Ko-Valsartan

General characteristics. Structure:

Active ingredients: 160 mg of a valsartan, 12,5 mg of Hydrochlorthiazidum.

Vveshchestva: cellulose microcrystallic, кросповидон, silicon dioxide colloid anhydrous, magnesium stearate.

Structure of a cover: Опадрай II 85G25455 red (polyvinyl alcohol, talc, macrogoal, titanium dioxide (Е 171), dye ferrous oxide red (Е 172), dye yellow "sunset" (Е 110), lecithin).

Complex hypotensive drug, включающй diuretic component.

Pharmacological properties:

Pharmacodynamics. Active ingredients of drug are валсартан and Hydrochlorthiazidum. Valsartan is the selection blocker of receptors of angiotensin II (the SCONCE of II), active at intake. It selectively affects AT1 subtype receptors which are responsible for the known effects of angiotensin II. Valsartan has no agonistic activity concerning AT1 of receptors. Its affinity to AT1 subtype receptors approximately in 20000 times more, than to AT2 subtype receptors.

Pharmacodynamics. Valsartan does not inhibit the angiotensin-converting enzyme (ACE) known also as kininaz of II who 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 receptors 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 the arterial pressure (AP), without influencing heart rate.

After intake of a single dose of drug the anti-hypertensive effect develops within 2 hours, and the maximum decrease in the ABP is reached within 4-6 hours. After administration of drug anti-hypertensive action remains more than 24 h. At repeated purposes of drug the maximum decrease in the ABP, regardless of the accepted dose, is usually reached within 2-4 weeks and supported at the reached level during long therapy. The combination with Hydrochlorthiazidum reduces arterial pressure more effectively.

Hydrochlorthiazidum – thiazide diuretic. A point of application of effect of thiazide diuretics is the cortical department of distal renal tubules where the receptors having high sensitivity to effect of diuretics and where there is an oppression of transport of ions of Na and C1 are located. The mechanism of action of tiazid is connected with oppression of the pump Na+ Sl-that, obviously, occurs due to the competition for places of transport of S1-. Thereof excretion of ions of sodium and chlorine increases approximately equally. As a result of diuretic action reduction of volume of the circulating plasma is observed owing to what activity of a renin, secretion of Aldosteronum, removal of potassium with urine and, therefore, decrease in potassium concentration in serum increases. The interrelation between a renin and Aldosteronum is mediated by angiotensin II therefore appointment of the antagonist of receptors of angiotensin II reduces the potassium losses connected using thiazide diuretic.

Indications to use:

Treatment of arterial hypertension at adult patients at whom it is not possible to reach adequate control of arterial pressure at monotherapy valsartany or Hydrochlorthiazidum.

Route of administration and doses:

Pill is taken inside, without chewing, washing down with enough water, irrespective of meal.

The recommended Ko-Valsartana's dose – 1 tablet a day. Titration of a dose of separate components is recommended. In each case it is necessary to control titration with increase in a dose of individual components for the purpose of decrease in risk of development of hypotension and other side effects.

In the presence of the clinical bases it is possible to consider direct transition from monotherapy to the combined medicine with the fixed dose at patients whose arterial pressure is insufficiently controlled by monotherapy valsartany or Hydrochlorthiazidum, at respect for the recommended sequence of titration of doses of individual components.

If necessary for control of arterial pressure the dosage can be increased after 1-2 weeks of treatment to the maximum daily dose of 320 mg of a valsartan and 25 mg of Hydrochlorthiazidum.

The anti-hypertensive effect is reached within 2 weeks. At most of patients the maximum anti-hypertensive effect is reached within 4 weeks. However, for some patients, 4-8 weeks of treatment can be required. It has to be considered at titration of a dose.

Special groups of patients. Patients with a renal failure. Dose adjustment is not required from patients with a slight and moderate renal failure (the glomerular filtration rate (GFR) of ≥30 ml/min. / 1,73 sq.m) dose adjustment is not required. Drug is contraindicated to patients with a heavy renal failure (SKF <30 ml/min. / 1,73 to sq.m) and an anury as it contains Hydrochlorthiazidum. Simultaneous use of a valsartan with aliskireny is contraindicated at patients with a moderate / heavy renal failure (SKF <60 ml/min. / 1,73 to sq.m) (see the section "Contraindications").

Patients with a diabetes mellitus. Simultaneous use of a valsartan with aliskireny is contraindicated at patients with a diabetes mellitus (see the section "Contraindications").

Patients with abnormal liver functions. At patients with easy and moderate abnormal liver functions without cholestasia the dose of a valsartan should not exceed 80 mg. Change of a dose of Hydrochlorthiazidum is not required from patients with easy and moderate abnormal liver functions. Drug is contraindicated to patients with heavy abnormal liver functions, biliary cirrhosis and to patients with a cholestasia as it contains валсартан.

Elderly patients. Patients of advanced age do not need change of a dose of Ko-Valsartana.

Features of use:

Admission of the next administration of drug. If you forgot to accept drug, then it is not necessary to compensate the admission by reception of a double dose, just accept a usual dose of drug.

Termination of administration of drug. If you stop Ko-Valsartana's reception, then your arterial pressure can increase again. It is necessary to continue administration of drug even if you well feel. If you intend to stop administration of drug, then surely consult with the doctor.

At emergence of additional questions on use of this drug, consult to your attending physician or the druggist.

Changes of balance of electrolytes. Co-administration of a valsartan with potassium drugs, the salt substitutes containing potassium, kaliysberegayushchy diuretics or other drugs which can increase potassium concentration in blood serum is not recommended (heparin, etc.). It is recommended to control potassium concentration in blood serum.

It was reported about cases of development of a hypopotassemia during treatment by thiazide diuretics. It is recommended to control potassium level in blood serum.

Treatment by thiazide diuretics is often connected with emergence of a hyponatremia and gipokhloremichesky alkalosis. Tiazida, including Hydrochlorthiazidum, strengthen removal of magnesium with urine that can lead to development of a hypomagnesiemia. Tiazida reduce calcium excretion with urine that can lead to development of a hypercalcemia. Periodic control of concentration of electrolytes in blood serum is recommended.

Patients with deficit in an organism of sodium and/or the reduced the volume of the circulating blood (VCB). Patients with the expressed deficit in an organism of sodium and/or reduced OTsK, for example, of the diuretics receiving high doses, in rare instances in an initiation of treatment Co-Valsartan can have a symptomatic hypotension. Before an initiation of treatment it is necessary to carry out correction of contents in an organism of sodium and/or OTsK.

Patients with the heavy heart failure and other states which are followed by activation system renin-angiotensin-aldosteronovoy. At patients with heavy heart failure at whom function of kidneys depends on activity of RAAS treatment by APF inhibitors can become the reason of an oliguria and/or the progressing azotemia, and in rare instances of an acute renal failure and/or death. Assessment of a condition of patients with heart failure or a postinfarction state always has to include assessment of function of kidneys. Use of drug for patients with heavy heart failure was not studied. Therefore it is impossible to exclude that RAAS inhibition Co-Valsartan can also lead to deterioration in function of kidneys. In this regard it is not recommended to apply Ko-Valsartan at this group of patients.

Stenosis of renal. Ko-Valsartan should not apply to treatment of arterial hypertension at patients with a unilateral or bilateral stenosis of renal arteries or a stenosis of an artery of the only kidney since increase in concentration of urea in blood and concentration of creatinine in blood serum at these patients is possible.

Primary giperaljdosteronizm. Ko-Valsartana's appointment as their renin-angiotenzinovaya the system is not active is not recommended to patients with primary hyper aldosteronism.

Stenosis of the aortal or mitral valve, subaortic hypertrophic stenosis. As well as for other vazodilatator, at Ko-Valsartana's use to patients with an aortal or mitral stenosis or a hypertrophic subaortic stenosis, it is necessary to observe extra care.

Renal failure. From patients with a renal failure (clearance of creatinine> of 30 ml/min.) drug dose adjustment is not required. Periodic control of serumal potassium concentration, creatinine and uric acid at the patients with a renal failure accepting Ko-Valsartan is recommended.

Simultaneous use of Ko-Valsartana with aliskireny is contraindicated at patients with a renal failure (SKF <60 ml/min. / 1,73 to sq.m) (see sections of "Contraindication" and "Route of Administration and Doses").

Transplantation of kidneys. Now there are no data on safety of use of Ko-Valsartana for the patients who recently underwent an operation on renal transplantation.

Abnormal liver function. At patients with an easy and moderate abnormal liver function without Ko-Valsartan's cholestasia it is necessary to apply with care. Patients should appoint thiazide diuretics with care with abnormal liver functions or the progressing form of diseases of a liver as the insignificant hypovolemia and an electrolytic imbalance can provoke development of a hepatic coma.

Quincke's disease in the anamnesis. It was reported about cases of development of a Quincke's disease, including the hypostasis of a throat and glottis leading to obstruction of respiratory tracts and/or a face edema, lips, a throat and/or language at the patients accepting валсартан. Some of these patients had in the anamnesis a case of development of a Quincke's disease after reception of other drugs, including APF inhibitors. In case of development of a Quincke's disease patients should stop immediately Ko-Valsartana's reception, repeated appointment of drug is not allowed.

System lupus erythematosus. It was reported that thiazide diuretics cause an aggravation or activate manifestations of a system lupus erythematosus.

Other metabolic disturbances. Thiazide diuretics, including Hydrochlorthiazidum, can cause change of tolerance to glucose and increase in concentration of cholesterol, triglycerides and uric acid in serum. Dose adjustment of insulin or peroral antihyperglycemic means can be required by patients with diabetes.

Tiazida can reduce removal of calcium ions with urine and cause temporary and slight increase of serumal concentration of calcium. The expressed hypercalcemia can be a symptom of the hidden hyperparathyreosis. It is recommended to stop treatment by thiazide diuretics before test according to function of epithelial bodies.

Photosensitivity. Reception of thiazide diuretics can provoke development of reactions of photosensitivity. In case of development of reaction of photosensitivity it is recommended to stop treatment by Co-Valsartan. In need of repeated reception of diuretics it is recommended to protect open sites of skin from sunshine and Uv-radiation.

Pregnancy. Treatment of the SCONCE of II (including Co-Valsartan) cannot be begun during pregnancy. Unless it is impossible to make replacement of BRAII by other alternative therapy, the patients planning pregnancy have to be transferred to anti-hypertensive therapy by medicines at which the safety profile for pregnant women is well studied.

At pregnancy approach reception of the SCONCE of II has to be stopped immediately, and if necessary other anti-hypertensive therapy is appointed.

General disturbances. It is necessary to be careful at patients with hypersensitivity to other antagonists of receptors of angiotensin II. Reactions of hypersensitivity to Hydrochlorthiazidum are most widespread among patients with an allergy or asthma.

Acute closed-angle glaucoma. Hydrochlorthiazidum, being sulfonamide derivatives, can cause idiosyncratic reaction in the form of an acute tranzitorny myopia and acute closed-angle glaucoma. Symptoms of these disturbances include unexpected decrease in visual acuity or eye pain which arise during from several hours to several weeks after the beginning of use of drug. In the absence of treatment acute closed-angle glaucoma can lead to sight loss.

At emergence of these symptoms administration of drug needs to be stopped. If intraocular pressure remains uncontrollable, urgent conservative or surgical treatment can be required. To risk factors of development of acute closed-angle glaucoma data on an allergy can be carried to sulfonamides or penicillin in the anamnesis.

Double blockade of RAAS. Hypotonia, a faint, a stroke, a hyperpotassemia and renal failures (including an acute renal failure) were noted at persons with hypersensitivity, especially - at a combination of the medicines influencing RAAS. In this regard double blockade of RAAS at co-administration of an aliskiren with APF or SCONCE II inhibitors is not recommended (including with valsartany).

Contraindicated simultaneous use of drug of Ko-Valsartan with aliskireny at patients with a diabetes mellitus or a moderate / heavy renal failure (SKF <60 ml/min. / 1,73м2).

In the presence at you one of the listed diseases or states before administration of drug surely consult with the doctor.

Use during pregnancy and feeding by a breast. Pregnancy. Ko-Valsartana's use is contraindicated at pregnancy.

Valsartan. Use of the SCONCE of II is not recommended in the first trimester of pregnancy and it is contraindicated in the second and third trimesters of pregnancy.

Epidemiological data showed the increased risk of teratogenic influence at use of APF inhibitors in the first trimester of pregnancy. The similar risk can exist also at reception of the SCONCE of II (including a valsartana). At the patients planning pregnancy, in case of need alternative anti-hypertensive treatment which has the established safety profile for use during pregnancy has to be appointed.

At pregnancy approach reception of the SCONCE of II (including Ko-Valsartana) has to be stopped immediately, and if necessary other anti-hypertensive therapy is appointed.

It is known that reception of the SCONCE of II in the second and third trimesters causes a fetotoksichnost (depression of function of kidneys, an oligoamnios, a delay of ossification of a skull) and neonatal toxicity (a renal failure, arterial hypotension, a hyperpotassemia).

If the woman accepted the SCONCE II in the second trimester pregnancies, then control of function of kidneys and a skull of a fruit is necessary for ultrasonography. Newborns whose mothers accepted the SCONCE of II have to be under careful medical observation in connection with possible arterial hypotension.

Hydrochlorthiazidum. Experience of use of Hydrochlorthiazidum during pregnancy, especially in the first trimester, is limited. The data obtained in tests for animals are insufficient. Hydrochlorthiazidum gets through a placental barrier. Proceeding from the mechanism of pharmacological action of Hydrochlorthiazidum at its use in the second and third trimesters of pregnancy disturbance of fetoplacental perfusion and development in a fruit or the newborn of jaundice, disturbance of electrolytic balance and thrombocytopenia is possible.

Feeding by a breast. The possibilities of purpose of a valsartan given relatively during feeding by a breast are absent. Hydrochlorthiazidum gets into breast milk. Therefore it is not recommended to apply Ko-Valsartan during breastfeeding. Patients should be transferred to alternative therapy by medicines with well studied safety profile when breastfeeding, especially if the child newborn or premature.

Influence on ability to drive the car and potentially dangerous mechanisms. Researches on impact assessment of drug of Ko-Valsartan on ability to drive the car and to work with mechanisms were not conducted. At control of vehicles or work with mechanisms it is necessary to consider possibility of dizziness or weakness.

Side effects:

Side effects for which possible communication using a valsartan in a combination with Hydrochlorthiazidum was recognized are listed below. Classification of frequency of development of side effects: very often (≥ 1/10); often (≥1/100, but <1/10); infrequently (≥1/1000, but <1/100); seldom (≥1/10000, but <1/1000), it is very rare (<1/10000).

At use of a combination of a valsartan and Hydrochlorthiazidum the following side effects are possible:

Disturbances from a metabolism and food: infrequently – dehydration.

Disturbances from a nervous system: infrequently – paresthesia; very seldom – dizziness; frequency is unknown – a syncope (at use after the postponed myocardial infarction).

Disturbances from an organ of sight: infrequently – a sight illegibility.

Disturbances from an acoustic organ and labyrinth disturbances: infrequently – a sonitus.

Disturbances from vessels: infrequently – hypotension.

Disturbances from respiratory system, bodies of a thorax and a mediastinum: infrequently – cough; frequency is unknown – not cardiogenic fluid lungs.

Disturbances from the digestive tract (DT): very seldom – diarrhea.

Disturbances from skeletal and muscular and connecting fabric: infrequently – a mialgiya; very seldom – an arthralgia.

Disturbances from kidneys and urinary tract: frequency is unknown – a renal failure.

The general frustration and disturbances in an injection site: infrequently – increased fatigue.

Influence on results of laboratory and tool researches: frequency is unknown – increase in concentration of uric acid, creatinine and bilirubin in serum, a hypopotassemia, a hyponatremia, increase in content in urea nitrogen blood, a neutropenia.

The undesirable phenomena which are earlier noted at use of each of components can take place at Ko-Valsartana's use even if they were not observed in clinical trials.

Valsartan. The following undesirable phenomena were noted at monotherapy valsartany, irrespective of relationship of cause and effect with this drug:

Disturbances from blood and lymphatic system: frequency is unknown – decrease in concentration of hemoglobin and a hematocrit, thrombocytopenia.

Disturbances from immune system: frequency is unknown – hypersensitivity reactions, including a serum disease.

Disturbances from a metabolism and food: frequency is unknown – the increased potassium concentration in blood serum, a hyponatremia.

Disturbances from an acoustic organ and labyrinth disturbances: infrequently – вертиго.
Disturbances from vessels: frequency is unknown – a vasculitis.

Disturbances from a GIT: infrequently – an abdominal pain.

Disturbances from a liver and biliary tract: frequency is unknown – increase in the indicators characterizing function of a liver.

Disturbances from skin and hypodermic fabrics: frequency is unknown – a Quincke's disease, skin rash, a skin itch.

Disturbances from kidneys and urinary tract: frequency is unknown – a renal failure.

Hydrochlorthiazidum. The following undesirable phenomena were noted at monotherapy by Hydrochlorthiazidum, irrespective of relationship of cause and effect with this drug:

Disturbances from blood and lymphatic system: seldom – thrombocytopenia (sometimes with a purpura); very seldom – an agranulocytosis, a leukopenia, hemolitic anemia, oppression of function of marrow; frequency is unknown – aplastic anemia.

Disturbances from immune system: very seldom – hypersensitivity reactions.

Disturbances from a metabolism and food: very often – a hypopotassemia, increase in level of lipids in blood (it is preferential at reception of high doses of drug); often – a hyponatremia, a hypomagnesiemia, a hyperuricemia; seldom – a hypercalcemia, a hyperglycemia, a glucosuria and an aggravation of symptoms of patients with diabetes; very seldom – a gipokhloremichesky alkalosis.

Disturbances of mentality: seldom – a depression, frustration of a dream.

Disturbances from a nervous system: seldom – a headache, dizziness, paresthesia.

Disturbances from an organ of sight: seldom – a vision disorder; frequency is unknown – acute closed-angle glaucoma.

Disturbances from heart: seldom – arrhythmia.

Disturbances from vessels: often – orthostatic hypotension.

Disturbances from respiratory system, bodies of a thorax and a mediastinum: very seldom – a respiratory distress syndrome with a pneumonitis and a fluid lungs.

Disturbances from a GIT: often – a loss of appetite, nausea, vomiting; seldom – a lock, discomfort in a GIT, diarrhea; very seldom – pancreatitis.

Disturbances from a liver and biliary tract: seldom – an intra hepatic cholestasia or jaundice.

Disturbances from kidneys and urinary tract: frequency is unknown – a renal failure, an acute renal failure.

Disturbances from skin and hypodermic fabrics: often – a small tortoiseshell and other forms of rash; seldom – photosensitivity reactions; very seldom – the necrotizing vasculitis, a toxic epidermal necrolysis (Lyell's disease), skin reactions reminding the system lupus erythematosus (SLE), a hard currency aggravation; frequency is unknown – a multiformny erythema.

The general frustration and disturbances in an injection site: frequency is unknown – temperature increase, an adynamy.

Disturbances from skeletal and muscular and connecting fabric: frequency is unknown – muscular spasms.

Disturbances from generative organs and a mammary gland: often – erectile dysfunction.

If any of the side effects specified in the instruction are aggravated, or you noticed any other side effects which are not specified in the instruction, report about it to the doctor.

Interaction with other medicines:

Your attending physician has to be informed on all medicine which you take. Before reception of any medicine during treatment by Co-Valsartan consult with the attending physician.

The interactions concerning a valsartan and Hydrochlorthiazidum. Lithium: it was reported about reversible increase in serumal concentration of lithium and increase in toxicity at simultaneous use with APF inhibitors and tiazida. Experience of simultaneous use of a valsartan and drugs of lithium is limited therefore it is not recommended to combine these drugs. If the concomitant use of these drugs is necessary, careful control of serumal concentration of lithium is recommended.

Other anti-hypertensive drugs: Ko-Valsartan can strengthen action of other anti-hypertensive means (гуанетидин, Methyldopum, vazodilatator, APF inhibitors, beta adrenoblockers, blockers of calcium channels).

Sympathomimetics (adrenaline, noradrenaline): weakening of the therapeutic answer to sympathomimetics is possible.

Non-steroidal anti-inflammatory drugs (NPVS), including the selection inhibitors of cyclooxygenase-2 (TsOG-2), acetylsalicylic acid (more than 3 g/days) and other non-selective NPVS: at co-administration weakening of anti-hypertensive action, and also increase in risk of deterioration in function of kidneys and increase in plasma potassium concentration is possible. In case of need uses of a similar combination should be provided adequate hydration of patients and control of function of kidneys from an initiation of treatment.

The interactions arising at treatment by separate active components of drug can arise also at treatment by this drug.

The interactions concerning a valsartan. Double blockade system renin-angiotensin-aldosteronovoy (SRAA) of the SCONCE II, APF inhibitors or aliskireny: it is necessary to apply with care the SCONCE of II, including валсартан, along with other medicines blocking RAAS – i.e. with APF inhibitors or with aliskireny.

Contraindicated simultaneous use of the SCONCE of II, including валсартан, or APF inhibitors with aliskireny at patients with a diabetes mellitus or a moderate / heavy renal failure (SKF <60 ml/min. / 1,73м2).

The Kaliysberegayushchy diuretics, drugs of potassium and substitutes of salt containing potassium: if simultaneous use of a valsartan with the drug influencing potassium concentration in blood serum is recognized as necessary, it is recommended to control potassium concentration in blood serum.

Conveyors: these in vitro show what валсартан is substrate for proteins carriers of OATP1B1/OATP1B3 and MRP2. Simultaneous use with inhibitors of proteins carriers OATP1B1/OATP1B3 (Rifampinum, cyclosporine) or efflyuksny protein carrier MRP2 (ритонавир) can increase system exposure of a valsartan. Special precautionary measures have to be undertaken at the beginning or at the end of joint therapy by the specified medicines.

Others: clinically significant interactions with such medicines, as: Cimetidinum, warfarin, furosemide, digoxin, атенолол, indometacin, Hydrochlorthiazidum, амлодипин and Glibenclamidum it is not revealed.

The interactions concerning Hydrochlorthiazidum. The drugs influencing potassium level in blood: the gipokaliyemichesky effect of diuretic can amplify at a concomitant use of other potassiumuretic diuretics, corticosteroids, laxatives, adrenocorticotropic hormone, Amphotericinum, a karbenoksolon, penicillin G, salicylic acid and salicylates), it is regularly recommended to control potassium concentration in plasma.

The drugs causing cardiac arrhythmias: because of risk of development of a hypopotassemia it is necessary to be careful at simultaneous use of the drugs causing cardiac arrhythmias like "pirouette" (torsades de pointes): antiarrhytmic means of a class 1a and III, some antipsychotic means.

The drugs influencing sodium level in blood: the giponatriyemichesky effect of diuretics can amplify at simultaneous use with some medicines, such as antidepressants, antipsychotic means and antiepileptic means. It is recommended to be careful at long-term use of these medicines.

Cardiac glycosides: the hypopotassemia and a hypomagnesiemia caused by reception of thiazide diuretics promote development of cardiac arrhythmias at reception of cardiac glycosides.

Salts of calcium and vitamin D: use of thiazide diuretics, including Hydrochlorthiazidum, with vitamin D or salts of calcium can lead to increase in concentration of calcium in serum and to development of a hypercalcemia in patients with predisposition (for example, at a hyperparathyreosis) owing to increase in a canalicular reabsorption of calcium.

Antidiabetic means (peroral antihyperglycemic means and insulin): tiazida can break tolerance to glucose. At use of thiazide diuretics dose adjustment of antidiabetic means can be required. It is necessary to be careful at Metforminum use since development of a lactacidemia owing to development of a functional renal failure against the background of reception of Hydrochlorthiazidum is possible.

Beta-blockers and diazoxide: simultaneous use of thiazide diuretics, including Hydrochlorthiazidum, with beta adrenoblockers can increase risk of development of a hyperglycemia. Thiazide diuretics can strengthen hyper glycemic effect of diazoxide.

Medicines for treatment of gout (пробенецид, Sulfinpyrazonum and Allopyrinolum): dose adjustment of drugs for treatment of gout in view of possible increase by Hydrochlorthiazidum of serumal concentration of uric acid can be required. If necessary it is necessary to increase a dose of a probenetsid or Sulfinpyrazonum. Simultaneous use of thiazide diuretics, including Hydrochlorthiazidum, can increase the frequency of development of reactions of hypersensitivity to Allopyrinolum.

The anticholinergics and other medicines influencing motility of a GIT: anticholinergics (atropine, Biperidinum) can increase bioavailability of thiazide diuretics, obviously, owing to oppression of motility of digestive tract and reduction of speed of gastric emptying. Prokinetics, such as цизаприд, on the contrary, can reduce bioavailability of thiazide diuretics.

Amantadin: thiazide diuretics can increase risk of development of undesirable effects of an amantadin.

Ion-exchange resins: absorption of Hydrochlorthiazidum worsens in the presence of Colestyraminum and a kolestipol. It is recommended to accept Hydrochlorthiazidum in 4 hours prior to or in 4-6 hours after reception of ion-exchange resins.

Cytotoxic means: Hydrochlorthiazidum can reduce renal excretion of cytotoxic drugs (cyclophosphamide, a methotrexate) and to exponentiate their myelosuppressive action.

Not depolarizing muscle relaxants (tubocurarine): Hydrochlorthiazidum exponentiates action of kurarepodobny muscle relaxants.

Cyclosporine: at simultaneous use with cyclosporine the risk of development of a hyperuricemia and complications like gout increases.

Alcohol, barbiturates and drugs: combined use of thiazide diuretics with the substances possessing hypotensive action can increase risk of development of orthostatic hypotension.

Methyldopum: it was reported about separate cases of development of hemolitic anemia against the background of a concomitant use of Hydrochlorthiazidum and Methyldopums.

Iodinated contrast agents: at dehydration caused by use of thiazide diuretics there is an increased risk of development of an acute renal failure, especially at use of high doses of iodinated drugs. Patients need a regidratation before administration of iodinated drugs.

Contraindications:

- Hypersensitivity to a valsartan, Hydrochlorthiazidum, sulfonamides or to any other component of drug;

- pregnancy and feeding by a breast;

- heavy abnormal liver functions, biliary cirrhosis and cholestasia;

- anury, heavy renal failure (SKF <30 ml/min. / 1,73 sq.m);

- refractory hypopotassemia, hyponatremia, hypercalcemia and symptomatic hyperuricemia;

- children's and teenage age up to 18 years (safety and efficiency of use for children aged up to 18 years are not established);

- simultaneous use of the SCONCE of II, including валсартан, or APF inhibitors with aliskireny at patients with a diabetes mellitus or a moderate / heavy renal failure (SKF <60 ml/min. / 1,73м2).

Overdose:

At reception bigger, than it is registered by the doctor, doses of medicine it is necessary to address immediately specialists for rendering timely medical care!

Symptoms: the overdose valsartany can cause the expressed hypotension which, in turn, can lead to consciousness disturbance, a circulator collapse and/or shock. At overdose by Hydrochlorthiazidum development of nausea, drowsiness, a hypovolemia, disturbance of the balance of electrolytes which is followed by cardiac arrhythmias and muscular spasms is possible.

Treatment: therapeutic actions depend on prescription of reception of an excess dose, and also a look and weight of symptoms, at the same time a priority action is stabilization of cardiovascular system. At overdose depending on time which passed after administration of drug, the taken measures have to include stimulation of vomiting, a gastric lavage and/or reception of absorbent carbon.

At hypotension it is necessary to lay the patient in horizontal position and to urgently provide recovery of water-salt balance by introduction of isotonic saline solution.

Valsartan is not brought by means of a hemodialysis because of its strong linkng with proteins of plasma, however for removal from Hydrochlorthiazidum organism the hemodialysis is effective.

Storage conditions:

In the place protected from light and moisture, at a temperature not over 25 ºС. To store in the place, unavailable to children. Period of validity 2 years.

Issue conditions:

According to the recipe

Packaging:

Tablets, coated, 160 mg / 12,5 mg.

On 10 tablets in a blister strip packaging. 3 blister strip packagings with the instruction on a medical use place in a pack cardboard.

On 15 tablets in a blister strip packaging. 2 blister strip packagings with the instruction on a medical use place in a pack cardboard.