Ванатекс

General characteristics. Structure:

Active agent - валсартан 80 mg, 160 mg

Excipients: lactoses monohydrate, sodium of a kroskarmelloz, silicon dioxide colloid anhydrous, magnesium stearate

Structure of a cover of Advantia Prime 171996BA01: a gipromelloza of 6 cP, a macrogoal 400, titanium E 171 dioxide, gland (III) oxide red E172 (for a dosage of 80 mg),

Structure of a cover of Advantia Prime 145010BA01: a gipromelloza of 6 cP, a macrogoal 400, titanium E 171 dioxide, gland (III) oxide red E172, gland (III) oxide yellow E172, gland (III) oxide black E172 (for a dosage of 160 mg).

Pharmacological properties:

Pharmacodynamics. Valsartan is an active, powerful and specific antagonist of receptors of angiotensin II (Ang II). It affects selectively a subtype of receptors of AT1 which is responsible for action of ANG II. The increased ANG levels II after blockade of a receptor of AT1 valsartany can stimulate not blocked receptor of AT2 which, most likely, neutralizes action of a receptor of AT1 in a blood plasma. Valsartan does not show activity of a partial agonist concerning a receptor of AT1 and has considerably bigger (about 20 000-fold) affinity to AT1 receptor, than to AT2 receptor. It is unknown whether contacts валсартан other receptors of hormones or ion channels which, as we know, play an important role in cardiovascular regulation, or blocks them. Valsartan does not inhibit APF (also known as a kinase of II) which turns Ang I into Ang II and bradikinin destroys. As there is no impact on APF and potentiations of bradikinin or a proteic matter, antagonists of ANG II can be hardly connected with cough.
AG. Purpose of a valsartan the patient with AG as a result leads to decrease in the ABP, without influencing at the same time ChSS.
At most of patients after reception of a single peroral dose anti-hypertensive activity is noted during 2 h, and the maximum decrease in the ABP is reached during 4–6 h. The hypotensive effect remains during 24 h after administration of drug. At repeated use of medicine the hypotensive effect generally remains during 2 weeks, and the maximum effect is reached during 4 weeks and remains during the long period. In combination with a hydrochlorothiazide essential additional decrease in the ABP is reached.
Bystry cancellation of a valsartan is not connected with "ricochet" AG or other undesirable clinical phenomena.
Recently postponed myocardial infarction. Results of a research showed efficiency of a valsartan, as well as captopril, in decrease in the general mortality after a myocardial infarction. Valsartan was also effective concerning decline in mortality from cardiovascular pathology, reduction of quantity of cases of hospitalization concerning heart failure and a repeated myocardial infarction. The profile of safety of a valsartan answered the course of a disease of the patients treated after the established myocardial infarction.
Heart failure. Patients who accepted валсартан showed considerable improvement on signs and symptoms of heart failure, including an asthma, fatigue, hypostasis and rattles, in comparison with those who accepted placebo. The patients with chronic heart failure accepting валсартан had the best quality of life from initial to a final indicator in comparison with patients who accepted placebo. The patients accepting валсартан had a fraction of emission much more, and the final diastolic diameter of a left ventricle significantly decreased from initial to a final indicator in comparison with patients who accepted placebo.

Pharmacokinetics. Absorption. After oral administration of Cmax of a valsartan in a blood plasma it is reached in 2–4 h. Average absolute bioavailability makes 23%. Food reduces influence of a valsartan (that is determined by average concentration in urine/AUC) approximately by 40%, and Cmax in a blood plasma — approximately for 50% though approximately in 8 h after reception concentration of a valsartan in a blood plasma is similar that in group of the patients eating food and in group of the patients accepting drug on an empty stomach. However such decrease in average concentration in urine is not followed by clinically significant decrease in therapeutic effect and therefore валсартан it is possible to accept either with food, or without it.
Distribution. The equilibrium volume of distribution of a valsartan in/in introductions makes later 17 l, indicating that it валсартан is not distributed intensively in fabrics. It strongly contacts proteins of a blood plasma (94–97%), generally albumine.
Biotransformation. Valsartan biotransformirutsya in full as only about 20% of a dose are recovered in the form of metabolites. Gidroksimetabolit it is revealed in a blood plasma in low concentration (less than 10% of average concentration of a valsartan in urine). This metabolite pharmacological is inactive.
Removal. Valsartan shows multiexponential kinetics of disintegration (T½α <1 h and T½β about 9 h). He is generally brought with a stake (about 83% of a dose) and urine (about 13% of a dose), is preferential in not changed look. Later in/in introductions the clearance of a valsartan makes about 2 l/h, and its renal clearance — 0,62 l/h (about 30% of the general clearance). T½ of a valsartan makes 6 h.
Patients with heart failure
Average time to Cmax and T½ of a valsartan at patients with heart failure is similar to that which was noted at healthy volunteers. Indicators of AUC and Cmax of a valsartan are almost proportional (are identical) at reception of the dose exceeding the range of therapeutic doses (from 40 to 160 mg 2 times a day). The average coefficient of cumulation makes about 1,7.
The clearance of a valsartan after oral administration makes about 4,5 l/h. The age does not influence clearance at patients with heart failure.
Special groups of patients
Patients of advanced age. A little increased system influence of a valsartan was noted at some patients of advanced age in comparison with persons of young age, however it had no clinical value.
Renal failure. As well as it was supposed, with substance which renal clearance makes only 30% of the general clearance of a blood plasma, correlation between a condition of function of kidneys and system exposure of a valsartan is noted. Therefore to patients with a renal failure (clearance of creatinine> of 10 ml/min.) selection of a dose is not required. For today there is no experience of safe use for patients with clearance of creatinine <10 ml/min. and the patients who are on dialysis therefore at such patients валсартан it is necessary to apply with care. Valsartan contacts proteins of a blood plasma and can be hardly brought by means of dialysis.
Liver failure. About 70% of the absorbed dose are removed with bile, generally in not changed look. Valsartan does not give in to biotransformation which would deserve attention. At patients with a slight and moderate liver failure exposure (determined by AUC values) the valsartana on average twice exceeds that in comparison with healthy volunteers. However no interrelation between concentration of a valsartan in a blood plasma and degree of hepatic dysfunction was noted. Did not study efficiency of a valsartan at patients with heavy hepatic dysfunction.

Indications to use:

AG. Treatment of AG at adults.
Postinfarction state. Treatment of clinically stable patients with symptomatic heart failure or asymptomatic systolic dysfunction of a left ventricle after recent (the 12th p-10 of days) a myocardial infarction.
Heart failure. Treatment of symptomatic heart failure when it is impossible to apply APF inhibitors, or as auxiliary therapy at use of APF inhibitors when it is impossible to apply blockers of β-adrenoceptors..........

Route of administration and doses:

Valsartan it is possible to accept irrespective of meal, washing down with water.
AG. The recommended initial dose of a valsartan makes 80 mg (1 tablet of Vanateks 80 mg or ½ tablets of Vanateks of 160 mg) 1 time a day. The anti-hypertensive effect is reached in the first 2 weeks, and the maximum effect is noted during 4 weeks.
At some patients whose ABP is insufficiently controlled the dose can be raised to 160 mg, a maximum — to 320 mg.
Valsartan it is possible to accept with other anti-hypertensive drugs.
Addition of diuretic means, such as hydrochlorothiazide, reduces the ABP at such patients even more.
Postinfarction state. Treatment of clinically stable patients can be begun, applying валсартан already in 12 h after a myocardial infarction. After an initial dose of 20 mg 2 times a day a dose of a valsartan should be raised to 40; 80 and 160 mg 2 times a day within the next several weeks. Ванатекс do not appoint for initial treatment. For achievement of smaller doses (20 mg) it is necessary to accept drug in other dosage form. The maximum dose makes 160 mg 2 times a day. It is recommended that the dose of 80 mg 2 times a day was reached in 2 weeks after an initiation of treatment, and the maximum dose — 160 mg 2 times a day — in 3 months taking into account portability of treatment by the patient. When developing symptomatic arterial hypotension or renal dysfunction it is necessary to consider a dose decline question.
Valsartan it is possible to apply at patients who accepted other medicines after the postponed myocardial infarction, for example a trombolitika, acetylsalicylic acid, blockers of β-adrenoceptors, statines and diuretics. The combination with APF inhibitors is not recommended. Assessment of a condition of patients after the postponed myocardial infarction always has to include a research of function of kidneys.
Heart failure. The recommended initial dose of a valsartan makes 40 mg 2 times a day. It is necessary to raise a dose to 80 and 160 mg 2 times a day bucketed not less than 2 weeks, considering portability of drug the patient. It is necessary to consider the possibility of a dose decline of the accompanying diuretics. The maximum daily dose which was appointed made 320 mg and was divided into several receptions.
Valsartan it is possible to accept with other medicines for treatment of heart failure. However the triple combination of APF inhibitor, a blocker of β-adrenoceptors and a valsartana is not recommended. Assessment of a condition of patients with heart failure always has to include a research of function of kidneys.
Additional information of rather special groups of patients
Patients of advanced age. Selection of a dose is not required for patients of advanced age.
Patients with a renal failure. Selection of a dose is not required for patients with clearance of creatinine> 10 ml/min.
Patients with a liver failure. For patients with a slight and moderate liver failure without cholestasia the dose of a valsartan should not exceed 80 mg. Valsartan is contraindicated to patients with a heavy liver failure and to patients with a cholestasia.

Features of use:

Hyperpotassemia
Simultaneous use with potassium additives, kaliysberegayushchy diuretics, the salt substitutes containing potassium or other means which can increase potassium levels (heparin, etc.) is not recommended. If necessary it is necessary to carry out control of content of potassium to blood.
Patients with deficit of sodium
Patients with the expressed deficit of sodium, for example at those who accept diuretics in high doses seldom in an initiation of treatment can have a symptomatic arterial hypotension. Before an initiation of treatment it is necessary to carry out correction of content of sodium in an organism, for example, by a diuretic dose decline.
Patients with a hypovolemia
The patients with a heavy hypovolemia accepting high doses of diuretics can seldom have a symptomatic arterial hypotension after the begun therapy valsartany. The hypovolemia needs to be corrected before an initiation of treatment valsartany, for example, by a diuretic dose decline.
Renal artery stenosis
At patients with a bilateral renal artery stenosis or a stenosis of one kidney safe use of a valsartan is not established.
Short-term reception of a valsartan with the renovascular hypertensia which arose owing to a unilateral renal artery stenosis did not cause in patients any essential changes in a renal hemodynamics, creatinine level in a blood plasma or an urea nitrogen. However other means influencing a renin-angiotenzinovuyu system can increase levels of urea of blood and creatinine in a blood plasma at patients with a unilateral renal artery stenosis therefore monitoring of function of kidneys is recommended if the patient accepts валсартан.
Transplantation of kidneys
There is no experience of safe use of a valsartan for the patients who recently transferred transplantation of kidneys for today.
Primary hyper aldosteronism
At patients with primary hyper aldosteronism it is not necessary to apply валсартан as their renin-angiotenzinovaya system is not activated.
Stenosis of aortal and mitral valves, subaortic hypertrophic stenosis
As well as in a case with other vazodilatator, it is necessary to be especially careful at treatment of patients with a stenosis of aortal or mitral valves or a hypertrophic subaortic stenosis.
Renal failure
Dose adjustment for patients with clearance of creatinine> 10 ml/min. is not required. For today there is no experience of safe use of a valsartan for patients with clearance of creatinine <10 ml/min. and the patients who are on dialysis therefore such patients валсартан should appoint with care.
Liver failure
Patients with a slight and moderate liver failure without cholestasia валсартан should appoint with care.
Recently postponed myocardial infarction
The combination of captopril and valsartan does not show additional clinical benefits whereas the risk of side effects increases in comparison with that at treatment by appropriate means. Thus, the combined use of a valsartan with APF inhibitor is not recommended. It is necessary to be careful in an initiation of treatment of patients after the postponed myocardial infarction. Assessment of a condition of patients after the postponed myocardial infarction always has to include a research of function of kidneys.
Use of a valsartan for patients after the postponed myocardial infarction generally leads to some decrease in the ABP, but to stop treatment because of long symptomatic hypotension usually there is no need if to observe recommendations concerning a dosage.
Heart failure
Use for patients with heart failure of a triple combination of APF inhibitor, a blocker of β-adrenoceptors and a valsartana does not show any clinical advantages. This combination obviously increases risk of emergence of side effects and therefore it is not recommended.
In an initiation of treatment of patients it is necessary to be careful with heart failure. Assessment of patients with heart failure always has to include a research of function of kidneys.
Use of a valsartan for patients with heart failure generally leads to some decrease in the ABP, but to stop treatment because of long symptomatic hypotension usually there is no need if to follow the instruction concerning a dosage. At patients whose function of kidneys depends on activity a system renin-angiotenzinovoy (for example at patients with heavy congestive / an acute heart failure) treatment by APF inhibitors is connected with an oliguria and/or the progressing azotemia and, in some cases, with OPN and/or death. As валсартан is an antagonist of ANG II, it is impossible to exclude that use of a valsartan can be connected with a renal failure.
Excipients
Drug contains lactose (1 tablet of 80 mg contains 56,5 mg of lactose of monohydrate, 1 tablet of 160 mg contains 113 mg of lactose of monohydrate). Patients with rare hereditary intolerance have galactoses, a lactose intolerance or a sprue of glucose and a galactose it is not necessary to use this drug.
Use during pregnancy and feeding by a breast
Pregnancy. Use of antagonists of receptors of ANG II is not recommended during the entire period of pregnancy.
Before administration of drug of women of reproductive age it is necessary to inspect for an exception of possible pregnancy. If the woman wishes to become pregnant, it is necessary to stop use of drug and to replace it with any other anti-hypertensive medicine which has the established safety profile for use during pregnancy. If during treatment pregnancy is confirmed, it is necessary to pass as soon as possible (under observation of the doctor) to alternative therapeutic means which represent smaller risk for a fruit.
Feeding by a breast. Due to the lack of information use of a valsartan is not recommended during feeding by a breast.
Children. Valsartan do not recommend to apply at children (aged up to 18 years) due to the lack of data on its safety and efficiency.
Ability to influence speed of response at control of vehicles or work with other mechanisms. Did not conduct a research about influence on ability to manage vehicles. At control of vehicles or work with other mechanisms it is necessary to consider that there can sometimes be dizziness or the increased fatigue.

Side effects:

Are classified by frequency: very often (≥1/10); often (> 1/100, ≤1/10); sometimes (> 1/1000, ≤1/100); seldom (> 1/10 000, ≤1/1000); very seldom (<1/10 000), including single messages. Within each group side reactions are presented as reduction of their weight.
It is impossible to apply one of above-mentioned frequencies and therefore their frequency is designated to all adverse side reactions about which it was reported during the post-market and laboratory researches as it "is unknown".
AG
From blood and lymphatic system: it is unknown — decrease in level of hemoglobin, decrease in a hematocrit, a neutropenia, thrombocytopenia.
From immune system: it is unknown — hypersensitivity, including a serum disease.
From a metabolism: it is unknown — increase in level of potassium in a blood plasma, a hyponatremia.
From an acoustic organ and balance: infrequently — dizziness.
From vessels: it is unknown — a vasculitis.
From respiratory system: infrequently — cough.
From a digestive tract: infrequently — an abdominal pain.
From a liver and gall bladder: it is unknown — increase in indicators of function of a liver, including increase in level of bilirubin in a blood plasma.
From skin and hypodermic fabrics: it is unknown — a Quincke's edema (Quincke's disease), rash, an itch.
From a musculoskeletal system and connecting fabric: it is unknown — a mialgiya.
From kidneys and urinary tract: it is unknown — OPN and a renal failure, increase in level of creatinine in a blood plasma.
General disturbances: infrequently — increased fatigue.
The adverse side reactions which arose at patients after the postponed myocardial infarction and/or heart failure, provided below.
After the postponed myocardial infarction and/or heart failure
From blood and lymphatic system: it is unknown — thrombocytopenia.
From immune system: it is unknown — hypersensitivity, including a serum disease.
From a metabolism: infrequently — a hyperpotassemia; it is unknown — increase in level of potassium in a blood plasma, a hyponatremia.
From a nervous system: often — dizziness, postural dizziness; infrequently — a faint, a headache.
From an acoustic organ and balance: infrequently — dizziness.
From heart: infrequently — heart failure.
From vessels: often — arterial hypotension, orthostatic hypotension; it is unknown — a vasculitis.
From respiratory system: infrequently — cough.
From the alimentary system: infrequently — nausea, diarrhea.
From a liver and gall bladder: it is unknown — increase in activity of enzymes of a liver, increase in concentration of bilirubin in a blood plasma.
From skin and hypodermic fabrics: infrequently — a Quincke's edema (Quincke's disease); it is unknown — rash, an itch.
From a musculoskeletal system and connecting fabric: it is unknown — a mialgiya.
From kidneys and urinary tract: often — a renal failure and a renal failure; infrequently — OPN, increase in level of creatinine in a blood plasma; it is unknown — increase in an urea nitrogen in blood.
General disturbances: infrequently — an adynamy, increased fatigue.

Interaction with other medicines:

Simultaneous use is not recommended
Lithium
It was reported about reversible increase in concentration of lithium in a blood plasma and toxicity at the accompanying use of APF inhibitors. Due to the lack of experience of simultaneous use of a valsartan and lithium this combination is not recommended. If such combination is necessary, careful control of level of lithium in a blood plasma is recommended.
Kaliysberegayushchy diuretics, potassium additives, the salt substitutes containing potassium, and other substances which can increase potassium level
If drug which influences potassium level it is necessary to combine with valsartany, control of level of potassium in a blood plasma is recommended.
It is necessary to be careful at simultaneous use of NPVP, including the selection TsOG-2 inhibitors, acetylsalicylic acid (> 3 g/days) and non-selective NPVP.
At co-administration of antagonists of ANG II and NPVP easing of anti-hypertensive effect is possible. Besides, simultaneous use of antagonists of ANG II and NPVP can result in the increased risk of deterioration in function of kidneys and increase in level of potassium in a blood plasma. Thus, it is recommended to control function of kidneys in an initiation of treatment, and also to carry out the corresponding hydration of the patient.
Other types of interactions. During the research it is not established any clinically significant interactions of a valsartan with any of the following substances: Cimetidinum, warfarin, furosemide, digoxin, атенолол, indometacin, hydrochlorothiazide, амлодипин, Glibenclamidum.

Contraindications:

Hypersensitivity to active ingredient or any of excipients. Heavy liver failure, cirrhosis and cholestasia.

Overdose:

Symptoms. The overdose valsartany can lead to the expressed arterial hypotension that, in turn, can become the reason of oppression of consciousness, a circulator collapse (vascular insufficiency) and/or shock (coma).
Treatment. Therapeutic measures depend on time of the use of food, and also a look and weight of symptoms, blood circulation stabilization is extremely important.
At arterial hypotension the patient has to be in a prone position, at the same time it is necessary to carry out correction of OTsK. It is improbable that валсартан is removed by a hemodialysis.

Storage conditions:

In the dry place at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

On 14 tablets in a blister strip packaging from PVC / PCTFE Is scarlet/.
On 2 planimetric packagings together with the application instruction in the state and Russian languages put in a pack from a cardboard.