Angiakand

General characteristics. Structure:

Dosage of 8 mg
1 tablet contains:
active agent: a kandesartana tsileksetit 8 mg;
excipients: starch corn prezhelatinizirovanny - 20,3 mg, croscarmellose sodium (primelloza) - 3,5 mg, lactoses monohydrate (sugar milk) - 64,5 mg, magnesium stearate - 0,7 mg, povidon-K30 - 3 mg.
Dosage of 16 mg
1 tablet contains:
active agent: a kandesartana tsileksetit 16 mg;
excipients: starch corn prezhelatinizirovanny – 23,8 mg, croscarmellose sodium (primelloza) - 5 mg, lactoses monohydrate (sugar milk) - 90 mg, magnesium stearate - 1 mg, povidon-K30 – 4,2 mg.
Dosage of 32 mg
1 tablet contains:
active agent: a kandesartana tsileksetit 32 mg;
excipients: starch corn prezhelatinizirovanny – 27,5 mg, croscarmellose sodium (primelloza) - 7 mg, lactoses monohydrate (sugar milk) - 126 mg, magnesium stearate – 1,5 mg, povidon-K30 – 6 mg.

Description:
Tablets of white or almost white color, round, biconvex.

Pharmacological properties:

Pharmacodynamics. Kandesartan is the selection antagonist of receptors of angiotensin II of 1 type (AT1 receptors), forms with them strong communication with the subsequent slow dissociation. Has vazodilatiruyushchy, hypotensive and diuretic effect. Does not show properties of an agonist (does not inhibit an angiotensin-converting enzyme (APF) and does not lead to accumulation of bradikinin or substance P, does not contact receptors of other hormones, does not block the ion channels participating in regulation of functions of cardiovascular system). Blocking of AT1 receptors of angiotensin II is resulted by compensatory dozozavisimy increase in activity of a renin, concentration of angiotensin I, angiotensin II and decrease in concentration of Aldosteronum in a blood plasma.
Arterial hypertension
The anti-hypertensive effect is caused by decrease in the general peripheric vascular resistance (GPVR), at the same time there is no influence on the heart rate (HR). Cases of the expressed arterial hypotension after reception of the first dose of drug, and also a syndrome of "cancellation" after the therapy termination are noted. The beginning of anti-hypertensive action after reception of the first dose usually develops within 2 hours. Against the background of the continuing therapy by drug in the fixed dose the maximum lowering of arterial pressure (ABP) usually is reached within 4 weeks and remains throughout all treatment.
Kandesartan raises a renal blood stream and does not change or increases a glomerular filtration rate whereas vascular resistance in kidneys and filtrational fraction decrease.
2 types do not influence concentration of glucose and a lipidic profile at patients with arterial hypertension and a diabetes mellitus. Provides a dozozavisimy smooth lowering of arterial pressure.
The age and sex do not influence efficiency of drug.
Chronic heart failure
At patients with chronic heart failure and decrease in fraction of emission of a left ventricle less than 40% reception of a kandesartan promoted decrease in OPSS and capillary pressure in lungs, to increase in activity of a renin and concentration of angiotensin II in a blood plasma, and also to decrease in concentration of Aldosteronum.

Pharmacokinetics. Kandesartan is pro-medicine for intake. Quickly (by means of radio hydrolysis) turns in pharmacological active кандесартан. Absolute bioavailability of a kandesartan after intake of solution of a kandesartan of a tsileksetil makes about 40%. Relative bioavailability of the tableted drug in comparison with peroral solution makes about 34%. Thus, settlement absolute bioavailability of the tableted form - about 14% also does not depend on meal time. The maximum concentration (Cmax) in blood serum is reached in 3-4 h. Concentration in a blood plasma increases linearly at increase in a dose in a therapeutic interval (to 32 mg). Distribution volume – 0,13 l/kg. Communication with proteins of a blood plasma – 99,8%.
It is slightly metabolized in a liver (20-30%) with the participation of an isoenzyme of P450 CYP2C9 cytochrome with formation of inactive derivative. A final elimination half-life (T1/2) - 9 h. Does not kumulirut. The general clearance – 0,37 ml/min., at the same time renal clearance - about 0,19 ml/min. It is removed by kidneys and with bile generally in not changed look, in insignificant degree - in the form of a metabolite: kidneys (by glomerular filtering and active canalicular secretion) – 26% in the form of a kandesartan and 7% - in the form of an inactive metabolite, with bile – 56% and 10%, respectively. After a single dose inside during 72 h more than 90% of a dose are removed.
At elderly patients (65 years are more senior) Cmax and the area under a curve "concentration time" (AUC) increase by 50% and 80%, respectively, in comparison with young patients. However the anti-hypertensive effect and frequency of emergence of side effects at use of drug do not depend on age of patients.
Patients with easy and average degree of renal failures have Cmax and AUC increase by 50% and 70%, respectively, whereas T1/2 of drug does not change in comparison with patients with normal function of kidneys.
At patients with heavy renal failures of Cmax and AUC increase by 50% and 110%, respectively, and T1/2 of drug increases twice.
At patients with easy and average degree of abnormal liver functions increase in AUC for 23% was observed.

Indications to use:

Arterial hypertension.
Chronic heart failure and disturbance of systolic function of a left ventricle (decrease in fraction of emission of a left ventricle less than 40%) as additional therapy to inhibitors of an angiotensin-converting enzyme (APF) or at intolerance of APF inhibitors.

Route of administration and doses:

Inside, regardless of meal, once a day.
Arterial hypertension
The recommended initial and maintenance dose makes 8 mg once a day. Patients who need further decrease in the ABP are recommended to increase a dose to 16 mg once a day. The maximum daily dose of medicine makes 32 mg once a day.
The maximum anti-hypertensive effect occurs in 4 weeks after an initiation of treatment.
If therapy by drug Angiakand does not lead to decrease in the ABP to the optimum target objective, it is recommended to add thiazide diuretic to therapy.
It is not required from patients of advanced age of correction of an initial dose.
From patients with an easy or moderate renal failure (KK more than 30 ml/min.) does not need change of an initial dose of drug.
Patients with a heavy renal failure (KK less than 30 ml/min.) and patients with an abnormal liver function of easy and average degree: the recommended initial dose – 4 mg once a day (use of drug of a kandesartan in other form of release is possible).
Chronic heart failure
The recommended initial dose makes 4 mg once a day (possibly use of drug of a kandesartan in other form of release).
Increase in a dose to 32 mg or to the most tolerable dose is carried out once a day by its doubling with an interval not less than 2 weeks.

Patients of advanced age and patients with a renal failure and/or a liver do not need change of an initial dose of drug.
Angiakand it is possible to apply together with other drugs used at therapy of chronic heart failure, for example, by APF inhibitors, beta adrenoblockers, diuretics and cardiac glycosides.

Features of use:

To and during treatment control of the ABP, function of kidneys (creatinine in a blood plasma), contents of potassium, lithium in blood serum (is necessary at the combined use of medicines).
Arterial hypotension
At patients with chronic heart failure against the background of therapy by drug Angiakand can develop arterial hypotension. As well as at use of other drugs influencing RAAS, reduction of OTsK as it is observed at the patients receiving high doses of diuretics can be the cause of development of arterial hypotension in patients with arterial hypertension. Therefore at the beginning of therapy it is necessary to be careful and, if necessary, to carry out correction of a hypovolemia.
Renal artery stenosis
With a bilateral renal artery stenosis or a stenosis of an artery of the only kidney the drugs exerting impact on RAAS, in particular APF inhibitors can cause increase in concentration of urea and creatinine in blood serum in patients. Similar effects can be expected at appointment of antagonists of receptors of angiotensin II.
Renal transplantation
Data on use of a kandesartan for the patients who recently transferred renal transplantation no.
Renal failure
Against the background of therapy by drug Angiakand, as well as at use of other means, the oppressing RAAS, for some patients renal failures can be noted.
At drug use Angiakand at patients with arterial hypertension and the expressed renal failure is recommended to control periodically the content of potassium and creatinine in blood serum. Clinical experience of use of a kandesartan for patients with a heavy renal failure or an end-stage of a renal failure (KK less than 15 ml/min.) is limited.
At patients with chronic heart failure it is necessary to control periodically function of kidneys, especially at patients at the age of 75 years and is more senior, and also at patients with a renal failure. At increase in a dose of drug Angiakand is also recommended to control the content of potassium and creatinine in a blood plasma.
Combined use with APF inhibitors at chronic heart failure
At drug use Angiakand in a combination with APF inhibitors can increase risk of development of side effects, especially renal failures and hyperpotassemias. In these cases careful observation and control of laboratory indicators is necessary.
General anesthesia and surgery
At the patients receiving antagonists of receptors of angiotensin II during the general anesthesia and at surgical interventions arterial hypotension as a result of blockade of RAAS can develop. Very seldom cases of the heavy arterial hypotension demanding intravenous administration of liquid and/or vazopressor can be noted.
Stenosis of the aortal and mitral valve (hypertrophic subaortic stenosis)
At drug use Angiakand, as well as other vazodilatator, patients should be careful with a hypertrophic subaortic stenosis or hemodynamically significant stenosis of the aortal and/or mitral valve.
Primary hyper aldosteronism
Patients with primary hyper aldosteronism usually rezistentna to therapy by the hypotensive drugs influencing activity of RAAS. In this regard Angiakand is not recommended to use drug at such patients.
Hyperpotassemia
Clinical experience of use of other drugs influencing RAAS shows that simultaneous use of a kandesartan with the kaliysberegayushchy diuretics, drugs of potassium or substitutes of salt containing potassium or other drugs which can increase the content of potassium in blood (for example, heparin) can lead to development of a hyperpotassemia in patients with arterial hypertension.
The general
Patients who have a vascular tone and function of kidneys preferential depend on activity of RAAS (for example, patients with heavy chronic heart failure or diseases of kidneys, including a renal artery stenosis), are especially sensitive to the drugs operating on RAAS. Use of similar means is followed at these patients with sharp arterial hypotension, an azotemia, oliguria less often – an acute renal failure. The possibility of development of the listed effects cannot be excluded also at use of antagonists of receptors of angiotensin II. Sharp decrease in the ABP at patients with coronary heart disease or cerebrovascular diseases of ischemic genesis, at use of any antihypertensives, can lead to development of a myocardial infarction or stroke.
Influence on ability to manage vehicles, mechanisms.
During treatment there can be dizziness, weakness therefore it is necessary to be careful at control of vehicles and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Arterial hypertension
The most often found side effects (> 1/100, <1/10):
From the central nervous system: dizziness, weakness, headache;
From a musculoskeletal system, connecting fabric: dorsodynia;
Others: respiratory infections;
Laboratory indicators: decrease in hemoglobin, a giperkreatininemiya, increase in concentration of urea in blood, a hyperpotassemia, a hyponatremia, increase in activity of alaninaminotranspherase (ALT).
Chronic heart failure
The most often found side effects (> 1/100, <1/10):
From cardiovascular system: the expressed decrease in the ABP;
From an urinary system: renal failure;
Laboratory changes: a giperkreatininemiya, increase in concentration of urea in blood, a hyperpotassemia.
During post-marketing use of a kandesartan it was reported about the following side effects (frequency – less than 1/10 000):
From bodies of a hemopoiesis: leukopenia, neutropenia and agranulocytosis;
Laboratory indicators: hyperpotassemia, hyponatremia;
From the central nervous system: dizziness, weakness, headache;
From the alimentary system: nausea;
From a liver and biliary tract: increase in activity of "hepatic" transaminases, abnormal liver function or hepatitis;
Allergic reactions: Quincke's disease, skin rash, itch, small tortoiseshell;
From a musculoskeletal system, connecting fabric: dorsodynia, arthralgia, mialgiya;
From an urinary system: a renal failure, including an acute renal failure at predisposed patients.
From respiratory system: cough.

Interaction with other medicines:

At the combined use of a kandesartan with a hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinylestradiol/levonorgestrel), glibenclamide, nifedipine and enalapril of clinically significant interactions it is not revealed.
At simultaneous use of drugs of lithium with APF inhibitors it was reported about reversible increase in concentration of lithium in blood serum and development of toxic reactions. Side reactions can meet also at use of antagonists of receptors of angiotensin II in this connection, it is recommended to control lithium level in blood serum at the combined use of these drugs.
At simultaneous use of antagonists of receptors of angiotensin II and non-steroidal anti-inflammatory drugs (NPVP), including the selection inhibitors of cyclooxygenase-2 (TsOG-2) and non-selective NPVP, for example, acetylsalicylic acid, more than 3 g/days, can decrease hypotensive action of a kandesartan. As well as in a case with APF inhibitors, simultaneous use of antagonists of receptors of angiotensin II and NPVP increases risk of depression of function of kidneys, up to development of a renal failure that leads to a hyperpotassemia at patients with a renal failure. This combination has to be applied with care, especially at patients of advanced age. All patients have to receive enough liquid. It is necessary to control function of kidneys at the beginning of therapy and further.
The medicines influencing RAAS can increase concentration of urea and creatinine in blood at patients with a bilateral stenosis of renal arteries or a stenosis of an artery of the only kidney.
Diuretics and other antihypertensives increase risk of development of arterial hypotension.
Kaliysberegayushchy diuretics, potassium drugs, the salt substitutes containing potassium, and other drugs which can increase the content of potassium in blood serum (for example, heparin) increase risk of development of a hyperpotassemia.
Kandesartan is metabolized in a liver in insignificant degree (CYP2C9 isoenzyme). The conducted researches on interaction did not reveal influence of a kandesartan on isoenzymes of CYP2C9 and CYP3A4. Action on other isoenzymes of system of P450 cytochrome is not studied.

Contraindications:

- hypersensitivity to a kandesartan or other components of drug;
- deficit of lactase, lactose intolerance, glyukozo-galaktozny malabsorption;
- pregnancy;
- lactation period;
- primary hyper aldosteronism (resistance to therapy);
- heavy abnormal liver functions and/or cholestasia;
- age up to 18 years.

With care:
Heavy renal failure (the clearance of creatinine (CC) less than 30 ml/min.), a bilateral stenosis of renal arteries, a renal artery stenosis of the only kidney, after renal transplantation in the anamnesis, hemodynamically significant stenosis of the aortal and mitral valve, cerebrovascular diseases, coronary heart disease, a hypertrophic subaortic stenosis, decrease in the volume of the circulating blood (VCB), a hyperpotassemia.

Use at pregnancy and a lactation:
In researches on animals injury of kidneys to the embryonal and neonatal periods at use of a kandesartan is revealed. It is supposed that the mechanism of damage is caused by pharmacological impact of drug on the renin-angiotensin-aldosteronovuyu system (RAAS).
At a human embryo the system of blood supply of a kidney which depends on development of RAAS begins to form in the second trimester of pregnancy. Thus, the risk for a fruit increases at use of a kandesartan in the second and third trimesters of pregnancy. The drugs having direct effect on RAAS can cause disturbances of fetation or have negative effect on the newborn, up to a lethal outcome, at use of drug in the second and third trimesters of pregnancy.
Angiakand it is not necessary to apply during pregnancy. If pregnancy is revealed during treatment by drug, therapy has to be stopped as soon as possible.
It is unknown whether it is allocated кандесартан in breast milk. Due to the possible undesirable action on babies, Angiakand it is not necessary to apply during feeding by a breast.

Overdose:

Symptoms: the expressed decrease in the ABP, dizziness, tachycardia.
Treatment: symptomatic to lay the patient on a back, to raise the lower extremities higher than the level of the head, if necessary - increase in the volume of the circulating blood (VCB) by infusion of 0,9% of solution of sodium of chloride, use of sympathomimetics. The hemodialysis is inefficient.

Storage conditions:

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

Issue conditions:

According to the recipe

Packaging:

Tablets of 8 mg, 16 mg and 32 mg.
On 7, 10, 20, 28 or 30 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished.
On 1, 2, 3, 4, 8 blister strip packagings on 7 tablets or on 1, 2, 3, 4, 5, 6 blister strip packagings on 10 tablets, or on 1, 2, 3 blister strip packagings on 20 tablets, or on 1, 2 blister strip packagings on 28 tablets, or on 1, 2 blister strip packagings on 30 tablets together with the application instruction place in a pack from a cardboard.