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used the following determination of frequency: very often (≥1/10), it is frequent (from ≥1/100 to 1/10), infrequently (from ≥1/1000 to 1/100), is rare (from ≥1/10 000 to 1/1000) and is very rare (1/10,000).

following side reactions at use of a kandesartan of a tsileksetil Are possible

:

an infection and invasion: often — respiratory infections.

from blood and lymphatic system: very seldom — a leukopenia, a neutropenia, an agranulocytosis.

from a metabolism and food: very seldom — a hyperpotassemia, a hyponatremia.

from nervous system: often — dizziness / vertigo, a headache.

Respiratory, thoracic and mediastinal disturbances: very seldom — cough.

from a digestive tract: very seldom — nausea.

from a gepatobiliarny system: very seldom — increase in level of liver enzymes, an abnormal liver function, hepatitis.

from skin and hypodermic cellulose: very seldom — a Quincke's disease, rash, a small tortoiseshell, an itching.

from a musculoskeletal system: very seldom — a dorsodynia, an arthralgia, myalgia.

from kidneys and urinary tract: very seldom — deterioration in function of kidneys, including OPN at sensitive patients.

Results of laboratory analyses: in most cases did not fix clinically significant influence of the medicament Kasark on usual laboratory indicators. As well as at use of other RAAS inhibitors the insignificant decrease in level of hemoglobin is noted. Usually for the patients accepting Kasark there is no need for continuous monitoring of laboratory indicators. However at patients with a renal failure the periodic monitoring of levels of potassium and creatinine in blood plasma is recommended.

Treatment of heart failure. The profile of side undesirable reactions of the medicament Kasark at patients with heart failure corresponded to pharmacological properties of medicament and the state of health of patients. The undesirable phenomena, such as hyperpotassemia, arterial hypotension and renal failure, were most often observed at patients 70 years sick with diabetes or the patients accepting other medicines influencing RAAS, in particular APF inhibitors and/or Spironolactonum are aged more senior.

following side reactions at use of a kandesartan of a tsileksetil Are possible

:

from blood and lymphatic system: very seldom — a leukopenia, a neutropenia and an agranulocytosis.

from a metabolism and food: often — a hyperpotassemia; very seldom — a hyponatremia.

from nervous system: very seldom — dizziness, a headache.

from vessels: often — arterial hypotension.

Respiratory, thoracic and mediastinal disturbances: very seldom — cough.

from a digestive tract: very seldom — nausea.

from a liver and biliary tract: very seldom — increase in level of liver enzymes, an abnormal liver function, hepatitis.

from skin and hypodermic cellulose: very seldom — a Quincke's disease, rashes, urticaria, an itching.

from a skeletal and muscular system and connective tissue: very seldom — a dorsodynia, an arthralgia, myalgia.

from kidneys and urinary tract: often — a renal failure, including a renal failure at sensitive patients.

Results of laboratory analyses: at the patients accepting a kandesartan tsileksetit according to the indication heart failure, the hyperpotassemia and a renal failure are often noted. Periodic monitoring of levels of creatinine and potassium in blood plasma is recommended (see. Special INSTRUCTIONS).

Special instructions

Double blockade raas. there are proofs that simultaneous use of inhibitors apf and blockers of receptors of ii angiotensin or an aliskiren increases risk of developing arterial hypotension, a hyperpotassemia and deterioration in function of kidneys (including opn). therefore double blockade raas by means of the combined use of inhibitors apf and blockers of receptors of ii angiotensin or an aliskiren is not recommended. if therapy by double blockade is considered necessary absolutely, it should be carried out only under observation of the expert and on condition of frequent careful monitoring of function of kidneys, electrolytes and hell.

APF Inhibitors and blockers of receptors of angiotensin II should not be applied at the same time to patients with a diabetic nephropathy.

Renal failure. As well as at use of other means braking RAAS it is possible to expect change of function of kidneys at the sensitive patients accepting a kandesartan tsileksetit.

tsileksetit

At use of a kandesartan at patients with AG and the renal failure recommends periodic monitoring of level of potassium and creatinine in blood plasma.

Experience of use of medicament for patients with very heavy or terminal renal failure (clearance of creatinine of 15 ml/min.) is limited to

. Such patients should select a dose of the medicament Kasark carefully, carrying out careful monitoring of the ABP. Inspection of patients with heart failure has to include periodic assessment of function of kidneys, especially at patients of advanced age (of 75 years) and also at patients with renal failures. During selection of a dose of a kandesartan of a tsileksetil the monitoring of level of creatinine and potassium in blood plasma is recommended. Clinical trials of heart failure did not include patients with creatinine level in blood plasma of 265 µmol/l (3 mg/dl).

Accompanying therapy using APF inhibitors in heart failure. The risk of side reactions, especially arterial hypotension, a hyperpotassemia and deterioration in function of kidneys (including OPN), can increase at use of a kandesartan of a tsileksetil in a combination with APF inhibitors. The triple combination of APF inhibitor, the antagonist of receptors of mineralokortikoid and a kandesartana of a tsileksetil is also not recommended. Use of these combinations has to be carried out only under observation of the expert and on condition of frequent careful monitoring of function of kidneys, electrolytes and the ABP.

should not apply APF inhibitors along with blockers of receptors of angiotensin II to patients with a diabetic nephropathy.

Hemodialysis. Against the background of dialysis of the ABP can be especially sensitive to blocking of AT ₁ - receptors as a result of reduction of volume of blood plasma and activation of RAAS. Thus, to the patients who are on a hemodialysis, it is necessary to select a dose of the medicament Kasark carefully, carrying out monitoring of the ABP.

Renal artery stenosis. The medicines influencing RAAS, including the MACAW of II, can increase urea level in blood and creatinine in blood plasma at patients with a bilateral renal artery stenosis or a stenosis of an artery of the only kidney.

Transplantation of a kidney. Experience of use of the medicament Kasark for patients from the kidney which is recently postponed transplantation is limited.

Arterial hypotension. Patients with heart failure during the Kasark medicament treatment can have an arterial hypotension. It can also develop at patients with AG and intravascular dehydration as a result of reception of high doses of diuretics. It is necessary to begin therapy with care and to take measures concerning correction of a hypovolemia.

Anesthesia and surgical interventions. The patients accepting the MACAW of II during anesthesia and surgical interventions can have an arterial hypotension as a result of blockade of RAAS. Very seldom arterial hypotension can be expressed and demand in/in input of the fluid and/or use of vasoconstrictors.

Stenosis of aortal and mitral valves (subaortic hypertrophic stenosis). As well as at use of other vazodilatator, the special care is shown to patients with hemodynamically significant stenosis of aortal or mitral valves or a subaortic hypertrophic stenosis.

Primary hyper aldosteronism. Patients with primary hyper aldosteronism in most cases do not react to the antihypertensive medicines operating thanks to braking of RAAS. Thus, use of the medicament Kasark in this population is not recommended.

Hyperpotassemia. Simultaneous use of the medicament Kasark with kaliysberegayushchy diuretics, the potassium drugs, kaliysoderzhashchy substitutes of salt or other medicines capable to increase potassium levels (for example heparin), can lead to increase in plasma level of potassium at patients with AG. It is necessary to carry out monitoring of level of potassium properly.

patients with heart failure accepting Kasark can have a hyperpotassemia. Periodic monitoring of level of potassium in blood plasma is recommended. The combination of APF inhibitors, kaliysberegayushchy diuretics (for example Spironolactonum) and the medicament Kasark is not recommended and it can be applied only after careful assessment of potential benefits and risks.

General. At patients, a vascular tone and which function of kidneys depend mainly on activity of RAAS (for example patients with heavy stagnant heart failure or a basic disease of kidneys, including a renal artery stenosis) treatment using other medicines influencing this system was connected with acute arterial hypotension, an azotemia, an oliguria or is rare — with OPN. The possibility of similar effects cannot be excluded at use of MACAW of II. As well as any antihypertensive drug, excessive decrease in the ABP at patients with an ischemic cardiopathy or an ischemic cerebrovascular disease can lead to a myocardial infarction or a stroke.

Antihypertensive effect of a kandesartan can amplify other medicines which have property to lower the arterial blood pressure irrespective of, they are appointed as antihypertensive medicaments or are applied according to other indications.

Kasark contains lactose. Patients with rare hereditary forms of intolerance of a galactose, a lactose intolerance of Lapp or malabsorption of glucose galactose cannot accept this medicine.

Pregnancy. Use of MACAW ІІ should not be begun during pregnancy. Except for cases when continuation of therapy of MACAW ІІ is considered necessary extremely, the patients planning pregnancy should appoint alternative antihypertensive treatment with the established safety profile for use during pregnancy. If pregnancy is diagnosed, treatment of MACAW ІІ should be stopped immediately and if it is necessary, to begin alternative therapy.

an opportunity to become pregnant is estimated by

At patients in the postmenarkhealny period on the general basis. It is necessary to provide the relevant information and/or to take measures for prevention of risk of influence of medicament during pregnancy (see CONTRAINDICATIONS and Use during pregnancy and feeding by a breast).

Use during pregnancy and feeding by a breast. Tsileksetit use of a kandesartan during pregnancy contraindicated. Kandesartana tsileksetit it is not recommended for use during feeding by a breast.

Pregnancy. Epidemiological proofs of risk of teratogenecity after exposure of APF inhibitors in І a trimester of pregnancy do not allow to make the final conclusion, however slight increase of risk cannot be excluded. As controlled epidemiological data on risk at use of MACAW ІІ are absent, similar risks can exist also for this class of medicines. Except for cases when continuation of therapy of MACAW ІІ is considered necessary extremely, the patients planning pregnancy should appoint alternative antihypertensive treatment with the established safety profile for use during pregnancy. If pregnancy is diagnosed, treatment by medicaments MACAWS ІІ should be stopped immediately and if necessary to begin alternative therapy.

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Newborn whose mothers received the MACAW ІІ, needs careful observation regarding arterial hypotension.

Feeding by a breast. As there is no information on use of the medicament Kasark during feeding by a breast, medicament is not recommended for use. It is necessary to give preference to alternative methods of treatment with better the studied safety profiles during feeding by a breast, especially newborn or premature children.

Children. Safety and efficiency of use of the medicament Kasark for children are not established.

Ability to influence speed of response at control of vehicles or work with other mechanisms. Researches concerning influence of a kandesartan on ability to run vehicles and to work with other mechanisms were not conducted. However it is necessary to take into account that during the Kasark medicament treatment the dizziness or increased fatigue develop.

Interaction

Drugs which were studied in clinical pharmacokinetic trials include a hydrochlorothiazide, warfarin, digoxin, oral contraceptives (that is ethinylestradiol/levonorgestrel), glibenclamide, nifedipine and enalapril. clinically significant pharmacokinetic interaction with these medicines is not revealed.

Simultaneous use of kaliysberegayushchy diuretics, medicaments of potassium, kaliysoderzhashchy substitutes of salt or other medicines (for example heparin) can increase potassium levels. Monitoring of level of potassium should be carried out properly (see. Special INSTRUCTIONS).

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It was reported about reversible increase in plasma concentration of lithium and toxicity during a concomitant use of lithium and APF inhibitors.

Similar effect can be noted by

at use of MACAW of II. Use of a kandesartan with lithium is not recommended. If need of a combination is confirmed, careful monitoring of plasma level of lithium is recommended.

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At simultaneous introduction of MACAW of II with NPVP (for example selection TsOG-2 inhibitors, acetylsalicylic acid (3 g/days) and non-selective NPVP) easing of antihypertensive effect can be observed.

As well as at use of APF inhibitors, the concomitant use of MACAW of II and NPVP can lead to increase in risk of deterioration in function of kidneys, including possible OPN and increase in level of potassium in blood plasma, in particular at patients with the function of kidneys weakened already in an initiation of treatment. The combination should be applied with care, especially at patients of advanced age. The patient needs to carry out properly hydration and it is necessary to pay attention to monitoring of function of kidneys after the beginning of the accompanying therapy and periodically further.

Data of clinical trial demonstrate that double blockade of RAAS by means of the combined use of APF inhibitors and blockers of angiotensin II or an aliskiren is connected with the bigger frequency of by-effects, such as arterial hypotension, hyperpotassemia and deterioration in function of kidneys (including OPN), in comparison with the use of medicine in monotherapy influencing RAAS.

Overdose

Symptoms: considering pharmacological properties of drug, symptomatic arterial hypotension and dizziness will probably be the main manifestation of overdose. in some cases overdoses (up to 672 mg of a kandesartan of a tsileksetil) it is reported about recovery of patients without consequences.

Treatment: if symptomatic arterial hypotension develops, it is necessary to appoint symptomatic treatment and to carry out monitoring of vital signs. The patient should give a dorsal decubitus with lifted upside down. If it is not enough, it is necessary to increase blood plasma volume by means of infusion, for example 0.9% of solution of sodium of chloride. If above-mentioned actions are not enough, it is possible to apply sympathomimetic medicines. Kandesartan is not brought by means of a hemodialysis.

Storage conditions

In original packing at a temperature not above 25 °C.