Вальсакор® H80

General characteristics. Structure:

Tablets, film coated 1 table.
active agents:  валсартан 80 mg; hydrochlorothiazide of 12,5 mg
excipients: MKTs; lactoses monohydrate; magnesium stearate; croscarmellose sodium; povidone; silicon dioxide colloid anhydrous  
the cover is film: gipromelloza; titanium dioxide (E171); macrogoal 4000; dye ferrous oxide red (E172); dye ferrous oxide yellow (E172)

Description
Oval, biconvex tablets, film coated pink 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 (patients to whom the combination therapy is shown).

Route of administration and doses:

Inside,      irrespective of      meal,   frequency rate   of reception   -   1   time   a   day.
Вальсакор® the N 80 can combine with other anti-hypertensive means.
To the patients who did not reach the target objective of the ABP against the background of monotherapy (valsartan or hydrochlorothiazide), the fixed combination of doses - Valsakor® of N 80 (80/12,5 mg) is recommended  once a day. At insufficiency of hypotensive effect increase in a dose of drug to maximum daily - 2 tablets Valsakor® N 80 or 1 the tablet Valsakor® ND 160 of 1 times a day is possible.
The maximum anti-hypertensive effect of the drug Valsakor® N 80 (80/12,5 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.
Most recommended daily dose of the drug Valsakor® N 80 at patients with easy or moderate abnormal liver functions of an iyebiliarny origin - 1 tablet a day (80/12,5 mg).
It is not required to patients of advanced age of dose adjustment.

Features of use:

With care! a concomitant use of drugs of potassium, the kaliysberegayushchy diuretics, kaliysoderzhashchy substitutes of edible salt and other means capable to increase potassium level in blood (for example, heparin), chronic heart failure the IV functional class on NYHA classification, a renal failure (KK more than 30 ml/min. (0,5 ml/sec.)), moderate abnormal liver functions, a bilateral or unilateral stenosis of renal arteries or a stenosis of an artery of the only kidney, a state after transplantation of kidneys, the states which are followed by decrease in the volume of the circulating blood (VCB) and/or ions of sodium (including diarrhea, vomiting), primary hyper aldosteronism, a stenosis of aortal and mitral valves, a hypertrophic subaortic stenosis (GOKMP), the system lupus erythematosus (SLE), hypersensitivity to other antagonists of receptors of angiotensin II, allergic reactions and bronchial asthma.

Side effects:

Classification of frequency of development of side effects of the world organization
 health care (WHO):
very often  > 1/10
often              from> 1/100 to <1/10
sometimes           from> 1/1000 to <1/100
seldom             from> 1/10000 to <1/1000
very seldom from <1/10000, including separate messages.
The undesirable phenomena had in general slight and passing character.
From the central and peripheral nervous system:  often - the general weakness;
sometimes - increased fatigue, an adynamy, dizziness, including postural, вертиго, sleeplessness; seldom - a headache, a depression, paresthesias, neuralgia; very much
 seldom - a syncope (at use after the postponed myocardial infarction).
From respiratory system: often - a nasopharyngitis; sometimes - infections of upper parts of respiratory tracts, rhinitis, sinusitis, cough; very seldom - a respiratory distress syndrome with a pneumonitis and a fluid lungs.
From cardiovascular system: sometimes - a stethalgia; often - the expressed decrease in the ABP and orthostatic hypotension; very seldom - arrhythmias; potentially perhaps - hypostases peripheral.
From a digestive tract: often - diarrhea; sometimes - nausea, dyspepsia,  an abdominal pain; seldom - a gastroenteritis,  a loss of appetite, a lock;  very seldom - pancreatitis, an intra hepatic cholestasia, jaundice.
From integuments and a hypodermic fatty tissue: seldom - skin rash, photosensitivity; very seldom - an alopecia.
From a musculoskeletal system:  sometimes -   a dorsodynia, extremities, stretching and ruptures of sheaves and muscles or muscular sinews, arthritis, an arthralgia; seldom - a mialgiya, muscular weakness, myotonia.

From urinogenital system: sometimes ~ decrease libido, impotence (less than 1%), infections    of an urinary   path,    viral    infections,    increase   in frequency of an urination; very seldom - a renal failure.
 From  sense bodys:  sometimes -  a vision disorder; seldom -   a sonitus, conjunctivitis.
Allergic reactions: very seldom - a Quincke's disease, a small tortoiseshell, skin rash, an itch, hypersensitivity reactions, including a serum disease and a yekrotiziruyushchy vasculitis, a toxic epidsrmalny necrolysis (Lyell's disease), volchanochnopodobny reactions, an aggravation of a current of hard currency.
Laboratory  indicators:  often  - a hyperpotassemia,  a hypopotassemia,  a hyponatremia, a giiomagniyemiya, a hypercalcemia; seldom - anemia, including hemolitic, a leukopenia, an agranulocytosis,  oppression    of marrow,  decrease  in concentration  of hemoglobin and a hematocrit, a neutropenia, a trombotsitopeyiya (sometimes with a purpura),  a giperkreatininemiya, a hyperbilirubinemia, increase in activity of "hepatic" transaminases, increase in concentration of a serumal urea nitrogen.
Others: seldom - the increased sweating; very seldom - bleeding (nasal).

Interaction with other medicines:

Valsartan
 Clinically significant pharmacokinetic interactions with medicinal
 means: Cimetidinum, warfarin, digoxin, атенолол, indometacin, a hydrochlorothiazide, амлодипин and Glibenclamidum it is noted.
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), kaliysoderleashchy nutritional supplements, the drugs increasing potassium level in blood serum (APF inhibitors, heparin, cyclosporine) can bring to AI hyper potassium in this connection it is required to be careful.
Concomitant use with other anti-hypertensive means, including diuretics
- leads to strengthening of hypotensive effect.
At a concomitant use of drugs of lithium and antagonists of receptors of angiotensin I
- cases of reversible increase in maintenance of ions of lithium in blood serum and increase in its toxicity are registered. Regular control of maintenance of ions of lithium in blood is recommended.
Hydrochlorothiazide
 With thiazide diuretics such medicines as ethanol, barbiturates and drugs, can exponentiate risk of development of orthostatic hypotension.
Hypoglycemic means (for intake and insulin) - dose adjustment of hypoglycemic means can be required.
Other antihypertensives - the additive effect.
Cholinolytics (for example, atropine, Biperidinum) - increase bioavailability of thiazide diuretics.
Colestyraminum and колестипол - in the presence of anion exchange pitches absorption of a hydrochlorothiazide decreases.
Corticosteroids, adrenocorticotropic hormone (AKTG), purgatives, Amphotericinum In, карбеноксолон, a benzatina benzylpenicillin, salicylic acid and salicylates - decrease in content of electrolytes, in particular a hypopotassemia is possible, it is regularly recommended to control the maintenance of potassium ions in blood.
Antiarrhytmic means classes of IA (quinidine, hydroquinidine, Disopyramidum), antiarrhytmic means of Iiiklassa (Amiodaronum, дофетилид, ибутилид), соталол, some neuroleptics (thioridazine, hlorpromaziya, levomepromazinum, трифтороперазин, циамемазин, Sulpiridum, сультоприд, амисулъприд, тиаприд, Pimozidum,
haloperidol, Droperidolum), other drugs (bepridit, цизаприд, difemanit, erythromycin in/in, galofantriya, кетансерин, мизоластин, pentamidine, спарфлоксацин, терфенадин, Vincaminum in/in) - risk of development of arrhythmia like "pirouette" against the background of a possible hypopotassemia and a hypomagnesiemia. Control of maintenance of potassium ions is recommended in
 blood.
Cardiac glycosides - risk of development of arrhythmia against the background of a hypopotassemia and a hypomagnesiemia.
Beta adrenoblockers and diazoxide - strengthening of hypoglycemic effect of these
 means.
Uricosuric means (пробенецид, Sulfinpyrazonum, Allopyrinolum) - increase in concentration of uric acid in blood, and also increase in frequency of development of hypersensitivity reactions to Allopyrinolum is possible; if necessary - correction
doses of uricosuric means.
Pressor amines (for example, Epinephrinum, Norepinephrinum) - decrease in effect of pressor amines is possible.
Amantadin - increases risk of side effects of an amantadin.
Cytotoxic means (for example, cyclophosphamide, a methotrexate) - removal of cytotoxic means and potentiation of myelosuppressive action decreases.
Muscle relaxants of not depolarizing action type (for example, tubocurarine) - strengthening of effect of muscle relaxants.
Cyclosporine - increases risk of a hyperuricemia and subagrosimilar complications.
Tetracyclines (except doxycycline) - risk of increase in concentration of urea in
 to blood serum.
Methyldopum - cases of hemolitic anemia are described.
Lithium - diuretics reduce renal clearance of lithium and increase risk of development of toxic effect of lithium; control of content of lithium in blood is recommended.
Non-steroidal anti-inflammatory drugs (IPVP) (including cyclooxygenase-2 inhibitors; for example, salicylic acid, derivatives of indolacetic acid) ~ can reduce diuretic, natriuretic and hypotensive effect of diuretics, development of an acute renal failure is possible. To lead a concomitant use with calcium drugs, Dmozhet vitamin to increase in maintenance of calcium ions in blood that can distort results of a research of function of epithelial bodies.

Influence on ability to drive the car and other mechanisms

Patients need to be careful at management of transport and work with other difficult mechanisms requiring special attention since development of dizziness or weakness against the background of arterial hypotension is possible.

Contraindications:

Hypersensitivity to a valsartan, gidrokhlorot to azide, derivatives of sulfonamide and to other components of drug; pregnancy and period of a lactation; the expressed abnormal liver functions, biliary cirrhosis and impassability of bilious ways (cholestasia); an anury, the expressed renal failures (the clearance of creatinine (CC) less than 30 ml/min. (0,5 ml/sec.)); hemodialysis; a hypopotassemia, a hyponatremia, a hypercalcemia or a hyperuricemia with clinical manifestations, refractory to adequate therapy; age up to 18 years (efficiency and safety of a valsartan at children is not established); intolerance of a galactose, deficit of lactase of Lapp or a syndrome of the broken absorption of a glucose/galactose.

Pregnancy and feeding by a breast

Use of antagonists of receptors of angiotensin II is not recommended during the I trimester of pregnancy. Drug is contraindicated in the II-III trimesters of pregnancy as use in the II-III trimesters of pregnancy can cause fetotoksichesky effects (depression of function of kidneys, an oligoamnios, delay of ossification of bones of a skull of a fruit) and neonatal toxic effects (a renal failure, arterial hypotension, a hyperpotassemia). If nevertheless used drug in the II-III trimesters of pregnancy, then it is necessary to conduct ultrasound examination of kidneys and bones of a skull of a fruit.
When planning pregnancy it is recommended to transfer the patient to alternative anti-hypertensive therapy taking into account a safety profile.
At pregnancy confirmation the drug Valsakor® N 80 needs to be cancelled as soon as possible. There are no data on allocation of a valsartan in breast milk. However it is known what валсартан gets into milk of the lactating rats. The hydrochlorothiazide is allocated with breast milk. Therefore in need of therapy by the drug Valsakor® N 80 in the period of a lactation it is necessary to cancel breastfeeding.

Overdose:

Valsarta

Symptoms: the expressed decrease in the ABP which can lead to dizziness, a collapse and/or shock from the death.
Treatment:  symptomatic,  is recommended  to cause  vomiting   and   to wash out  a stomach, purpose of absorbent carbon. At development of arterial hypotension it is necessary: to give to the patient horizontal position with the raised legs, to fill OTsK and to carry out    correction    of disturbances     of water and electrolytic    balance.    The hemodialysis is inefficient.

Hydrochlorothiazide
Symptoms: the most frequent symptoms are a consequence of deficit of electrolytes (a hypopotassemia, a hypochloraemia, a hyponatremia) and dehydrations owing to excessive
 diuresis: nausea, drowsiness, arrhythmia, spasm of muscles. At a concomitant use of cardiac glycosides the hypopotassemia can aggravate the course of arrhythmias.
Treatment: symptomatic.

Storage conditions:

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

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 80 mg + 12,5 mg.
On 7 or 14 tablets 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.