Pharmacological properties

Pharmacodynamics. valsartan / hydrochlorothiazide. positive influence of a valsartan in a combination with a hydrochlorothiazide on the cardiovascular mortality and incidence it is still unknown.

Epidemiological researches showed that long-term treatment by a hydrochlorothiazide reduces risk of cardiovascular mortality and incidence.

Valsartan. Valsartan is a specific antagonist of receptors of angiotensin II (Ang II). It selectively influences a subtype of a receptor AT ₁ which is responsible for the known effect of angiotensin II. At increase in concentration of angiotensin II after blockade of a receptor of AT ₁ owing to reception of a valsartan can stimulate not blocked receptor of AT ₂ establishing balance between effect of a receptor of AT _{1 in blood plasma} . Valsartan does not show any partial agonistic action on receptors of AT ₁ and is characterized much big (about 20 000-fold) by affinity to receptors of AT ₁ , than to receptors of AT ₂ . It is unknown whether contacts valsartan other hormonal receptors or ion channels important in the course of cardiovascular regulation, and whether it blocks them.

Valsartan is not inhibited by APF also known as kininaz of II who converts angiotensin I into angiotensin II and leads to bradykinin disintegration. As the effect on APF is absent and there is no potentsiation of bradykinin or substance P, antagonists of angiotensin II it is improbable cause cough. When comparing a valsartan with APF inhibitor the frequency of developing of dry cough is much lower at the patients receiving valsartan in comparison with patients who receive APF inhibitors.

Use of a valsartan for patients with AG leads

to decrease in the ABP, without affecting pulse rate. At most of patients after introduction of a single oral dose the approach of hypotensive effect arises within 2 h, and peak decrease in the ABP is reached during 4–6 h. The hypotensive effect lasts for 24 h after reception. At repeated reception the maximum decrease in the ABP irrespective of a dose, as a rule, is reached during 2–4 weeks and remains at prolonged use. In a combination with a hydrochlorothiazide the considerable additional decrease in the ABP is reached.

Sharp termination of reception of a valsartan does not cause "ricochet" AG or other by-effects.

Hydrochlorothiazide. The scene of action of thiazide diuretics is generally distal gyrose a renal tubule. At cortical substance of kidneys there is a receptor with high degree of affinity acting as the main binding site for effect of thiazide diuretics and inhibition of transportation of NaCl in a distal wavy renal tubule. The mechanism of action of tiazid is implemented by inhibition of a simporter of Na ⁺ Cl ^– probably owing to the competition for the site of Cl ^– that influences mechanisms of an electrolytic reabsorption: direct increase in level of sodium and removal of chloride approximately equally and indirect effect of this diuretic which reduces level in blood plasma with the subsequent increase in activity of renin of blood plasma, secretion of Aldosteronum and decrease in level of potassium in urine and also decrease in potassium in blood plasma. Communication between renin and Aldosteronum is mediated by angiotensin II therefore at simultaneous use of a valsartan decrease in potassium in blood plasma less expressed, than at monotherapy with a hydrochlorothiazide.

Pharmacokinetics. Valsartan / hydrochlorothiazide. System availability of a hydrochlorothiazide decreases approximately by 30% at simultaneous use with valsartany. The kinetics of a valsartan does not undergo considerable influence at simultaneous use with a hydrochlorothiazide. Such obvious interaction does not influence the combined use of a valsartan and hydrochlorothiazide as the accurate hypotensive effect of a combination exceeds the effect reached at monotherapy by any of active agents or placebo.

Valsartan. Absorption. After oral administration of a valsartan its peak concentration in blood plasma are reached in 2–4 h. Average absolute bioavailability — 23%. Meal reduces influence (AUC is measured) a valsartana approximately by 40% and the C _max in blood plasma approximately by 50% though, beginning approximately with 8 h after reception, concentration of a valsartan in blood plasma is similar at the patients who ate food and at the patients who used medicament on an empty stomach. Such reduction of AUC, however, is not followed by clinically significant decrease in therapeutic effect therefore valsartan it is possible to accept irrespective of meal.

Distribution. The stable volume of distribution of a valsartan in/in introductions is later 17 l, and it demonstrates to what valsartan is inactively distributed in fabrics. Valsartan actively contacts proteins of blood plasma (94–97%), in particular blood plasma albumine.

Biotransformation. Valsartan biotransformirutsya in insignificant quantity as only 20% of a dose are restored in the form of metabolites. The hydroxyl metabolite is revealed in blood plasma in small concentration (10% of AUC for a valsartan). This metabolite is inactive from the pharmacological point of view.

Removal. Valsartan shows kinetics of multiexponential disintegration (T _½ α through 1 h and T _½ ß later about 9 h). Valsartan is brought generally with a stake (about 83% of a dose) and urine (about 13% of a dose) in not changed look. After introduction the clearance of a valsartan is of blood plasma ≈2 l/h, and renal clearance — 0.62 l/h (about 30% of the general clearance). T _½ a valsartana — 6 h

Hydrochlorothiazide. Absorption. Absorption of a hydrochlorothiazide after oral administration happens quickly (Tmax of ≈2 h), characteristics of absorption similar for dosage forms suspension and tablets. The bioavailability of a hydrochlorothiazide is 60–80% after oral administration. It was reported that the concomitant use with food leads as to increase, and decrease in system bioavailability of a hydrochlorothiazide in comparison with a state on an empty stomach. Frequency of fluctuations of such effects is low and has the minimum clinical importance. Increase in the average size AUC is linear and proportional to a dose within the range of therapeutic dosing. There are no changes in hydrochlorothiazide kinetics at a repeated dosage, and cumulation is minimum at the mode of dosing of 1 times a day.

Distribution. The kinetics of distribution and removal is described in general by the biexponentsialny descending curve. The volume of distribution is 4–8 l/kg. The hydrochlorothiazide in general circulation contacts proteins of blood plasma (40–70%), mainly blood plasma albumine.

Hydrochlorthiazidum also accumulates in erythrocytes, approximately by 1.8 times exceeding level in blood plasma.

Removal. More than 95% of a dose of a hydrochlorothiazide which was soaked up, removed in not changed view with urine. Discharge kidneys consists of passive filtration and active secretion in tubules of kidneys. Final the T _½ makes 6–15 h

Special groups of patients

Elderly person. Slightly more system exposure to a valsartan is noted at some elderly people in comparison with young faces; however it was not shown that it has any clinical value.

Limited data indicate

that the system clearance of a hydrochlorothiazide decreases both at healthy faces of advanced age, and at elderly people with AG in comparison with healthy young volunteers.

Renal failure. At the recommended dose valsartana / the hydrochlorothiazide is not required to dose adjustment for patients with clearance of creatinine of 30-70 ml/min.

Concerning patients with heavy renal failures (clearance of creatinine of 30 ml/min.) and there are no patients receiving dialysis sessions data for valsartana / a hydrochlorothiazide. Valsartan very strongly contacts proteins of blood plasma and is not brought by means of dialysis, and the clearance of a hydrochlorothiazide is reached by means of dialysis.

Clearance of a hydrochlorothiazide kidneys consists of passive filtration and active secretion in tubules of kidneys. As well as it is expected for substance which is almost completely emitted with kidneys, function of kidneys renders noticeable effect on hydrochlorothiazide kinetics.

Abnormal liver function. There are no data on use of a valsartan for patients with heavy disturbances of a liver. The liver disease considerably does not influence hydrochlorothiazide pharmacokinetics.

Indication

Ag at patients whose hell is not regulated as a result of monotherapy use.

Use

Recommended dose — 1 tablet a valsakor n80 (80 mg / 12.5 mg) in day. in case of insufficient decrease hell in 3–4 weeks after an initiation of treatment h160 valsakor (160 mg / 12.5 mg) 1 time a day is recommended to consider the possibility of increase in a dose to 1 tablet. patients at whom sufficient decrease hell is not reached at use h160 valsakor should appoint hd160 valsakor (160 mg / 25 mg).

in case of insufficient decrease the ABP at reception Valsakor of HD160 should begin treatment with tablets valsartana / a hydrochlorothiazide of 320 mg / 12.5 mg (Valsakor of H320). Tablets valsartana / a hydrochlorothiazide of 320 mg / 25 mg (Valsakor HD320) should be applied at patients at whom control of the ABP is insufficient at reception of tablets valsartana / a hydrochlorothiazide of 320 mg / 12.5 mg.

Maximum daily dose — 320 mg / 25 mg.

Antihypertensive effect mainly is noted in the first 2 weeks. At most of patients the maximum effect is shown during 4 weeks. However for some patients 4–8 weeks of treatment can be required. It should be considered at selection of a dose.

Valsakor of H80, Valsakor of H160, Valsakor of HD160, Valsakor N 320 and Valsakor HD 320 it is possible to apply irrespective of meal, washing down with water.

Renal failure. For patients with a renal failure easy or moderate severity is not required dose adjustments (glomerular filtration rate (GFR) of ≥30 ml/min). Because of the maintenance of a hydrochlorothiazide medicament is contraindicated to patients with a heavy renal failure (SKF of 30 ml/min.) and an anury (see CONTRAINDICATIONS, INTERACTIONS and Pharmacokinetics). Simultaneous use with aliskireny is contraindicated to patients with a renal failure (SKF of 60 ml/min. / 1.73 m ² ) (see CONTRAINDICATIONS).

Liver failure. At patients with a liver failure easy and moderate severity without existence of a cholestasia a dose of a valsartan should not exceed 80 mg (see. Special INSTRUCTIONS). Dose adjustment of a hydrochlorothiazide is not required from patients with a liver failure easy and moderate severity. Because of the maintenance of a valsartan medicament is contraindicated to patients with a heavy liver failure or biliary cirrhosis and a cholestasia (see CONTRAINDICATIONS, SPECIAL INSTRUCTIONS and Pharmacokinetics).

Diabetes. Simultaneous use of a valsartan and aliskiren is contraindicated to patients with diabetes (see CONTRAINDICATIONS).

Patients of advanced age. For patients of advanced age of dose adjustment it is not required.

Contraindication

Hypersensitivity to medicament components, hypersensitivity to derivatives of sulfonamides; heavy abnormal liver functions, cirrhosis and cholestasia, anury, heavy renal failures (clearance of creatinine of 30 ml/min.); refractory hypopotassemia, hyponatremia, hypercalcemia or symptomatic hyperuricemia; simultaneous use of antagonists of receptors of angiotensin, including a valsartan or inhibitors apf, with aliskireny at patients with diabetes or a renal failure (skf 60 ml/min. / 1.73 sq.m); the pregnant women or women planning pregnancy (see use during pregnancy and feeding by a breast).

Side effects

on the systems of bodies are given by

side reactions more often noted at reception of a combination of a valsartan and hydrochlorothiazide, than at intake of placebo about which it was reported during clinical trials and laboratory observations and also separate post-marketing messages Below. the side reactions arising at reception of each separate component, but which were not observed during clinical trials can appear during treatment by a combination of a valsartan and a hydrochlorothiazide.

Side reactions are distributed by

on emergence frequency: very often (≥1/10); often (≥1/100, 1/10); infrequently (≥1/1000, 1/100) it is rare (≥1/10,000, 1/1000); very seldom (1/10,000); it is unknown (it is impossible to determine by the available data).

side reactions are provided to

In each group on frequency as reduction of gravity.

Frequency of emergence of side reactions at reception valsartana / a hydrochlorothiazide

from metabolism and digestion: infrequently — dehydration.

from nervous system: very often — dizziness, a headache; infrequently — paresthesias; it is unknown — a loss of consciousness.

from an organ of sight: infrequently — the obscured sight, illegibility of sight, a disorder of vision.

from an organ of hearing: infrequently — a ring in ears, otitis of a middle ear.

from the vascular system: infrequently — arterial hypotension.

from a respiratory, thoracic system and mediastinum: infrequently — cough, a nasopharyngitis, an upper respiratory tract infection.

does not know to

: not cardiogenic fluid lungs, sinusitis, bronchitis.

from a digestive tract: very seldom — diarrhea.

from the bone and skeletal device and connective tissue: infrequently — myalgia; very seldom — an arthralgia, a dorsodynia.

from kidneys and urinary tract: it is unknown — a renal failure.

General disorders and disturbances of conditions of introduction: infrequently — fatigue.

Laboratory researches: it is unknown — increase in uric acid in blood plasma, increase in level of bilirubin and creatinine in blood plasma, a hypopotassemia, a hyponatremia, increase in urea nitrogen in blood, a neutropenia.

Additional information on separate components. Side reactions about which reported earlier at use of one of separate components can also appear during medicament treatment even if they were not observed during clinical trials or during the post-marketing period.

Frequency of emergence of side reactions at reception of a valsartan

from blood and lymphatic system: it is unknown — decrease in hemoglobin, decrease in a hematocrit, thrombocytopenia.

from the immune system: it is unknown — other reactions a hypersensitivity/allergy, including orrhoreaction.

from metabolism and digestion: it is unknown — increase in level of potassium in blood serum.

from an organ of hearing: infrequently — vertigo.

from the vascular system: it is unknown — a vasculitis.

from a digestive tract: infrequently — an abdominal pain.

from a liver and biliary tract: it is unknown — increase in level of hepatic test.

from skin and hypodermic fabrics: it is unknown — a Quincke's disease, rash, an itching.

from kidneys and urinary tract: it is unknown — a renal failure.

Frequency of emergence of side reactions at reception of a hydrochlorothiazide

from blood and lymphatic system: seldom — thrombocytopenia, sometimes with a purpura; very seldom — an agranulocytosis, a leukopenia, hemolytic anemia, oppression of function of marrow.

from the immune system: very seldom — hypersensitivity reactions.

Mental disturbances: seldom — a depression, sleep disorders.

from nervous system: seldom — a headache, dizziness, paresthesias, disorders of vision.

from a cardiovascular system: seldom — cardiac arrhythmias.

from the vascular system: often — postural hypotension.

from a respiratory, thoracic and madiastinalny system: very seldom — an apnoea, including a pneumonitis and a fluid lungs.

from digestive system: often — loss of appetite, slight nausea and vomiting; seldom — a constipation, discomfort in a digestive tract; very seldom — pancreatitis.

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

from skin and hypodermic fabrics: often — a small tortoiseshell and other forms of rashes; seldom — photosensitivity; very seldom — a necrotizing vasculitis and a toxic epidermal necrolysis of skin, the skin reactions similar to reaction of a system lupus erythematosus, reactivation of skin manifestations of a lupus erythematosus.

from a reproductive system and mammary glands: often — impotence.

Change of electrolytes and metabolism: it was reported about hypopotassemia cases at treatment by thiazide diuretics. Treatment by thiazide diuretics is often connected with emergence of a hyponatremia and a gipokhloremichesky alkalosis. Tiazida strengthen removal of magnesium with urine that as a result can lead to a hypomagnesiemia.

At emergence of heavy side effects administration of medicament should be stopped.

Special instructions

Renal failure and transplantation of a kidney. patients with a transplant of a kidney should not take the drug. persons with a renal failure do not require dose adjustment if clearance of creatinine of ≥30 ml/min. because of the maintenance of a hydrochlorothiazide h80 valsakor, h160 valsakor, hd160 valsakor, a valsakor of N 320 and a valsakor nd 320 are contraindicated to patients with a heavy renal failure (clearance of creatinine of 30 ml/min.) and an anury. it is recommended to control periodically the level of potassium, creatinine and uric acid in blood plasma.

Thiazide diuretics can provoke an azotemia at patients with a chronic renal failure.

Renal artery stenosis. As there is a probability of increase in level of urea and creatinine in blood plasma, patients about one - or a bilateral renal artery stenosis or a stenosis of the only kidney are not recommended to take the drug.

Primary aldosteronism. Drug is not recommended to be used at patients with primary aldosteronism as the basic disease influences the renin-angiotensin-aldosteronovuyu system (RAAS).

Patients with heavy heart failure with the developments of stagnation or other states which are followed by stimulation of RAAS. Use of the means operating on RAAS can cause an oliguria and/or the progressing azotemia in patients at whom function of kidneys depends generally on activity of RAAS (for example patients with heavy heart failure with developments of stagnation), in rare instances with development of OPN. Safety of use of medicament for patients with heavy heart failure with developments of stagnation is not established. Therefore it is possible that in connection with oppression of RAAS at use of medicaments Valsakor H80, Valsakor of H160, Valsakor of HD160, Valsakor of N 320 and Valsakor of HD 320 can develop a renal failure. Such patients should not take the drug.

Change of balance of electrolytes in blood plasma. It is necessary to be careful at the combined intake of the nutritional supplements containing potassium; kaliysberegayushchy diuretics; salt substitutes which part potassium is; or other medicaments which can increase potassium concentration in blood (heparin).

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It was reported about development of a hypopotassemia during treatment by thiazide diuretics. It is regularly necessary to control potassium level in blood plasma.

Hydrochlorothiazide. The hypopotassemia was noted during treatment by thiazide diuretics, including a hydrochlorothiazide. It is recommended to conduct regular monitoring of level of potassium in blood plasma.

Treatment by thiazide diuretics, including a hydrochlorothiazide, causes a hyponatremia and a gipokhloremichesky alkalosis. Tiazida, including a hydrochlorothiazide, increase removal of magnesium with urine that can lead to a hypomagnesiemia. Removal of calcium decreases at intake of thiazide diuretics. It can lead to a hypercalcemia.

At patients who receive treatment by diuretics should carry out the periodic assessment of level of electrolytes in blood plasma with the corresponding frequency.

Should check regularly the level of electrolytes in blood plasma.

Patients with deficit in an organism of sodium and/or OCK. The patients accepting thiazide diuretics need to be observed concerning emergence of clinical manifestations of an imbalance of liquid or electrolytes. Dangerous signs of a water and electrolytic imbalance are dryness in a mouth, thirst, an asthenia (exhaustion, weakness), drowsiness, block, excitement (dysphoria), spasms or muscle pain, fatigue of muscles, arterial hypotension, an oliguria, tachycardia and gastrointestinal disorders (nausea and vomiting).

At patients with the significant deficiency of sodium and/or OCK in an organism (for example at use of diuretics in high doses) in some cases after the beginning of therapy by medicament symptomatic hypotension is possible

. Prior to therapy it is necessary to carry out correction of contents in an organism of sodium and/or OCK. In arterial hypotension the patient needs to give horizontal position with the raised lower extremities and to carry out parenteral administration of salt solutions. Treatment can be continued after stabilization of the ABP.

Stenosis of an aorta and mitral valve, subaortic hypertrophic stenosis. It is necessary to observe extra care to patients with a stenosis of an aorta or the mitral valve or with a subaortic hypertrophic stenosis.

Abnormal liver function. At patients with an insignificant or moderate abnormal liver function medicament is used with care, it is no more than 80 mg of a valsartan a day.

Because of the maintenance of a valsartan Valsakor of H80, Valsakor of H160, Valsakor of HD160, Valsakor of N 320 and Valsakor HD 320 are contraindicated to patients with a heavy liver failure or biliary cirrhosis and a cholestasia. With insignificant and moderate abnormal liver functions without cholestasia of dose adjustment of a hydrochlorothiazide it is not required from patients. However medicament should be used with care. Liver diseases slightly influence hydrochlorothiazide pharmacokinetics. Tiazida it is necessary to apply with care at patients with disturbances of functions of a liver or the progressing liver disease as minor changes of liquid or electrolytic balance can lead to a hepatic coma.

System lupus erythematosus. During reception of tiazid it was reported about aggravation or activation of a system lupus erythematosus.

Other metabolic disturbances. Thiazide diuretics can affect tolerance of glucose and increase level XC, TG and uric acid in blood plasma. Sick diabetes dose adjustment of insulin or oral gipoglikemiziruyushchy medicaments can be necessary.

Tiazida's

can reduce removal of calcium with urine and cause the alternating and slight increase of level of calcium in blood plasma in the absence of the known disturbances of metabolism of calcium. The expressed hypercalcemia can demonstrate existence of a hyper parathyroidism. Use of tiazid should be stopped before carrying out analyses of function of epithelial bodies.

Photosensitivity. Development of a photosensitization was noted at intake of thiazide diuretics (see. Side EFFECTS). In case of reaction of photosensitivity during medicament treatment it is recommended to stop therapy. In need of repeated intake of diuretic it is recommended to protect vulnerable zones from solar or artificial UV-radiation.

Acute closed-angle glaucoma. The hydrochlorothiazide causes the idiosyncratic reactions leading to development of a sharp tranzitorny myopathy and acute closed-angle glaucoma. Sharp decrease in visual acuity or pain in eyes which, as a rule, arise during the period of several hours to 1 week after administration of medicament belong to symptoms. The lack of treatment of acute closed-angle glaucoma can lead to final loss of sight.

Treatment by a hydrochlorothiazide should be stopped as soon as possible. The urgent medical or surgical care can be required if intraocular pressure remains uncontrollable. Risk factors of developing acute closed-angle glaucoma can include existence in the anamnesis of an allergy to sulfonamides or penicillin.

General disturbances. It is necessary to be careful at use of medicament for patients with hypersensitivity to other antagonists of receptors of angiotensin II. Patients with an allergy and OH in the anamnesis have a high probability of development of allergic reactions.

Quincke's disease. About developing of a Quincke's edema (including a laryngeal edema and a glottis which led to obstruction of airways and/or edema of face, lips, drinks and/or language) it was reported at the patients receiving valsartan. Some of them had in the anamnesis a Quincke's edema at use of other drugs, including other antagonists of receptors of angiotensin II. At edematization of Quincke the treatment by antagonists of receptors of angiotensin II should be stopped immediately. Repeated use of medicament is contraindicated.

Double blockade of RAAS. AG, a syncope, the stroke, a hyperpotassemia and changes of function of kidneys, including OPN, were observed at susceptible patients, especially at a combination of the medicines influencing this system. Due to the double blockade of RAAS the simultaneous use of an aliskiren and antagonists of receptors of angiotensin II or APF inhibitors is not recommended.

Hydrochlorothiazide can reduce the level of the iodine connected with proteins in blood plasma.

Hydrochlorothiazide is capable to increase concentration of free bilirubin in blood plasma. to Patients of advanced age of dose adjustment it is not required by

to p.

Important information on some ingredients. Valsakor of H80, Valsakor of H160, Valsakor of HD160, Valsakor of N 320 and Valsakor HD 320 contain lactose. Patients with rare hereditary forms of intolerance of a galactose, deficiency of Lappa lactase or malabsorption of glucose galactose should not appoint this drug.

Use during pregnancy and feeding by a breast

Pregnancy

Valsartan. Use of antagonists of receptors of angiotensin II is contraindicated during pregnancy. Epidemiological data on risk of teratogenecity as a result of effect of APF inhibitors in the I trimester of pregnancy are ambiguous; however slight increase of risk is not excluded. If continuous therapy by antagonists of receptors of angiotensin II is not considered necessary critically, patients who plan pregnancy should pass to alternative hypotensive treatment with the checked safety profile for use during pregnancy. When determining pregnancy the reception of antagonists of receptors of angiotensin II should be stopped immediately and if necessary to begin alternative treatment.

Reception of antagonists of receptors of angiotensin II in II and III trimester of pregnancy induces a fetotoksichnost at the person (deterioration in renal function, oligogidramnion, delay of ossification of bones of a skull) and neonatal toxicity (renal failure, arterial hypotension, a hyperpotassemia). Babies whose mothers antagonists of receptors of angiotensin II accepted should carry out careful monitoring on presence of arterial hypotension.

Hydrochlorothiazide. Experience of use of a hydrochlorothiazide during pregnancy, especially in the III trimester, is limited. These researches on animals are not enough. The hydrochlorothiazide gets through a placental barrier. Taking into account the pharmacological mechanism of action of a hydrochlorothiazide its use in II and III trimester can lead to disturbance of fetoplacental blood circulation and cause such fetal and neonatal effects as jaundice, disturbance of water-salt balance and thrombocytopenia.

Feeding by a breast

to

Information on use of a valsartan during feeding by a breast is inaccessible to

. The hydrochlorothiazide gets into breast milk in insignificant quantity. Tiazida in the high doses causing an intensive diuresis can inhibit producing milk. Thus, use valsartana / a hydrochlorothiazide during feeding by a breast is not recommended. It is desirable to carry out alternative treatment with the checked safety profile during feeding by a breast, especially when feeding by a breast of newborn or premature children.

Children. Safety and efficiency of use of medicament for children are not established therefore it is not used in pediatric practice.

Ability to influence speed of response at control of vehicles or work with other mechanisms. At the beginning of medicament use (the period is defined by the doctor) it is forbidden to run vehicles and to perform work with other mechanisms. Later extent of the ban is defined by the doctor.

Simultaneous use is not recommended to

Interaction

by

Interaction with a combination of a valsartan and a hydrochlorothiazide

Lities. It was reported about reversible increase in concentration of lithium in blood plasma and toxicity at the accompanying intake of lithium and APF inhibitors and/or tiazid. There is no experience of a concomitant use of a valsartan and lithium; therefore it is recommended to control concentration of lithium in blood plasma.

Accompanying use demanding extra care

Other antihypertensive drugs. Drug can enhance hypotensive effect of other antihypertensive medicaments (for example APF inhibitors, blockers of β-adrenoceptors, blockers of calcium channels).

Pressor amines (for example Norepinephrinum, epinephrine). Reliable decrease in reaction to pressor amines. The clinical importance of this effect is authentically unknown and insufficient to exclude their use.

NPVP, including selection TsOG-2 inhibitors, acetylsalicylic acid (3 g/days) and non-selective NPVP. NPVP can weaken hypotensive effect of both antagonists of angiotensin II, and a hydrochlorothiazide at their simultaneous use. Besides, the combined use valsartana / a hydrochlorothiazide and NPVP can lead to depression of function of kidneys and level of potassium in blood plasma. Thus, it is recommended to conduct monitoring of function of kidneys in an initiation of treatment and also to provide to the patient appropriate completion of loss of liquid.

Interaction, connected with valsartany

Double blockade of RAAS by antagonists of receptors of angiotensin II, APF inhibitors or aliskireny. It is necessary to be careful at simultaneous use of medicaments of group of antagonists of receptors of angiotensin II, including a valsartan, with other medicaments blocking RAAS, such as medicaments of group of APF inhibitors or aliskiren (see. Special INSTRUCTIONS).

Co-administration of antagonists of a receptor of angiotensin, including valsartan, or APF inhibitors with aliskireny to patients with diabetes or a renal failure (SKF of 60 ml/min. / 1.73 m ² ) is contraindicated (see CONTRAINDICATIONS).

Simultaneous use is not recommended to

Kaliysberegayushchy diuretics, potassium drugs, the salt substitutes containing potassium, and other substances which can increase potassium level. It is necessary to be careful at a concomitant use of the medicaments influencing potassium level. It is recommended to control often potassium level in blood plasma.

Lack of interactions

In researches with valsartany no clinically significant interactions are revealed by

at reception of a valsartan with any of the following substances: Cimetidinum, warfarin, furosemide, digoxin, atenolol, indometacin, hydrochlorothiazide, amlodipin and glibenclamide. Digoxin and indometacin can enter interaction with a hydrochlorothiazide as a part of the medicaments Valsakor H80, Valsakor H160, Valsakor HD160, Valsakor H320 and Valsakor HD320 (see the Interactions connected with a hydrochlorothiazide).

Interaction, connected with a hydrochlorothiazide

Simultaneous use requiring special attention

Medicines influencing