Вальсакор® ND160

General characteristics. Structure:

Tablets, film coated 1 table.
kernel  
active agents: валсартан 160 mg; hydrochlorothiazide of 25 mg;
excipients: MKTs; lactoses monohydrate; magnesium stearate; croscarmellose sodium; povidone; silicon dioxide colloid anhydrous  
the cover is film: gipromelloza; titanium dioxide (Е 171); macrogoal 4000, dye ferrous oxide yellow (E172); dye ferrous oxide red (E172)  

Description of a dosage form

Oval, biconvex tablets, film coated, light brown color.

Pharmacological properties:

Pharmacodynamics. The combined antihypertensive.

Valsartan. Is the selection antagonist of receptors of angiotensin II 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 counterbalances the effects connected with blockade 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 APF 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 are not potentiated therefore at reception of antagonists of receptors of angiotensin II development of dry cough is improbable. Valsartan does not enter interaction and does not block the receptors of other hormones or ion channels participating in regulation of function of cardiovascular system. At treatment of arterial hypertension валсартан the ABP reduces, without influencing ChSS.

After intake of a single dose of a valsartan the anti-hypertensive effect develops during 2 h, and the maximum decrease in the ABP is reached during 4–6 h. The anti-hypertensive effect of a valsartan remains during 24 h. At repeated purposes of a valsartan the maximum decrease in the ABP, regardless of a dose, is reached in 2–4 weeks and remains 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 a syndrome of "cancellation" (sharp raising of the ABP or other undesirable clinical effects).

Hydrochlorothiazide. Thiazide diuretic which diuretic effect is connected with disturbance of a reabsorption of ions of sodium, chlorine, potassium, magnesium, water in distal department of nephron; removal of calcium ions, uric acid detains. Possesses hypotensive action which is caused by expansion of arterioles, Practically does not exert impact on normal indicators of the ABP. The diuretic effect develops in 1–2 h after administration of drug inside, reaches a maximum in 4 h and remains during 6–12 h. Anti-hypertensive action comes in 3–4 days, but for achievement of optimum therapeutic effect 3–4 weeks can be required.

Pharmacokinetics. Valsartan

It 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%. Tmax is 2 h. At administration of drug inside, once in days, its accumulation is insignificant. Plasma concentration of a valsartan are identical at men and women.

Valsartan actively contacts serum proteins (94–97%), is preferential with a seralbumin. Equilibrium volume of distribution of drug small, about 17 l. Plasma clearance rather low (about 2 l/h) when comparing with a hepatic blood-groove (about 30 l/h). It is metabolized by means of CYP2C9 isoenzyme. T1/2 makes 9 h. It is removed preferential in not changed look through intestines (70%) and kidneys (30%).

At reception of a valsartan with food AUC decreases by 48%. Nevertheless, in 8 h after reception plasma concentration of the valsartan accepted on an empty stomach or with food are identical. Reduction of AUC is not followed by clinically significant decrease in therapeutic effect of a valsartan therefore drug can be used irrespective of meal.

Hydrochlorothiazide

After intake absorption of a hydrochlorothiazide makes 60–80%. Cmax of a hydrochlorothiazide in blood is reached in 2 h after intake. Linkng with proteins of a blood plasma — 40–70%.

The hydrochlorothiazide is not metabolized and quickly removed through kidneys (more than 95%). T1/2 makes 6–15 h.

Special groups of patients

Patients with a renal failure

Considering that the renal clearance makes only 30% of the 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 a blood plasma high, its removal at a hemodialysis is improbable.

Patients with an abnormal liver function

About 83% of a valsartan are removed through intestines, is 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. In this regard 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. Вальсакор® ND 160 is not recommended to patients with abnormal liver functions (see the section "Route of Administration and Doses").

Patients of advanced age

At some patients of advanced age a little bigger system influence of a valsartan in comparison with young volunteers is revealed; however it is not established whether have these distinctions clinical value. The system clearance of a hydrochlorothiazide decreases at elderly patients in comparison with young people.

Indications to use:

Arterial hypertension at 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® ND 160 can be combined with other anti-hypertensive means. Treatment needs to be begun with the minimum doses of drug.

The fixed combination — Valsakor® of ND 160 (160/25 mg) of 1 times a day is recommended to the patients who did not reach the target objective of the ABP against the background of monotherapy valsartany in a dose of 160 mg or a hydrochlorothiazide in a dose of 25 mg.

The maximum anti-hypertensive effect of the drug Valsakor® ND 160 (160/25 mg) develops during 2–4 weeks.

To patients with renal failures (clearance of creatinine> of 30 ml/min. (0,5 ml / c) are not required changes of doses of drug.

Вальсакор® ND 160 is not recommended to patients with abnormal liver functions. The maximum recommended daily dose of a valsartan — 80 mg is at patients with easy or moderate abnormal liver functions of not biliary origin — 1 tab./days of the drug Valsakor® N 80.

Dose adjustment is not required to patients of advanced age.

Features of use:

Patients with heavy chronic heart failure in a stage of a decompensation or other states which are followed by stimulation the system renin-angiotensin-aldosteronovoy (SRAA).

Use of the drug Valsakor® ND 160 for this group of patients usually is followed by more expressed decrease in the ABP, however at observance of recommendations about selection of doses treatment seldom demands cancellation because of arterial hypotension. Therapy by the drug Valsakor® ND 160 should be carried out with care. Owing to suppression of activity of RAAS at some patients development of a renal failure is possible. At heavy chronic heart failure development of an oliguria and/or the progressing azotemia up to an acute renal failure and/or death is possible (in rare instances). At patients with chronic heart failure regular control of function of kidneys is necessary, at co-administration of a combination of 3 classes of drugs — APF inhibitors, beta adrenoblockers and antagonists of receptors of angiotensin II (AT1). Appointment in a combination with other HP appointed after the postponed myocardial infarction is possible: trombolitik, acetylsalicylic acid, beta adrenoblockers and statines.

Patients with a hyponatremia and/or reduced OTsK

At patients with the expressed hyponatremia and/or reduced OTsK, for example owing to reception of high doses of diuretics, in rare instances at the beginning of therapy by the drug Valsakor® ND 160 the expressed arterial hypotension can develop. Before an initiation of treatment it is recommended to correct disturbances of water and electrolytic balance, in particular, by reduction of doses of diuretics. At development of arterial hypotension with clinical manifestations 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. Therapy by the drug Valsakor® ND 160 can be continued only after stabilization of indicators of the ABP.

Renal artery stenosis

Safety of use of the drug Valsakor® ND 160 for patients with a bilateral or unilateral stenosis of renal arteries, and also a stenosis of an artery of the only kidney is not established (possibly increase in serumal concentration of urea and creatinine).

Renal failure

Change of doses of drug is not required from patients with renal failures (creatinine Cl> of 30 ml/min. (more than 0,5 ml / c)). It is recommended to control periodically the maintenance of potassium ions, concentration of creatinine and uric acid in blood serum. Experience of use of the drug Valsakor® ND 160 for patients with recently postponed transplantation of kidneys is absent.

Abnormal liver function

Patients with an abnormal liver function are recommended to accept no more than 80 mg/days of a valsartan (see the section "Route of Administration and Doses").

Primary hyper aldosteronism

Вальсакор® ND 160 is not recommended to patients with primary hyper aldosteronism.

HARD CURRENCY

There are messages on an aggravation of a current of hard currency at use of thiazide diuretics.

Other metabolic disturbances

Thiazide diuretics can change tolerance to glucose and increase serumal concentration of cholesterol, triglycerides and uric acid.

Вальсакор® ND 160 contains lactose therefore patients should not appoint drug with hereditary intolerance of a galactose, deficit of lactase of Lapp or a syndrome of the broken glucose galactose absorption.

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

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; 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 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 a 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 necrotizing vasculitis, a toxic epidermal necrolysis (Lyell's disease), volchanochnopodobny reactions, an aggravation of a current of hard currency.

Laboratory indicators: often — a hyperpotassemia, a hypopotassemia, a hyponatremia, a hypomagnesiemia, a hypercalcemia; seldom — anemia, including hemolitic, a leukopenia, an agranulocytosis, oppression of marrow, decrease in concentration of hemoglobin and a hematocrit, a neutropenia, thrombocytopenia (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 HP: 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), kaliysoderzhashchy nutritional supplements, the drugs increasing potassium level in blood serum (APF inhibitors, heparin, cyclosporine) can lead to a hyperpotassemia in this connection it is required to be careful.

The 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 II 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 HP 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, 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 of a class 1A (quinidine, hydroquinidine, Disopyramidum), antiarrhytmic means of the III class (Amiodaronum, дофетилид, ибутшид), соталол, some neuroleptics (thioridazine, Chlorpromazinum, levomepromazinum, трифлуооперазин, циамемазин, Sulpiridum, сультоприд, амисульприд, тиаприд, Pimozidum, a haloperidol, Droperidolum), other drugs (bepridit, цизаприд, difemanit, erythromycin in / century, галофантрин, 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 in blood is recommended.

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 — dose adjustment 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 decreases and myelosuppressive action is exponentiated.

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 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.

NPVP (including TsOG-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.

The concomitant use with calcium drugs, vitamin D can lead to increase in maintenance of calcium ions in blood that can distort results of a research of function of epithelial bodies.

Contraindications:

Hypersensitivity to a valsartan, a hydrochlorothiazide, derivatives of sulfonamide and other components of drug;

pregnancy and period of a lactation;

the expressed abnormal liver functions, biliary cirrhosis and impassability of bilious ways (cholestasia) and easy or moderate abnormal liver functions of not biliary origin (for this dose of drug);

anury, the expressed renal failures (creatinine Cl less than 30 ml/min. (0,5 ml / c));

hemodialysis;

hypopotassemia, hyponatremia, hypercalcemia or 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 syndrome of the broken absorption of a glucose/galactose.

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 (creatinine Cl> of 30 ml/min. (0,5 ml / c), 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 by OTsK and/or a hyponatremia (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.

Use at pregnancy and feeding by a breast

Valsartan. 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 during this period 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 drug was used in the II-III trimesters of pregnancy, then it is necessary to carry out ultrasonography 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® ND 160 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® ND 160 in the period of a lactation it is necessary to cancel breastfeeding.

Overdose:

Valsartan 

Symptoms: the expressed decrease in the ABP which can lead to dizziness, a collapse and/or shock from the death.

Treatment: symptomatic, is recommended induction of vomiting and a gastric lavage, 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 an 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, 160+25 mg. On 7 or 14 pieces in the blister. 4, 8, or 14 blisters (according to 7 tab.) or on 2, 4, or 7 blisters (according to 14 tab.) in cardboard in a pack.