Kasark

General characteristics. Structure:

Active ingredient: 1 tablet contains a kandesartan of a tsileksetil, in terms of 100% substance, 16 mg or 32 mg;

excipients: calcium of a karmeloz; starch corn; hydroxypropyl cellulose; lactose, monohydrate; magnesium stearate; polyethyleneglycol (PEG 8000).

Pharmacological properties:

Pharmacodynamics. Angiotensin ІІ is primary vasoactive hormone system renin-angiotensin-aldosteronovoy, it plays a role in a pathophysiology of the arterial hypertension (AH), heart failure and other cardiovascular disturbances. The main physiologic effects of angiotensin ІІ, such as narrowing of blood vessels, stimulation of secretion of Aldosteronum, regulation of a salt and water homeostasis and stimulation of growth of cells, are mediate because of a receptor of type 1 (AT1).

Kandesartan is an antagonist of a receptor of angiotensin ІІ, the selection for        AT1-receptors, with strong linkng with a receptor and slow dissociation with it. It has no activity of an agonist. Kandesartan does not inhibit APF which turns angiotensin І into angiotensin ІІ and bradikinin destroys. Influence on APF and potentiation of bradikinin or substance P are absent. When comparing a kandesartan with APF inhibitors development of cough occurs less often at patients who receive кандесартан.

Kandesartan does not contact receptors of other hormones and does not block ion channels which, as we know, play a role in cardiovascular regulation. Antagonism of AT1-receptors leads to dozozavisimy increase in level of a renin of plasma, angiotensin levels Іи angiotensin ІІ, and also to decrease in concentration of Aldosteronum in a blood plasma.

Arterial hypertension.

At arterial hypertension кандесартан leads to dozozavisimy, long-term decrease in AT. Anti-hypertensive activity is caused by reduction of obshchegoperiferichesky resistance which is not followed by reflex increase in heart rate. Points nothing to the serious or strengthened AG after reception of the first dose or to reactive effect after the treatment termination.

After reception of a single dose of a kandesartan of a tsileksetil the beginning of anti-hypertensive effect usually comes within 2 hours. At continuous treatment the greatest decrease in the ABP with any dose is usually reached within 4 weeks and supported at long-term treatment. According to data of meta-analysis, the average additional effect of increase in a dose from 16 to 32 mg was small once a day. Considering interindividual variability, at some patients it is possible to expect more than average effect.

At use of a kandesartan of a tsileksetil once for days it provides effective and uniform decrease in the ABP for 24 hours, with a small difference between the maximum and minimum effect during a dosing interval.

Kandesartan raises a renal blood stream of blood and/or does not render effect on the speed of glomerular filtering, or raises it while the vascular resistance and filtrational function is reduced.

At the patients with arterial hypertension suffering from Iitipa diabetes mellitus                12 weeks treatment of a kandesartan tsileksetily a dose of 8-16 mg does not render side effect on the level of glucose of blood or on a lipidic profile.

Heart failure.

Treatment of a kandesartan tsileksetily reduces mortality, reduces hospitalization level because of heart failure and eliminates symptoms at patients with disturbance of systolic function of a left ventricle.

Positive influence of a kandesartan on decline in mortality from cardiovascular diseases or the frequency of the first hospitalization because of heart failure was invariable irrespective of age, sex and the accompanying treatment. Kandesartan is also effective at patients who at the same time accept both b-blockers, and APF inhibitors; the positive effect is reached irrespective of whether the patient accepts APF inhibitors in a target dose.

At patients with SN and disturbance of systolic function of a left ventricle (fraction of emission of a left ventricle of £40%) кандесартан reduces the system vascular resistance and pulmonary capillary pressure, increases activity of a renin and concentration of angiotensin ІІ in plasma, and also reduces Aldosteronum levels.

Pharmacokinetics. Absorption and distribution.

Kandesartana tsileksetit is the pro-medicine suitable for oral administration. It quickly turns into active agent - кандесартан – by ester hydrolysis during absorption from digestive tract, densely contacts AT1-receptors and slowly dissociates. Absolute bioavailability of a tablet makes 40%. The average maksimalnayakontsentration in blood serum (Cmax) is reached in 3-4 hours after reception of a tablet. Concentration of a kandesartan grow in serum linearly with increase in doses within a therapeutic dose.

The difference in the pharmacokinetics of a kandesartan connected with a floor is not observed. Meal concentration in serum – time" has no significant effect on the area under a curve "(AUC).

Kandesartan highly contacts proteins of plasma (more than 99%). The visible volume of distribution of a kandesartan makes 0,1 l/kg.

Metabolism and removal from an organism.

Kandesartan, mainly, is brought from an organism with urine and bile in not changed look and only in an insignificant measure is brought by hepatic metabolism.

The elimination half-life of a kandesartan makes about 9 hours. After reception of repeated doses of cumulation of drug in an organism does not occur.

The general plasma clearance of a kandesartan makes about 0,37 ml/min., and renal clearance – about 0,19 ml/min. Renal excretion of a kandesartan is carried out by both glomerular filtering, and active tubular secretion. After reception of a peroral dose of the 14C-marked 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 though about 56% of a dose are defined in excrements in the form of a kandesartan and 10% – in the form of an inactive metabolite.

Pharmacokinetics at special categories of patients.

At elderly people (65 years are more senior) Cmax and AUC of a kandesartan are raised approximately for 50% and 80% respectively, in comparison with young patients. However reaction of the ABP and frequency of emergence of side effects is identical after reception of the established dose of КасаркаÒу of young patients and elderly people.

At patients with a renal failure from easy to moderate severity, in comparison with patients with normal renal function, Cmax and AUC of a kandesartan increases after multiple dose of doses approximately by 50% and 70% respectively whereas the elimination half-life of drug remains invariable. Corresponding changes at patients with a heavy renal failure make about 50% and 110% respectively, and the elimination half-life of drug increases twice.

The indicator of AUC of a kandesartan at the patients who are on a hemodialysis is similar to that which was observed at patients with a heavy renal failure.

At patients with a liver failure from easy to moderate severity increase in an indicator of AUC of a kandesartan for 23% is noted.

Main physical and chemical properties:

KacapkÒ, tablets on 16 mg: tablets of white or almost white color, a round form, with a biconvex surface. On a surface of a tablet the mramornost is allowed.

KacapkÒ, tablets on 32 mg: tablets of white or almost white color, a round form, with a biconvex surface, from a risky on the one hand tablet. On a surface of a tablet the mramornost is allowed.

Indications to use:

Essential hypertensia. Heart failure and disturbance of systolic function of a left ventricle (decrease in fraction of emission of a left ventricle of £40%) as additional therapy to treatment by inhibitors of an angiotensin-converting enzyme (APF) or in case of intolerance of APF inhibitors.

Route of administration and doses:

Dosing at arterial hypertension.

The recommended initial dose of КасаркаÒи a usual maintenance dose makes 8 mg once a day. In most cases the anti-hypertensive effect is reached within 4 weeks. It is possible to increase a dose to 16 mg once a day.  If sufficient control of the arterial pressure (AP) is not reached in 4 weeks of treatment by a dose of 16 mg once a day, then it is possible to increase a dose to 32 mg once a day.

Therapy needs to be adjusted according to reaction of the ABP.

Use for patients of advanced age.

Correction of an initial dose at patients of advanced age is not necessary.

Use for patients with reduction of intravascular volume of the circulating blood.

For patients who have a risk of arterial hypotension for example for patients with possible reduction of volume of the circulating blood, it is necessary to consider an initial dose of 4 mg.

Use at a renal failure.

At patients with a renal failure, including the patients who are on a hemodialysis, the initial dose makes 4 mg. The dose should be titrated taking into account the ABP. Experience of use for patients with a heavy renal failure or a renal failure of an end-stage (the clearance of creatinine <15 ml/min.) is limited.

Use at a liver failure.

From easy to moderate severity the initial dose of drug 4 of mg is recommended to patients with a liver failure once a day. The dose needs to be korrigirovat taking into account the ABP. КасаркÒпротивопоказан to patients with a heavy liver failure and/or a cholestasia.

The accompanying therapy.

It is established that additional purpose of Hydrochlorthiazidum has the additive anti-hypertensive effect together with КасаркомÒ.

Use to patients of negroid race.

The anti-hypertensive effect of a kandesartan is less expressed at patients of negroid race to what patients of other races. Therefore, titration of a kandesartan towards increase in a dose and the accompanying therapy for control of the ABP it are required for patients of negroid race, than representatives of other races more often.

Dosing at heart failure.

The usual recommended initial dose of КасаркаÒсоставляет 4 mg once a day. Titration towards increase in a target dose of 32 mg or the most tolerable dose is carried out once a day by a dose doubling through the periods making at least 2 weeks. Inspection of patients with heart failure always has to include assessment of function of kidneys, including monitoring of creatinine and potassium of blood serum.

Kasark to apply Òможно together with other treatment concerning heart failure, including APF inhibitors, beta-blockers, diuretics and a digitalis or a combination of these medicines. The combination of APF inhibitors, kaliysberegayushchy diuretics (for example Spironolactonum) and Kasarka is recommended to Òне, and it should be applied only after careful estimation of potential advantages and risks.

Special categories of patients.

For patients of advanced age or with the reduced volume of the circulating blood, a renal or liver failure of easy and moderate severity correction of an initial dose is not necessary.

Use to children.

Safety and efficiency of use for Kasark's children of Òпри treatment of arterial hypertension and heart failure are not established.

Route of administration.

Accept inside.

Kasark to accept Òследует 1 time a day irrespective of meal.

Meal does not influence bioavailability of a kandesartan.

Features of use:

Renal failure.

As well as in a case with other drugs inhibiting renin-angiotensin-aldosteronovuyu system it is possible to expect change of renal function at the patients predisposed to it accepting KacapkÒ.

At use of КасаркаÒу of patients with the arterial hypertension (AH) and a renal failure periodic monitoring of level of potassium and creatinine in blood serum is recommended. Experience of use by the patient with a heavy renal failure or a renal failure of an end-stage (the clearance of creatinine <15 ml/min.) is limited. At these patients it is necessary to titrate attentively КасаркÒв a combination to monitoring of the ABP.

Assessment of a condition of patients with heart failure has to include periodic assessment of renal function, especially at patients of advanced age – 75 years and at patients with a renal failure are more senior. During titration of a dose of КасаркаÒрекомендуется monitoring of level of creatinine and potassium in blood serum.

The accompanying therapy by APF inhibitor at heart failure.

The risk of side effects, especially at a renal failure and a hyperpotassemia, can increase at use of a kandesartan in a combination with APF inhibitor. These patients demand regular and careful control.

Hemodialysis.

During dialysis of the ABP system renin-angiotensin-aldosteronovoy can be especially sensitive to blockade of a receptor of AT1 owing to reduction of volume of a blood plasma and activation. For the patients who are on a hemodialysis it is necessary to titrate attentively КасаркÒи carefully to control the ABP.

Renal artery stenosis.

Other medicines influencing renin-angiotensin-aldosteronovuyu system, for example APF inhibitors can increase the level of urea of blood and creatinine of blood serum at patients with a bilateral renal artery stenosis or a stenosis of the artery conducting to one kidney. The similar effect can be expected at use of antagonists of receptors of angiotensin II.

Transplantation of a kidney.

Experience of use of КасаркаÒу of the patients who recently transferred transplantation of a kidney no.

Arterial hypotension.

During treatment of КасаркомÒу of patients with heart failure there can be arterial hypotension. It can also arise at patients with AG and reduced volume of the circulating blood, for example at those patients who accept high doses of diuretics. It is necessary to begin therapy with care and to take measures for correction of a hypovolemia.

Anesthesia and surgical interventions.

At the patients receiving treatment by antagonists of receptors of angiotensin II, arterial hypotension can develop in time of anesthesia and surgical intervention owing to blockade system renin-angiotensin-aldosteronovoy. Seldom or never arterial hypotension can be so heavy that use of intravenous liquids and/or vazopressor can be required.

Stenosis of an aorta of the ilimitralny valve, subaortic hypertrophic stenosis.

As well as in a case with other vasodilators, it is necessary to be especially careful at treatment of patients who suffer from hemodynamically significant stenosis of an aorta or the mitral valve, or a subaortic hypertrophic stenosis.

Primary hyper aldosteronism.

Patients with primary hyper aldosteronism usually do not react to the anti-hypertensive medicines operating by inhibition system renin-angiotensin-aldosteronovoy. Therefore it is recommended to apply КасаркÒне.

Hyperpotassemia.

Simultaneous use of KacapkaÒc kaliysberegayushchy diuretics, potassium drugs, the salt substitutes containing potassium or other medicines capable to increase potassium level (for example heparin), can lead to increase in serumal level of potassium at patients with arterial hypertension. It is necessary to carry out monitoring of level of potassium properly.

The patients with heart failure accepting KacapkÒ can have a hyperpotassemia. Periodic monitoring of level of potassium in blood serum is recommended. The combination of APF inhibitors, kaliysberegayushchy diuretics (for example Spironolactonum) and КасаркаÒне is recommended, and it can be applied only after careful estimation of potential advantages and risks.

Obshchiyesvedeniya.

At patients, at a kotorykhsosudisty tone and function of kidneys depend preferential on activity system renin-angiotensin-aldosteronovoy (for example, patients with heavy congestive heart failure or with diseases of kidneys, including a renal artery stenosis), treatment by other medicines influencing this system was associated with acute arterial hypotension, an azotemia, an oliguria or, in rare instances, with an acute renal failure. The possibility of similar effects cannot be excluded at use of antagonists of receptors of angiotensin ІІ. As well as in a case with any other anti-hypertensive drug, excessive decrease in the ABP at patients with an ischemic cardiomyopathy or an ischemic cerebrovascular disease can lead to a myocardial infarction or a stroke.

КасаркÒне patients should accept with rare hereditary problems of intolerance of a galactose, a lactose intolerance of Lapp or malabsorption of glucose galactose.

Use during pregnancy.

Epidemiological proofs of risk of teratogenecity after exposure of APF inhibitors in the period of the I trimester of pregnancy do not allow to draw a final conclusion, however slight increase of risk cannot be excluded. As controlled epidemiological data on risk at use of antagonists of receptors of angiotensin II are absent, similar risks can exist also for this class of medicines. Except for cases when therapy using antagonists of receptors of angiotensin II is considered extremely necessary, the patients planning pregnancy need to appoint alternative anti-hypertensive treatment that has the established safety profile for use during pregnancy. If pregnancy is diagnosed, treatment using antagonists of receptors of angiotensin II should be stopped immediately and if it is necessary, to appoint alternative therapy.

It is known that therapy by antagonists of receptors of angiotensin II in the period of II and III trimesters is capable to cause a fetotoksichnost in the person (depression of function of kidneys, олигогидрамнион, a skull ossification delay) and a neonatalnuyutoksichnost (a renal failure, arterial hypotension, a hyperpotassemia). If influence of antagonists of receptors of angiotensin II состоялосьв the period of the II trimester of pregnancy, is recommended ultrasound examination of kidneys and a skull.

Newborns, whose mothers accepted antagonists of receptors of angiotensin II, demand careful observation regarding arterial hypotension.

Use during feeding by a breast.

As there is no available information concerning use of КасаркаÒв the feeding period a breast, Kasark is recommended to Òне for use, and alternative methods of treatment with better the studied safety profiles during feeding by a breast are prevailing, especially during feeding of newborn or premature children.

Ability to influence speed of response at control of motor transport or work with other mechanisms. Influence of a kandesartan on ability to manage motor transport and to use mechanisms was not studied. However it is necessary to take into account possibility during treatment by КасаркомÒартериальной of hypotension which can be followed by dizziness and increased fatigue.

Side effects:

Treatment of arterial hypertension.

Side reactions at reception of a kandesartan lungs ivremenny. The general frequency of emergence of side reactions indicates dependence on a dose or age.

The following widespread is possible (> 1/100) tsileksetit side reactions at use of a kandesartan:

From a nervous system: dizziness / вертиго, headache.

Infections and invasions: respiratory infections.

Results of laboratory researches: in general clinically significant influence of a kandesartan on laboratory indicators is not observed. At use of other inhibitors renin-angiotensin-aldosteronovoy of system is noted small decrease in level of hemoglobin. For the patients receiving KacapkÒ, continuous monitoring of laboratory indicators usually is not necessary. However patients with a renal failure are recommended to carry out periodically monitoring of level of potassium and creatinine in blood serum.

Treatment of heart failure.

The profile of side effect of a kandesartan at patients with heart failure answers pharmacological properties of this drug and the state of health of patients.

To widespread side reactions (³1/100, <1/10) belong:

Vascular disorders: arterial hypotension.

Disturbances of metabolism and food: hyperpotassemia.

From kidneys and urinary tract: renal failure.

Results of laboratory researches: increase in level of creatinine, urea and potassium. Periodic monitoring of levels of creatinine and potassium in blood serum is recommended.

Very seldom (<1/10000) at treatment of arterial hypertension and heart failure the following side reactions are possible.

From blood and lymphatic system: leukopenia, neutropenia and agranulocytosis.

Disturbances of metabolism and food: hyperpotassemia, hyponatremia.

From a nervous system: dizziness, headache.

From respiratory system: cough.

Gastrointestinal disturbances: nausea.

Gepatobiliarny disturbances: increase in levels of enzymes of a liver, abnormal liver function or hepatitis.

From skin and hypodermic cellulose: Quincke's disease, rash, small tortoiseshell, itch.

From skeletal and muscular, connecting fabric and bones: dorsodynia, arthralgia, myalgia.

From kidneys and urinary tract: disturbance of renal function, including a renal failure at patients, inclined to it.

Interaction with other medicines:

Clinically significant medicinal interaction is not revealed. Drugs which were studied included Hydrochlorthiazidum, warfarin, digoxin, oral contraceptives (ethinylestradiol/levonorgestrel), Glibenclamidum, nifedipine, enalapril.

Simultaneous use of kaliysberegayushchy diuretics, drugs of potassium, the substitutes of salt containing potassium or other medicines (for example heparin) can increase potassium level. Control of level of potassium should be exercised properly.

Perhaps reversible increase in concentration of lithium in blood serum and its toxicity during the accompanying use of lithium with APF inhibitors.

The similar effect can arise with antagonists of receptors of angiotensin II. Therefore use of a kandesartan with lithium is not recommended. If there is a confirmation of need of a combination, careful monitoring of serumal levels of lithium is recommended.

At simultaneous use of antagonists of receptors of angiotensin II with non-steroidal anti-inflammatory drugs (for example (> 3 g/days) and non-selective non-steroidal anti-inflammatory drugs) easing of anti-hypertensive effect can arise the selection TsOG-2 inhibitors, acetylsalicylic acid.

As well as in a case with APF inhibitors, simultaneous use of antagonists of receptors of angiotensin II and non-steroidal anti-inflammatory drugs can increase risk of deterioration in function of kidneys, including a possible acute renal failure and increase in level of potassium in blood serum, especially at patients with the function of kidneys weakened already in an initiation of treatment. This combination should be applied with care, especially at elderly people. Patients have to receive enough liquid, and also it is necessary to consider need of monitoring of function of kidneys after the beginning of the accompanying therapy and periodic monitoring further.

Contraindications:

Hypersensitivity to a kandesartan to a tsileksetil or to any of drug excipients. Heavy liver failure and/or cholestasia.

Use during pregnancy or feeding by a breast.

Use of drug during pregnancy is contraindicated. КасаркÒне it is recommended for use during feeding by a breast.

Children. Safety and efficiency of use of the drug КасаркÒдетям are not established.

Overdose:

Symptoms. It is possible to carry symptomatic hypotension and dizziness to the main manifestations of overdose.

Treatment. When developing symptomatic arterial hypotension it is necessary to begin a symptomatic treatment and tracking of the vital functions. The patient it is necessary to put on a back with the raised lower extremities. If it is not enough, it is necessary to increase blood plasma volume by infusion, for example, of isotonic saline solution. If above-mentioned actions are not enough, it is possible to apply symptomatic medicines.

Kandesartan is not brought by a hemodialysis.

Storage conditions:

Period of validity 2 years. To store to voriginalny packaging, at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in the blister, on 3 blisters in a pack.