Valz of N

General characteristics. Structure:

Active agent: валсартан 80 mg + hydrochlorothiazide of 12,5 mg; валсартан 160 mg + hydrochlorothiazide of 12,5 mg or валсартан 160 mg + hydrochlorothiazide of 25 mg.
excipients: cellulose microcrystallic, lactoses monohydrate, croscarmellose sodium, K29-32 povidone, talc, magnesium stearate, silicon dioxide colloid;
film cover: Опадрай II 85G34642 Pink (polyvinyl alcohol, talc, titanium dioxide, a macrogoal 3350, lecithin, dye ferrous oxide red, dye ferrous oxide yellow, dye ferrous oxide black) - for tablets of 80 mg +12,5 mg; Опадрай II 85G25455 Red (polyvinyl alcohol, talc, a macrogoal 3350, titanium dioxide, dye ferrous oxide red, dye a sunset yellow, lecithin) - for tablets of 160 mg +12,5 mg, Opadray of II 85G23675 Orange (polyvinyl alcohol, talc, titanium dioxide, a macrogoal 3350, dye ferrous oxide yellow, lecithin, dye ferrous oxide red, dye ferrous oxide black) - for tablets of 160 mg +25 mg;

Description
For tablets of 80 mg +12,5 mg:
oval biconvex tablets, film coated pink color, with marking of "V" on the one hand and "N" on the other hand.
For tablets of 160 mg +12,5 mg:
oval biconvex tablets, film coated red-brown color, with marking of "V" on the one hand and "N" on the other hand.
For tablets of 160 mg +25 mg:
oval biconvex tablets, film coated orange color, with marking of "V" on the one hand and "N" on the other hand.

Pharmacological properties:

Pharmacodynamics. The combined drug possessing hypotensive action consisting of a blocker of receptors of angiotensin II and thiazide diuretic. Valsartan - a peripheral vazodilatator, has hypotensive and diuretic effect. The specific blocker of receptors of AT1 of angiotensin II, does not inhibit APF; does not influence the content of the general cholesterol, triglycerides, glucose and uric acid, does not enter interaction and does not block the receptors of other hormones or ion channels important for regulation of functions of cardiovascular system. The lowering of arterial pressure (ABP) which is not followed by pulse rate change is noted. A hydrochlorothiazide - thiazide diuretic of average force. Reduces a reabsorption of ions of sodium at the level of a cortical segment of a Henle's loop, without influencing its site passing in a kidney medulla that defines weaker diuretic effect in comparison with furosemide. Blocks a karboangidraza in proximal department of gyrose tubules, strengthens removal by kidneys of potassium ions (in distal tubules ions of sodium exchanges on potassium ions), hydrocarbonates and phosphates. Practically does not influence an acid-base state (ions of sodium are removed or together with chlorine ions, or with a hydrocarbonate therefore at an alkalosis removal of a hydrocarbonate amplifies, at acidosis - chlorine ions). Increases magnesium removal; detains in an organism calcium ions and urates. The diuretic effect develops in 1-2 h, reaches a maximum in 4 h, proceeds 10-12 h. Action decreases at reduction of a glomerular filtration rate and stops at its size less than 30 ml/min. Lowers the arterial pressure (AP) due to reduction of the volume of the circulating blood (VCB), change of reactivity of a vascular wall, decrease in pressor influence of endogenous catecholamines (adrenaline and noradrenaline) and strengthening of depressor influence on a ganglion.
The maximum hypotensive effect is observed in the first 2-4 weeks of treatment.

Pharmacokinetics. Valsartan
 After intake absorption - bystry, extent of absorption is variable. Bioavailability - 23%. Time of achievement of the maximum concentration (TCmax) - 2 h. At reception with food the area under a curve "concentration time" (AUC) decreases by 48% that is not followed by clinically significant reduction of therapeutic effect. Communication with proteins of a blood plasma - 94-97%. At achievement of an equilibrium state distribution volume - 17 l. Drug is metabolized by the fermental CYP2C9 system. Elimination half-life (T1/2) of-9 h. It is removed through intestines - 70%, kidneys - 30%, it is preferential in not changed look.
Hydrochlorothiazide
 After intake the hydrochlorothiazide is quickly soaked up. Bioavailability makes 60-80%. TCmax of-2-5 h. Communication with proteins of a blood plasma of 60-80%. Gets through a gematoplatsentarny barrier and into breast milk. T1/2 is 6-15 h. It is not metabolized by a liver. It is removed by kidneys: more than 95% of a dose in not changed look and about 4% — in the form of a hydrolyzate — 2-amino-4-chloro-m-benzenedisulfonamida.
Валсартан / hydrochlorothiazide
 At combined use with valsartany system bioavailability of a hydrochlorothiazide decreases approximately by 30%, the hydrochlorothiazide has no significant effect on kinetics of a valsartan. Noted interaction does not influence efficiency of the combined use.

Indications to use:

• Arterial hypertension (patients to whom the combination therapy is shown).

Route of administration and doses:

Inside, irrespective of meal time, washing down with enough liquid.
The drug doses given below Valz of N are specified in the ratio valsartan/a hydrochlorothiazide.
The recommended dose - on 1 tablet Valz of N once a day a dosage of 80/12,5 mg. At patients for whom the daily dose of 80/12,5 mg does not give desirable effect Valz of N to 160/12,5 mg is recommended to increase a daily dose, for those patients to whom further decrease the ABP a daily dose of drug Valz is shown to N makes 160/25 mg respectively.
Patients with a renal failure when KK makes more than 30 ml/min., and also from patients with poorly or moderately expressed abnormal liver functions in the absence of the phenomena of a cholestasia do not need correction of a dose of drug Valz N.

Features of use:

Before treatment carry out correction of maintenance of ions of sodium to blood and/or OTsK.
Regular control of contents in a blood plasma of potassium ions, glucose, uric acid, a lipidic profile and creatinine as thiazide diuretics can cause change of tolerance to glucose, and also increase in concentration of cholesterol, triglycerides and uric acid in blood serum is necessary.
Simultaneous use of salts of potassium, kaliysberegayushchy diuretics, kaliysoderzhashchy substitutes of edible salt or any other medicines which can cause increase in potassium concentration in blood (for example, heparin) demands observance of precautionary measures and, in particular, frequent definition of potassium concentration in blood.
Dose adjustment of insulin or peroral hypoglycemic drug can be required.
There are messages that thiazide diuretics can cause an aggravation of a system lupus erythematosus.
Such undesirable effects as a hypopotassemia or a hypomagnesiemia which, in turn, increase risk of development of arrhythmia at glikozidny intoxication can cause thiazide diuretics.
In case of approach of pregnancy during treatment drug should be cancelled.
Influence on ability to drive the car and/or other mechanisms.
During treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Dizziness, feeling of fatigue, diarrhea, abdominal pain, nausea, cough, rhinitis, pharyngitis, viral infections, decrease in an indicator of a hematocrit, hyperpotassemia, giperkreatininemiya, arthralgia, stethalgia, allergic reactions, Quincke's disease, itch, serum disease, vasculitis, skin rash, renal failure.
Are potentially possible: валсартан - hypostases, sleeplessness, an adynamy, decrease in a libido (less than 1%); a hydrochlorothiazide - disorder of water and electrolytic balance; often: urticaria, loss of appetite, nausea, vomiting, orthostatic hypotension, decrease in a potentiality; seldom: a photosensitization, a lock or diarrhea, unpleasant feelings in a stomach, an intra hepatic cholestasia, jaundice, arrhythmias, a headache, a depression, paresthesias, vision disorders, thrombocytopenia, sometimes with a purpura; very seldom: the necrotizing vasculitis, a toxic epidermal necrolysis (Lyell's disease), skin reactions reminding hard currency, an aggravation of skin manifestations of hard currency, pancreatitis, a leukopenia, an agranulocytosis, oppression of marrow, hemolitic anemia, a pneumonitis, a fluid lungs.

Interaction with other medicines:

Strengthening of anti-hypertensive effect at combined use with other anti-hypertensive means is possible (such as vazodilatator, beta adrenoblockers, etc.). Strengthens a neurotoxicity of salicylates, side effects of cardiac glycosides, cardiotoxic and neurotoxic effect of drugs of lithium, efficiency of kurarepodobny muscle relaxants.
Reduces quinidine removal, weakens action of hypoglycemic means for intake, Norepinephrinum, Epinephrinum and antigouty means.
Increases the frequency of allergic reactions to Allopyrinolum; reduces removal by kidneys of cytotoxic means (cyclophosphamide, a methotrexate) and leads to strengthening of their myelosuppressive action.
The medicines which are intensively contacting blood proteins (indirect anticoagulants, Clofibratum, non-steroidal anti-inflammatory drugs (NPVP)) strengthen diuretic effect.
The hypotensive effect is strengthened by barbiturates, fenotiazina, tricyclic antidepressants, ethanol.
At a concomitant use Methyldopums hemolysis development is possible; Colestyraminum reduces absorption.
The risk of development of a hypopotassemia increases at co-administration of saluretics, corticosteroids, adrenocorticotropic hormone (AKTG), Amphotericinum In, a karbenoksolona, penicillin G and derivatives of salicylic acid
 Increase in bioavailability of thiazide diuretic is observed at co-administration of holinoblokator (for example, atropine, Biperidinum) that, apparently, it is connected with decrease in a physical activity of digestive tract and delay of gastric emptying.
At combined use of thiazide diuretics with vitamin D or salts of calcium increase in concentration of calcium in blood serum is possible.
Co-administration of cyclosporine can lead to increase in concentration of uric acid in blood that increases risk of development of a hyperuricemia and also can provoke a gout attack.

Contraindications:

• Hypersensitivity to active components or excipients of drug;
• The abnormal liver functions connected with impassability of bilious ways (including biliary cirrhosis, a cholestasia);
• Anury;
• A chronic renal failure (the clearance of creatinine (CC) less than 30 ml/min.), including the patients who are on a hemodialysis;
• A hyponatremia, a hypopotassemia, a hypercalcemia, a hyperuricemia with clinical manifestations, refractory to adequate therapy;
• System Lupus Erythematosus (SLE);
• Age up to 18 years (safety and efficiency are not established);
• Pregnancy, lactation period.

With care: a renal artery stenosis (unilateral or bilateral), transplantation of a kidney (there are no data on safety at use of a valsartan for the patients who recently transferred transplantation of a kidney); the states which are followed by decrease in OTsK (including diarrhea, vomiting); a concomitant use with drugs of salts of potassium, kaliysberegayushchy diuretics, and also with medicines which can cause increase in potassium concentration in blood (for example, heparin); at a concomitant use with thiazide diuretics; with poorly or moderately expressed abnormal liver functions in the absence of the cholestasia phenomena.

Overdose:

Symptoms: a lowering of arterial pressure that can lead to a loss of consciousness and to a collapse.
Treatment: a gastric lavage, reception of enough absorbent carbon, in/in 0.9% chloride sodium solution.
Valsartan is not brought at dialysis in connection with active linkng with proteins of a blood plasma.
The hemodialysis is effective concerning a hydrochlorothiazide.

Storage conditions:

At a temperature not above 30 °C. To store in the place, unavailable to children! Period of validity 3 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated 80 mg +12,5 mg; 160 mg +12,5 mg; 160 mg +25 mg.
On 7, 10 or 14 tablets in the blister from PVC/PE/PVDH / Aluminum foil or strips the Aluminium foil / Aluminum foil.
For a dosage of 80 mg +12,5 mg: on 1, 2, 4 blister or a strip on 7 tablets; on 1,2, 3, 10 blisters or strips on 10 tablets; on 4 or 7 blisters or strips on 14 tablets together with the application instruction in a pack.
For dosages of 160 mg + 12,5 mg and 160 mg + 25 mg: on 1, 2, 4 blister or a strip on 7 tablets; on 1, 2, 3, 9 blisters or strips on 10 tablets; on 4 or 7 blisters or strips on 14 tablets together with the application instruction in a pack.
On 50 or 100 blisters or strips together with application instructions in a cardboard box (for hospitals).