Кандекор®

General characteristics. Structure:

Acting veshchestvo:4,0 with mg, tsileksetit 8,0 mg, 16,0 mg or 32,0 mg of a kandesartan.

Excipients: lactoses monohydrate, starch corn, hypro rod, macrogoal 8000, karmelloza of calcium, magnesium stearate.

For a dosage of 8 mg, 16 mg, 32 mg: dye ferrous oxide red, E 172.

Anti-hypertensive drug.

Pharmacological properties:

Pharmacodynamics. Angiotensin II – the main enzyme the system renin-angiotensin-aldosteronovoy (SRAA) which is taking part in a pathogeny of the arterial hypertension (AH), heart failure and other cardiovascular diseases.

Kandesartan is the selection antagonist of receptors of angiotensin II, a subtype 1 (AT1-receptors). Does not show properties of an agonist (does not influence 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 influence a condition of the ion channels participating in regulation of activity 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. Reception of a kandesartan inside provides dozozavisimy, smooth decrease in the ABP due to reduction of the general peripheric vascular resistance (GPVR) without reflex increase in the heart rate (HR). There are no data on development of the expressed arterial hypotension after reception of the first dose or about development of a syndrome of "cancellation" after the therapy termination.

The beginning of hypotensive action after reception of the first dose of drug usually develops during 2 h, effect duration – 24 h. Against the background of the continuing therapy kandesartany in the fixed dose the maximum decrease in the ABP usually is reached within 4 weeks and remains throughout all treatment.

Addition of thiazide diuretic of a hydrochlorothiazide to a kandesartan strengthens its anti-hypertensive effect. The age and a sex of the patient do not influence efficiency of drug. Increases a renal blood stream and does not change or raises a glomerular filtration rate whereas the renal vascular resistance and filtrational fraction decrease.

Kandesartan renders less expressed anti-hypertensive effect at patients of negroid race (population with preferential low activity of a renin in a blood plasma).

There are no data on influence of a kandesartan on progressing of a diabetic nephropathy. At patients with arterial hypertension and a diabetes mellitus 2 types кандесартан do not exert a negative impact on concentration of glucose in blood and a lipidic profile.

Heart failure. Therapy kandesartany reduces rate of mortality and frequency of hospitalization at patients with the chronic heart failure (CHF) regardless of age, sex and the accompanying therapy, leads to reduction of functional class HSN on NYHA classification.

Kandesartan is effective at the patients accepting at the same time beta adrenoblockers in combination with APF inhibitors; at the same time its efficiency does not depend on an APF inhibitor dose. At patients with HSN and reduced systolic function of a left ventricle (the fraction of emission of a left ventricle (FELV) less than 40%) кандесартан OPSS and pressure of jamming in pulmonary capillaries reduces.

Pharmacokinetics. Absorption and distribution. Absolute bioavailability of a kandesartan makes about 40% after intake. Relative bioavailability makes about 34%.

The maximum concentration (Cmax) in blood serum is reached in 3 – 4 hours after intake.

Concentration in a blood plasma increases linearly at increase in a dose in a therapeutic interval (to 32 mg).

Communication with proteins of a blood plasma high (more than 99%). The volume of distribution of a kandesartan makes 0,1 l/kg.

Metabolism and removal. It is slightly metabolized in a liver (20-30%) with the participation of CYP2C9 isoenzyme with formation of inactive derivative.
The elimination half-life (T1/2) of a kandesartan makes about 9 hours. Does not kumulirut. The general clearance - about 0,37 ml/min., at the same time renal clearance of drug - 0,19 ml/min. After intake of a 14C-mechenny kandesartan of a tsileksetil of 26% of a dose it was removed by kidneys in the form of a kandesartan and 7% - in the form of an inactive metabolite, at the same time 56% of a dose are removed through intestines with bile in the form of a kandesartan and 10% - in the form of an inactive metabolite. After a single dose during 72 h more than 90% of a dose are removed.

Special groups of patients. At elderly patients (65 years are more senior) Cmax and the area under a curve "concentration time" (AUC) of a kandesartan increase in comparison with patients of young age approximately by 50% and 80%, respectively. 

However reaction from the ABP and possible side effects at use of a kandesartan do not depend on age of patients.

At patients with an easy or moderate renal failure of Cmax and AUC of a kandesartan increase approximately by 50% and 70%, respectively, at this T1/2 does not change in comparison with patients with safe 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 an easy or moderate abnormal liver function increase in AUC of a kandesartan by 23% is noted.

Indications to use:

• Arterial hypertension.
• Chronic heart failure and disturbance of systolic function of a left ventricle (FVLZh of £40%) as additional therapy to APF inhibitors or at intolerance of APF inhibitors - a badge ≤

Route of administration and doses:

Inside, 1 time a day, regardless of meal.

• Arterial hypertension. The recommended initial and maintenance dose of the drug KANDEKOR® makes 8 mg 1 times/days. If necessary it is possible to increase a dose to 16 mg of 1 times/days. The maximum anti-hypertensive effect is reached within 4 weeks of therapy. The maximum daily dose - 32 mg of 1 times/days.

If against the background of the maximum daily dose adequate control of the ABP is not reached, it is recommended to add thiazide diuretic to therapy.

Patients with reduced OTsK: at patients with risk of development of arterial hypotension therapy it is recommended to begin 4 mg with an initial dose.

Patients with a renal failure: from patients with an easy or moderate renal failure (KK more than 30 ml/min. / 1,73 body surface area sq.m) does not need change of an initial dose of the drug KANDEKOR® (8 mg).

Clinical experience of use of drug for patients with heavy renal failures (KK less than 30 ml/min. / 1,73 body surface area sq.m) is limited; in this case it is necessary to consider the possibility of the beginning of therapy from a dose of 4 mg/days. 

Patients with an abnormal liver function: with an abnormal liver function easy and moderate severity dose adjustment of the drug KANDEKOR® is not required from patients.

Clinical experience of use of drug for patients with heavy abnormal liver functions and/or a cholestasia is absent (see the section of the Contraindication).

• Chronic heart failure. The recommended initial dose of the drug KANDEKOR® makes 4 mg of 1 times/days. Increase up to the maximum daily dose - 32 mg of 1 times/days or to the most tolerable dose is carried out by doubling of a dose with an interval not less than 2 weeks. Elderly patients: dose adjustment of the drug KANDEKOR® is not required.

Features of use:

Heavy renal failures (the clearance of creatinine (CC) less than 30 ml/min.), a hemodialysis, a bilateral stenosis of renal arteries or a stenosis of an artery of the only kidney, hemodynamically significant stenosis of the aortal and/or mitral valve, a hypertrophic subaortic stenosis (GOKMP), a state after transplantation of a kidney, cerebrovascular disturbances of ischemic genesis and the coronary heart disease (CHD), a hyperpotassemia, at patients with a reduced the volume of the circulating blood (VCB), carrying out the general anesthesia and surgical interventions (risk of development of arterial hypotension, owing to blockade of RAAS), primary hyper aldosteronism.

Pregnancy. The drug KANDEKOR® is contraindicated at pregnancy since it кандесартан makes direct impact on RAAS, can cause disturbances of fetation or exert a negative impact on the newborn, up to a lethal outcome. When diagnosing pregnancy the drug KANDEKOR® needs to be cancelled as soon as possible. When planning pregnancy it is necessary to transfer the patient to adequate alternative therapy.

Lactation period. It is unknown whether gets кандесартан into breast milk, but it is known that it gets into breast milk of the lactating rats. During treatment by the drug KANDEKOR® breastfeeding needs to be stopped. Newborns whose mothers accepted during pregnancy КАНДЕКОР® have to be under careful medical observation because of probability of development of arterial hypotension.

Influence of the drug KANDEKOR® on control of motor transport and work with difficult mechanisms it was not studied, but pharmakodinamichesky properties of drug indicate that similar influence is absent. It is necessary to be careful at control of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Classification of frequency of development of side effects of the World Health Organization (WHO):
very often   > 1/10
often             from> 1/100 to <1/10
infrequently         from> 1/1000 to <1/100
seldom             from> 1/10000 to <1/1000
very seldom  from <1/10000, including separate messages.

Side effects of a kandesartan are poorly expressed and have passing character. Frequency of side effects does not depend on a dose of drug and age of the patient.
From a nervous system: often – dizziness, a headache, weakness;

From respiratory system: often – respiratory infections, pharyngitis, rhinitis;

From cardiovascular system: often – the expressed decrease in the ABP;

From urinogenital system: often – a renal failure, including a renal failure at predisposed patients;

From system of a hemopoiesis and lymphatic system: very seldom - a leukopenia, a neutropenia, thrombocytopenia and an agranulocytosis;

From the alimentary system: very seldom – nausea;

From gepatobiliarny system: very seldom – increase in activity of "hepatic" transaminases, an abnormal liver function or hepatitis;

From a musculoskeletal system: very seldom - a dorsodynia, an arthralgia, a mialgiya;

Laboratory indicators: very seldom - a hyperpotassemia, a hyponatremia, increase in concentration of creatinine in blood, a hyperuricemia, insignificant decrease in hemoglobin.

Allergic reactions: very seldom - a Quincke's disease, skin rash, an itch, a small tortoiseshell;

Others: an aggravation of a course of gout, "inflows" of blood to face skin.

Interaction with other medicines:

Simultaneous use of a kandesartan with a hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinylestradiol/levonorgestrel), glibenclamide, nifedipine and enalapril is studied.

Kandesartan in insignificant degree is metabolized in a liver (by means of CYP2C9 isoenzyme). Influence on isoenzymes of CYP2C9 and CYP3A4 is not revealed; the effect concerning other isoenzymes of P450 cytochrome is unknown now.

Anti-hypertensive means exponentiate hypotensive effect of a kandesartan. Experience of use of other medicines operating on RAAS shows that simultaneous use of a kandesartan and kaliysberegayushchy diuretics, drugs of potassium, the substitutes of salt containing potassium or other means capable to increase the content of potassium in blood serum (for example, heparin), can lead to development of a hyperpotassemia.

At simultaneous use of drugs of lithium and APF inhibitors cases of tranzitorny increase in concentration of lithium in blood serum and development of toxic effects were noted. The similar effect is possible at simultaneous use of drugs of lithium and antagonists of receptors of angiotensin II that it demands periodic control of concentration of lithium 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 tsikloogsigenazy-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.

Contraindications:

• Hypersensitivity to a kandesartan or excipients of drug;
• Pregnancy and period of a lactation;
• Galactosemia, deficit of lactase, syndrome of glyukozo-galaktozny malabsorption;
• Age up to 18 years (efficiency and safety are not established);
• Heavy abnormal liver functions and/or cholestasia.

Overdose:

Simptomy:vyrazhenny decrease in the ABP, dizziness, tachycardia. The separate cases of overdose of a kandesartan (to 672 mg of a kandesartan of a tsileksetil) which ended with recovery of patients without serious consequences are described.

Treatment: to transfer the patient to situation "lying" on spin with raised head over heels; further it is necessary to hold the events directed to increase in OTsK (introduction of 0,9% of solution of sodium of chloride intravenously). Symptomatic therapy under control of the vital functions of an organism. The hemodialysis is inefficient.

Storage conditions:

At a temperature not over 30 ºС. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets on 4 mg, 8 mg, 16 mg, 32 mg. On 7, 14 or 15 tablets in the blister.
- the blister on 7 tablets: 2, 4, 8, 12 or 14 blisters together with the application instruction in a pack cardboard;
- the blister on 14 tablets: 1, 2, 4, 6 or 7 blisters together with the application instruction in a pack cardboard;
- the blister on 15 tablets: 2, 4 or 6 blisters together with the application instruction in a pack cardboard.