Вальсакор® H160

General characteristics. Structure:

Active agent: валсартан 160 mg
Excipients: lactoses monohydrate, cellulose microcrystallic, povidone, croscarmellose sodium, silicon dioxide colloid, anhydrous, magnesium stearate.

COVER:

Tablet, film coated, 160 mg: a gipromelloza, titanium dioxide (E171), dye ferrous oxide yellow (E172), dye ferrous oxide red (E172), a macrogoal - 4000.

Description
Tablets of 160 mg: oval, biconvex tablets with risky on one party, film coated brownish-yellow color.

Pharmacological properties:

Valsartan is the selection antagonist of receptors of angiotensin II (AT1 type) for intake, the nonprotein nature.

Has selective antagonistic effect on AT1 subtype receptors. Increase in plasma concentration of angiotensin II which can stimulate not blocked AT2 subtype receptors that presumably regulates effects of AT1 receptors is a consequence of blockade of AT1 receptors. Valsartan has no agonistic activity concerning AT1 receptors. Its affinity to AT1 subtype receptors approximately in 20000 times more, than to AT2 subtype receptors.

Valsartan does not inhibit the angiotensin-converting enzyme (ACE) known also under the name of a kininaza II which turns angiotensin I into angiotensin II and bradikinin destroys. Due to the lack of influence on APF, effects of bradikinin and substance P therefore at reception of antagonists of angiotensin II development of dry cough is improbable are not exponentiated. Valsartan does not enter interaction and does not block the receptors of other hormones or ion channels participating in regulation of functions of cardiovascular system.

At treatment of arterial hypertension валсартан reduces arterial pressure, without influencing the heart rate (HR). After intake of a single dose of drug the anti-hypertensive effect develops within 2 hours, and the maximum lowering of arterial pressure (ABP) is reached within 4-6 hours. The anti-hypertensive effect of drug remains within 24 hours after its reception. At repeated purposes of a valsartan the maximum decrease in the ABP, regardless of doses, is reached in 2-4 weeks and supported at the reached level during long therapy. The combination with a hydrochlorothiazide allows to reach significant additional decrease in the ABP.

The sudden termination of reception of a valsartan is not followed by sharp raising of the ABP or other undesirable clinical effects.

Tolerance to an exercise stress

At impact assessment of the valsartan (appointed in addition to standard therapy of heart failure) on portability of an exercise stress at patients with chronic heart failure of the II-IV functional classes on classification of NYHA and with the fraction of emission of a left ventricle (FELV) <40% increase in time of an exercise stress in comparison with initial indicators was noted.

There is no syndrome of "cancellation" at the sudden termination of reception.

Pharmacokinetics. Valsartan is quickly soaked up after intake, however extent of absorption varies over a wide range. The average size of absolute bioavailability of a valsartan makes 23%. Time necessary for achievement of the maximum concentration (TCmax), - 2 hours. After regular reception the maximum decrease in the ABP occurs in 4 weeks. At administration of drug once in days its accumulation is insignificant. Plasma concentration of a valsartan are identical at men and women. Valsartan actively contacts proteins of serum (94-97%), is preferential with a seralbumin. Equilibrium volume of distribution of drug small, about 17 liters. Plasma clearance rather low (about 2 l/hour) when comparing with a hepatic blood-groove (about 30 l/hour). It is metabolized by the fermental CYP2C9 system. The elimination half-life makes 9 hours. The quantity of the valsartan which is removed through intestines makes 70% of the dose which is soaked up after intake.

With urine 30% are removed, it is preferential in not changed look. At reception of a valsartan with food the area under a curve "concentration time" (AUC) decreases by 48%. Nevertheless, in 8 hours after administration of drug plasma concentration of the valsartan accepted on an empty stomach and with food are identical. Reduction of AUC is not followed by clinically significant reduction of therapeutic effect of a valsartan therefore drug can be used both to, and after food.

Special groups of patients

Patients with a renal failure

Considering that the renal clearance makes only 30% of size of the general clearance, correction of doses of drug is not required from patients with a renal failure. Since, extent of linkng of a valsartan with proteins of plasma high, its removal at a hemodialysis is improbable.

Patients with an abnormal liver function

About 70% of the soaked-up dose of a valsartan are removed with bile, preferential, in not changed look. Valsartan is not exposed to essential biotransformation therefore his systemic action does not correlate with degree of an abnormal liver function. Therefore change of a dose of a valsartan is not required from patients with a liver failure of not biliary origin and in the absence of a cholestasia. At patients with biliary cirrhosis or obstruction of biliary tract of AUC of a valsartan increases approximately twice.

Indications to use:

• Arterial hypertension.
• Chronic heart failure (the II-IV functional class on NYHA classification) as a part of complex therapy (against the background of standard therapy) and at the patients who are not receiving APF inhibitors.

Route of administration and doses:

Mvnutr,    irrespective of    meal,  frequency rate  of reception  -   1   time  a  day. Вальсакор® the N 160 can combine with other anti-hypertensive means. Treatment

it is necessary to begin with the minimum doses of drug.

The fixed combination is recommended to the patients who did not reach the target objective of the ABP against the background of monotherapy (a valsartan in a dose of 160 mg or a hydrochlorothiazide in a dose of 12,5 mg)

- Вальсакор® N 160 (160/12,5 mg) 1 time a day.

The maximum anti-hypertensive effect of the drug Valsakor® N 160 (160/12,5 mg) develops within 2-4 weeks. If necessary (level of the diastolic ABP is higher than 100 mm Hg against the background of monotherapy valsartany) for achievement of more expressed effect possibly increase (not earlier than, in 4-8 weeks) drug doses to 160/25 mg (use of the drug Valsakor® ND 160 is possible) 1 time a day.

Patients with renal failures (KK more than 30 ml/min. (0,5 ml/sec.)) do not need change of doses of drug. Вальсакор® the N  160 is not recommended to patients  with   abnormal liver functions.

Most recommended daily dose of a valsartan at patients with easy or moderate abnormal liver functions of not biliary origin - 80 mg (1 tablet in days of the drug Valsakor® N 80). It is not required to patients of advanced age of dose adjustment.

Features of use:

Heart failure
Use for patients with heart failure usually is followed by decrease in the ABP, however at observance of recommendations about selection of doses treatment seldom demands cancellation because of arterial hypotension. Therapy by Valsakor at patients with heart failure should be begun carefully. Owing to activity suppression system renin-angiotensin-aldosteronovoy at some patients change of function of kidneys is possible. At heavy heart failure development of an oliguria and/or the progressing azotemia up to (seldom) acute renal failure and/or death is possible. At patients with heart failure constant control of function of kidneys at co-administration of a combination of three classes of drugs - APF inhibitors, beta adrenoblockers and antagonists of receptors of AT1 angiotensin II is necessary.

Appointment in a combination with other medicines appointed after the postponed myocardial infarction is possible: trombolitik, acetylsalicylic acid, beta adrenoblockers and statines.

Patients with deficit of sodium and/or liquid At patients with the expressed deficit in an organism of sodium and/or the reduced the volume of the circulating blood (VCB), for example, owing to reception of high doses of diuretyak, in rare instances at the beginning of therapy valsartany the expressed arterial hypotension can develop. Before an initiation of treatment a valsakor it is recommended to recover the content of electrolytes and liquid in an organism, in particular, by reduction of doses of diuretics.

At development of arterial hypotension with clinical manifestations: the patient needs to be laid on a back and if necessary intravenously to enter 0,9% chloride sodium solution. Therapy by Valsakor can be continued only after stabilization of indicators of the ABP.

Renal artery stenosis
At patients with a bilateral or unilateral stenosis of renal arteries it is necessary to control constantly the content of creatinine and an urea nitrogen in serum.

Renal failure
Change of doses of drug is not required from patients with renal failures. Due to the lack of data on use of drug at a heavy renal failure (clearance of creatinine / c) in such cases drug it is recommended to appoint less than 10 ml/min. or 0,167 ml with care.

Abnormal liver function
Change of doses of drug is not required from patients with an abnormal liver function. Valsakor is brought preferential with bile. At patients with obstructive diseases of biliary tract reduction of clearance of Valsakor therefore in such cases it is necessary to appoint drug with care was observed.

Special information on excipients
Valsakor contains lactose therefore drug is contraindicated to patients with deficit of lactase, a galactosemia or a syndrome of the broken glucose galactose absorption.

Influence on ability to drive the car and other mechanisms: patients need to be careful when driving and other mechanisms requiring special attention.

Side effects:

From the central and peripheral nervous system: often - a headache, dizziness, including postural, вертиго; not often - sleeplessness; sometimes - a syncope (at use after the postponed myocardial infarction).

From respiratory system, bodies of a thorax and a mediastinum: often - cough, infections of upper parts of respiratory tracts, pharyngitis, rhinitis, sinusitis.

From cardiovascular system: often - the expressed decrease in the ABP and orthostatic hypotension; sometimes (at use after the postponed myocardial infarction) - heart failure.

From digestive tract: often - nausea, diarrhea, an abdominal pain.

From skin and hypodermic cellulose: seldom - skin rash.

From muscles, a skeleton and connecting fabric: often - a dorsodynia, a mialgiya, an arthralgia.

From urinogenital system: not often - decrease in a libido; very seldom - a renal failure.

Allergic reactions: very seldom - a Quincke's disease, skin rash, a skin itch, hypersensitivity reactions, including a serum disease and a vasculitis.

From laboratory parameters: seldom - decrease in concentration of hemoglobin and a hematocrit, a neutropenia, thrombocytopenia, a giperkreatininemiya, a hyperbilirubinemia, increase in activity of "hepatic" transaminases, increase in a serumal urea nitrogen; often - a hyperpotassemia.

Others: often - the general weakness; not often - hypostases, an adynamy, increased fatigue.

Interaction with other medicines:

Clinically significant pharmacokinetic interactions with other medicines are noted. The drugs tested in clinical trials included Cimetidinum, warfarin, digoxin, атенолол, indometacin, a hydrochlorothiazide, амлодипин and Glibenclamidum.

As валсартан is not exposed to essential metabolism, it is not necessary to expect also the significant medicinal interactions connected with induction or inhibition of system of P450 cytochrome. The concomitant use of kaliysberegayushchy diuretics (Spironolactonum, Triamterenum, amiloride), kaliysoderzhashchy nutritional supplements can lead to a hyperpotassemia, in communication; what it is required to be careful with. At joint reception with diuretics strengthening of hypotensive effect is possible.

Contraindications:

• Hypersensitivity to a valsartan or to other components of drug.
• Pregnancy and period of a lactation.
• Age up to 18 years (efficiency and safety of a valsartan at children is not proved).
• A lactose intolerance, a galactosemia or a syndrome of the broken absorption of a glucose/galactose.

With care: arterial hypotension, a liver failure against the background of impassability of bilious ways, a renal failure (the clearance of creatinine (CC) less than 10 ml/min.), including the patients who are on a hemodialysis, a hyponatremia, a diet with sodium consumption restriction, the bilateral stenosis of renal arteries or a stenosis of an artery of the only kidney, states which are followed by decrease in the volume of the circulating blood (VCB) (including diarrhea, vomiting).

Use at pregnancy and in the period of a lactation
There are no data on use of a valsartan at pregnancy. Renal perfusion of a fruit which depends on development a system renin-angiotenzinovoy begins to function in the third trimester of pregnancy. The risk for a fruit increases at reception of a valsartan in the second and third trimesters. At pregnancy establishment therapy valsartany has to be immediately stopped. There are no data on allocation of a valsartan in maternal milk. Therefore it is necessary to resolve an issue of the feeding termination by a breast or therapy cancellation valsartany taking into account its importance for mother.

Overdose:

Symptoms: the overdoses of a valsartan given about effects are absent. Despite the lack of enough data, the main expected drug overdose manifestation - the expressed decrease in the ABP which can lead to a collapse and/or shock.

Treatment: symptomatic, is recommended to cause vomiting and to wash out a stomach. At development of arterial hypotension intravenously enter 0,9% chloride sodium solution. The hemodialysis is inefficient.

Storage conditions:

To store at a temperature not above 30 °C. To store in the place, unavailable to children. Period of validity 2 years. Not to apply after expiry date.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 160 mg + 12,5 mg.

On 7 or 14 tablets place in the blister. On 4, 8, or 14 blisters (the blister on 7 tablets) either 2, 4, or 7 blisters (the blister on 14 tablets) in a pack cardboard together with the application instruction.