Valsartan trade names. Valsartan-nan: instructions for use. Terms and conditions of storage

Active ingredients: valsartan, hydrochlorothiazide.

A cardiological drug that has an antihypertensive, diuretic effect.

Pharmacodynamics. Valsartan binds to specific AT 1 angiotensin II receptors located in the vessels, heart, kidneys, brain, lungs and adrenal cortex and competitively blocks them. Suppresses all mediated through AT 1 receptor effects of angiotensin II, incl. vasoconstriction and secretion of aldosterone. Causes a decrease in blood pressure, not accompanied by a change in heart rate. Reduces myocardial hypertrophy in patients with arterial hypertension. Does not affect the content of total cholesterol, triglycerides, glucose and uric acid.

Hydrochlorothiazide is a medium strength thiazide diuretic. Reduces Na reabsorption+ at the level of the cortical segment of the loop of Henle. Blocks carbonic anhydrase in the proximal convoluted tubule, enhances urinary excretion of K+ (in the distal tubules Na+ exchanged for K+ ), hydrocarbonates and phosphates. Virtually no effect on the acid-base state (Na+ excreted either together with Cl- , or with bicarbonate, therefore, with alkalosis, the excretion of bicarbonate increases, with acidosis - Cl- ). Increases excretion of Mg 2+ , retains Ca ions in the body 2+ and urates.

Pharmacokinetics. The diuretic effect develops after 1-2 hours, reaches a maximum after 4 hours, lasts 10-12 hours. The action decreases with a decrease in the glomerular filtration rate and stops when it is less than 30 ml / min. It lowers blood pressure by reducing BCC, changing the reactivity of the vascular wall, reducing the pressor effect of vasoconstrictor drugs (epinephrine, norepinephrine). The maximum hypotensive effect is observed in the first 2-4 weeks of treatment.

When used together with valsartan, the systemic bioavailability of hydrochlorothiazide decreases by about 30%, hydrochlorothiazide does not significantly affect the kinetics of valsartan. The noted interaction does not affect the effectiveness of the combined application.

Arterial hypertension (with the ineffectiveness of valsartan monotherapy), reduced risk of cardiovascular morbidity and mortality in patients with arterial hypertension and left ventricular hypertrophy.

Inside, 1 tab. 1 time per day, daily (80 mg of valsartan and 12.5 mg of hydrochlorothiazide; for those patients who are shown to further reduce blood pressure, 160/12.5 mg, respectively).

Use during pregnancy and lactation. Category of action on the fetus according to the FDA - D.

Before treatment, the content of Na + in the blood and / or BCC is corrected. Regular monitoring of plasma levels of K+, glucose, uric acid, fats and creatinine is required. If pregnancy occurs during treatment, the drug should be discontinued.

During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require an increased concentration of attention and speed of psychomotor reactions.

According to the State Register, the following side effects were observed in patients receiving the valsartan-hydrochlorothiazide combination: fatigue, abdominal pain, rhinitis, viral infections, decreased hematocrit, hypercreatininemia, chest pain, allergic reactions, angioedema, pruritus, dysfunction kidneys.

According to the PDR, in patients treated with the valsartan-hydrochlorothiazide combination, the following adverse effects were noted during controlled clinical trials (which had a frequency of more than 2% and were more common on the background of drugs - the first number in brackets than in the placebo group - the second number in brackets) : dizziness (9%/7%), viral infections (3%/1%), fatigue (5%/1%), pharyngitis (3%/1%), cough (3%/0%), diarrhea (3 %/0%).

Headache, back pain and chest pain were observed in more than 2% of patients, but with approximately the same frequency in the control group and in the placebo group.

Dose-dependent orthostatic effects were observed in less than 1% of patients. A dose-dependent increase in the frequency of dizziness was observed when taking doses of the combination of valsartan-hydrochlorothiazide 80/12.5 mg (6%) and 160/25 mg (16%).

Other side effects observed in more than 0.2% of patients in controlled clinical trials, regardless of the causal relationship with the combination:

From the nervous system and sensory organs: asthenia, depression, insomnia, paresthesia, drowsiness, vertigo, tinnitus, visual impairment.

From the side of the cardiovascular system and blood (hematopoiesis, hemostasis): palpitations, syncope,.

From the digestive tract: increased appetite, constipation, dry mouth, abdominal pain, nausea, vomiting.

From the musculoskeletal system: arthralgia, muscle spasms, muscle weakness, pain in the arm, pain in the leg.

From the genitourinary system: increased urination, urinary tract infection.

Allergic reactions: rash, anaphylaxis.

Others: peripheral edema, flushing, erythema, increased sweating, dehydration, decreased libido, impotence.

It enhances the neurotoxicity of salicylates, the side effects of cardiac glycosides, the cardiotoxic and neurotoxic effects of lithium preparations, the effectiveness of curare-like muscle relaxants.

Reduces the excretion of quinidine, weakens the effect of oral hypoglycemic drugs, norepinephrine, epinephrine and anti-gout drugs.

Increases the frequency of allergic reactions to allopurinol; reduces the excretion of cytotoxic drugs by the kidneys (cyclophosphamide, methotrexate) and leads to an increase in their myelosuppressive effect.

Drugs that are intensively bound to blood proteins (indirect anticoagulants, clofibrate, NSAIDs) increase the diuretic effect.

The hypotensive effect is enhanced by vasodilators, beta-blockers, barbiturates, phenothiazines, tricyclic antidepressants, ethanol.

With the simultaneous administration of methyldopa, hemolysis may develop; cholestyramine reduces absorption.

Hypersensitivity; biliary cirrhosis, obstruction of the biliary tract; , (Cl creatinine).

Symptoms: decrease in blood pressure.

Treatment: gastric lavage, intravenous administration of 0.9% sodium chloride solution. effective against hydrochlorothiazide.

Valsartan is an angiotensin II receptor antagonist.

Release form and composition

Dosage forms:

• film-coated tablets: round, biconvex, light pink in color, the core is almost white or white, in tablets at a dose of 40 mg and 80 mg - a dividing line on one side (7, 10, 14, 20, 28, 30 or 56 pcs in a blister pack, in a carton box 1, 2, 3, 4, 5, 6, 8 or 10 packs, 7, 10, 14, 20, 28, 30, 40, 50 or 100 pcs. in a polymer jar, in a cardboard bundle 1 bank);
• capsules: hard gelatin, opaque, size No. 2 (capsules 20, 40, 80 mg), size No. 0 (capsules 160 mg); capsules 20 mg - light yellow, body - with a beige tint, cap - with a cream tint; capsules 40 mg - body and cap light yellow with a creamy tint; capsules 80 mg - body and cap light yellow with a beige tint; capsules 160 mg - light brown body and cap (10, 20 or 30 pieces in a blister pack, in a carton box 1, 2, 3, 4, 5 or 10 packs; 10, 20, 30, 40, 50 or 100 pieces in a polymer can, in a cardboard bundle 1 can).

1 tablet contains:

• active ingredient: valsartan - 40 mg, 80 mg or 160 mg;
• auxiliary components: microcrystalline cellulose, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate;
• shell composition: Opadray pink (macrogol-3350, polyvinyl alcohol, talc, titanium dioxide, iron dye yellow oxide, iron dye red oxide).

1 capsule contains:

• active ingredient: valsartan - 20 mg, 40 mg, 80 mg or 160 mg;
• auxiliary components: microcrystalline cellulose, croscarmellose sodium, povidone K17, colloidal silicon dioxide, magnesium stearate;
• the composition of the body and capsule caps: gelatin, iron dye yellow oxide, iron dye red oxide, titanium dioxide; in addition, in capsules at a dose of 160 mg - iron dye black oxide.

Pharmacological properties

The drug is characterized by antihypertensive properties.

Pharmacodynamics

Valsartan is an active, specific angiotensin II receptor antagonist intended for oral administration. It selectively blocks the AT 1 subtype receptors responsible for the effects of angiotensin II. As a result of this blockade, the concentration of angiotensin II in the blood plasma increases, which can lead to stimulation of unblocked AT 2 receptors. For valsartan, agonistic activity against AT 1 receptors of any severity is uncharacteristic. The affinity of this substance for AT 1 subtype receptors is approximately 20,000 times higher than for AT 2 subtype receptors.

The risk of coughing during treatment with the drug is very low, due to the lack of effect on the angiotensin-converting enzyme (ACE), which is responsible for the degradation of bradykinin. When comparing valsartan with an ACE inhibitor, it was found that the incidence of dry cough attacks was significantly lower in patients taking valsartan compared to patients taking an ACE inhibitor (2.6% and 7.9%, respectively). In the group of patients who previously had a dry cough during therapy with an ACE inhibitor, this complication was observed in 19.5% of cases when using valsartan, and in 19% of cases when using a thiazide diuretic, while in the group of patients who underwent a course therapy with an ACE inhibitor, cough was reported in 68.5% of cases.

Valsartan does not interact with and does not block ion channels or other hormone receptors that play an important role in the regulation of the cardiovascular system. Treatment with this drug in patients with arterial hypertension is accompanied by a decrease in blood pressure, which does not lead to a change in heart rate.

After oral administration of a single dose of valsartan in most patients, the antihypertensive effect is recorded within 2 hours, and the peak decrease in blood pressure is observed after about 4-6 hours. After taking the drug, the antihypertensive effect persists for about 24 hours. With repeated appointment of valsartan, the maximum reduction in blood pressure, regardless of the dose taken, is achieved on average within 2-4 weeks and remains at the achieved level during a long course of therapy. When this drug is combined with hydrochlorothiazide, there is an additional decrease in blood pressure, confirmed by reliable clinical data. Sudden withdrawal of valsartan does not lead to a sharp increase in blood pressure or other undesirable consequences.

The mechanism of action of the drug in chronic heart failure lies in its ability to eliminate the negative consequences of chronic hyperactivation of the renin-angiotensin-aldosterone system (RAAS) and its main effector, angiotensin II. These include vasoconstriction, stimulation of excessive synthesis of hormones that have a synergistic effect with respect to the RAAS (endothelin, catecholamines, vasopressin, aldosterone, etc.), cell proliferation, which causes remodeling of target organs (kidneys, blood vessels, heart), fluid retention in the body . In patients with chronic heart failure, while taking valsartan, cardiac output increases, diastolic pressure in the pulmonary artery and wedge pressure in the pulmonary capillaries decrease, and preload decreases. The use of the drug is not only accompanied by hemodynamic effects, but also reduces the retention of water and sodium in the body due to mediated blockade of aldosterone production.

It has been proven that valsartan does not significantly affect the level of uric acid, total cholesterol, and when conducting a fasting study - on the level of glucose and triglycerides in the blood serum.

Pharmacokinetics

After oral administration, valsartan is absorbed at a high rate, but the degree of absorption can vary widely. On average, the absolute bioavailability of this substance reaches 23%. Its maximum concentration in blood plasma is recorded after 2 hours. With regular use of valsartan, the maximum decrease in blood pressure is observed after 4 weeks. With a single dose of the drug during the day, valsartan accumulates slightly. Its content in blood plasma is the same in women and men.

Valsartan shows a high activity of binding to plasma proteins (94-97%), mainly to albumin. Its volume of distribution is small and is approximately 17 liters. Plasma clearance is relatively low (about 2 L/hour) compared to hepatic blood flow (about 30 L/hour).

The metabolism of valsartan is not very pronounced (about 20% of the dose taken passes into the form of metabolites). In blood plasma, a hydroxyl metabolite is determined in small concentrations [its AUC (area under the concentration-time curve) is less than 10% of that for valsartan]. This metabolite has no pharmacological activity. Valsartan has a biphasic elimination from the body: the half-life for the alpha phase is less than 1 hour, and for the beta phase it is approximately 9 hours.

Valsartan is excreted mainly unchanged in the faeces (approximately 83% of the administered dose) and in the urine (approximately 13% of the administered dose).

The intake of valsartan with food leads to a decrease in AUC by approximately 48%. However, 8 hours after the drug enters the body, the concentration of the active substance in the blood plasma, taken on an empty stomach and with food, is the same. The decrease in AUC is not accompanied by a clinically significant decrease in the therapeutic effect of valsartan, so the drug can be taken both before and after meals.

In patients with chronic heart failure, the time to reach maximum concentration and half-life are identical to those in healthy volunteers. The increase in the maximum concentration and AUC is directly proportional to the increase in the dose of the drug (during the experiment, it increased from 40 to 160 mg taken 2 times a day). The average cumulation factor is 1.7. When taken orally in such patients, the clearance of valsartan reached approximately 4.4 l / h, while the age of the patients did not affect its value.

In some patients over the age of 65, the systemic bioavailability of the drug is higher than that in young patients, but this fact is not of particular clinical significance.

No correlation was found between renal function and systemic bioavailability of the drug. In patients with renal dysfunction and CC more than 10 ml / min, there is no need for dose adjustment of valsartan. To date, studies of the use of the drug in patients on hemodialysis have not been conducted. Valsartan has a high degree of binding to plasma proteins, so its removal by hemodialysis is almost impossible.

In patients with mild to moderate liver dysfunction, the bioavailability of valsartan is increased by 2 times compared with healthy volunteers. However, the AUC values ​​of this substance do not correlate with the degree of hepatic impairment. The use of the drug in patients with severe liver dysfunction has not been studied.

Indications for use

• chronic heart failure (as part of standard therapy with the use of cardiac glycosides, diuretics, angiotensin-converting enzyme inhibitors or beta-blockers);
• arterial hypertension.

In addition, to increase survival, Valsartan is prescribed to patients with stable hemodynamic parameters after acute myocardial infarction complicated by left ventricular systolic dysfunction and / or left ventricular failure.

Contraindications

• age up to 18 years;
• severe form (above 9 points on the Child-Pugh scale) of liver dysfunction, cholestasis, biliary cirrhosis of the liver;
• concomitant therapy with angiotensin II receptor antagonists or ACE inhibitors (angiotensin-converting enzyme) with aliskiren in patients with diabetes mellitus;
• the period of pregnancy planning and childbearing;
• breast-feeding;
• individual hypersensitivity to the components of the drug.

According to the instructions, Valsartan should be used with caution in patients who limit salt intake, with bilateral renal artery stenosis, stenosis of the artery of a single kidney, after kidney transplantation, with renal failure [creatinine clearance (CC) less than 10 ml / min], hemodialysis, primary hyperaldosteronism , reduced volume of circulating blood (CBV) (including conditions with diarrhea and vomiting), liver failure of non-biliary genesis of mild to moderate severity (without cholestasis), hypertrophic obstructive cardiomyopathy, chronic heart failure II-IV functional class according to the NYHA classification, mitral or aortic stenosis.

Instructions for use Valsartan: method and dosage

Film-coated tablets

Tablets are taken orally, swallowed whole and washed down with water.

• chronic heart failure: initial dose - 40 mg 2 times a day. Within 14 days, taking into account the individual tolerability of the drug, a single dose should be gradually increased to 80 mg or 160 mg. This may require a reduction in the dose of concomitantly used diuretics. The maximum daily dose is 320 mg;
• arterial hypertension: the initial dose is 80 mg 1 time per day. In the absence of the desired therapeutic effect after 14-28 days of therapy, the daily dose can be increased to 320 mg or an additional intake of diuretics can be prescribed.

To improve survival after myocardial infarction, the use of Valsartan should be started within the first 12 hours, taking 20 mg 2 times a day. Over the next 14 days, the dose is gradually increased by titration, taking 40 mg, then 80 mg 2 times a day. By the end of the third month of therapy, it is recommended to reach the target dose of 320 mg per day, taking 160 mg 2 times a day. When increasing the dose, it is necessary to take into account the tolerability of the drug by the patient.

In case of impaired renal function or in elderly patients, dose adjustment is not required.

In mild or moderate liver dysfunction of non-biliary genesis without cholestasis, the dose of the drug should not exceed 80 mg per day.

Capsules

The capsules are intended for oral administration.

Side effects

• digestive system: nausea, diarrhea, increased bilirubin levels;
• cardiovascular system: postural hypotension, postural dizziness, arterial hypotension;
• hematopoietic system: decreased hemoglobin and hematocrit levels, neutropenia;
• nervous system: headache, dizziness;
• metabolism: hyperkalemia;
• urinary system: rarely - a functional disorder of the kidneys, an increase in the level of urea nitrogen and creatinine (especially in patients with chronic heart failure);
• allergic reactions: rarely - itching, rash, serum sickness, angioedema, vasculitis;
• other: general weakness, fatigue, cough, increased risk of viral infections, pharyngitis.

Overdose

The main symptom of an overdose of Valsartan is a pronounced decrease in blood pressure, which can later lead to clouding of consciousness, shock and / or collapse. In this case, symptomatic therapy is recommended, the features of which depend on the severity of the symptoms and the time elapsed since the drug was taken. In case of accidental overdose, vomiting should be provoked (if Valsartan has been taken recently) or gastric lavage should be performed. With a pronounced decrease in blood pressure, according to the protocols, it is necessary to inject a 0.9% solution of sodium chloride intravenously and lay the patient down, placing his legs in an elevated position, for a period of time sufficient for therapy. Active measures are also being taken to restore the full functioning of the cardiovascular system, including regular monitoring of the amount of urine excreted, the volume of circulating blood, and the activity of the heart and respiratory system.

special instructions

With a reduced content of BCC and / or sodium, the use of Valsartan should be started after the restoration of their level in the body, if necessary, then reduce the dose of the diuretic. This will avoid clinical manifestations of arterial hypotension, which rarely occur at the beginning of treatment.

With caution, it is recommended to combine with potassium-containing dietary supplements and salt substitutes, potassium-sparing diuretics, heparin or other agents that may contribute to the development of hyperkalemia.

With unilateral or bilateral stenosis of the renal artery, regular monitoring of the level of creatinine and urea concentrations in the blood serum is required.

The combination of the drug or ACE inhibitors with aliskiren should be avoided in severe renal impairment (CC less than 30 ml / min).

In the treatment of patients with biliary tract obstruction, the clearance of valsartan is reduced.

Patients in whom Valsartan caused Quincke's edema, drug therapy is canceled with a ban on resuming its intake.

In arterial hypertension in patients with primary hyperaldosteronism, the use of the drug has no therapeutic effect.

Due to the risk of a significant hypotensive effect of the drug at the beginning of therapy in patients with chronic heart failure or myocardial infarction, it is necessary to regularly monitor blood pressure (BP).

There is a risk of developing oliguria and / or worsening azotemia, in rare cases, acute renal failure and / or death in chronic heart failure II-IV functional class (NYHA classification), therefore, these categories of patients should be periodically assessed for renal function.

In the treatment of arterial hypertension, in addition to monotherapy, the drug can be used in combination with acetylsalicylic acid, thrombolytics, beta-blockers and HMG-CoA reductase inhibitors (statins). It is not recommended to use simultaneously with ACE inhibitors, since monotherapy in this case has advantages.

In the combined therapy of chronic heart failure, the appointment of diuretics, cardiac glycosides, beta-blockers or ACE inhibitors is indicated. The use of a combination of ACE inhibitors, beta-blockers and Valsartan is not recommended.

Due to the risk of dizziness or fainting during the treatment period, care should be taken when driving vehicles and mechanisms.

Use during pregnancy and lactation

Reception of Valsartan during pregnancy is strictly contraindicated. The risk to the fetus in this case is quite significant, due to the mechanism of action of angiotensin II receptor antagonists. The impact of ACE inhibitors (drugs that affect the RAAS) on the fetus when they are prescribed in the II and III trimesters of pregnancy can lead to impaired development and intrauterine death. According to retrospective data, when taking ACE inhibitors in the first trimester of pregnancy, the risk of having children with intrauterine malformations increases. There is information about kidney dysfunction, oligohydramnios in newborns and spontaneous abortions in mothers who accidentally received valsartan during pregnancy. This drug should also not be used in women planning a pregnancy. In this case, the doctor should inform women of reproductive age about the possible risk of a negative effect of valsartan on the fetus during pregnancy.

If pregnancy occurs during treatment with Valsartan, it should be canceled as soon as possible. There is no information on the penetration of the drug into breast milk, so taking the drug is contraindicated during breastfeeding.

Application in childhood

The efficacy and safety of the drug in children have not been proven.

For impaired renal function

There are no data on the safety of taking Valsartan in patients with CC less than 10 ml / min. Since inhibition of the RAAS is observed in predisposed patients, it may be accompanied by changes in kidney function.

drug interaction

With the simultaneous use of Valsartan:

• agents acting on the renin-angiotensin-aldosterone system (RAAS) have an effect on increasing the incidence of renal dysfunction, arterial hypotension and hyperkalemia compared with monotherapy;
• atenolol, warfarin, cimetidine, furosemide, digoxin, indomethacin, amlodipine, hydrochlorothiazide, glibenclamide do not cause a clinically significant interaction;
• non-steroidal anti-inflammatory drugs, including selective cyclooxygenase-2 inhibitors, can reduce the antihypertensive effect of valsartan, cause an increase in plasma potassium and worsen kidney function;
• lithium preparations enhance their toxic effect by increasing the content of lithium in the blood plasma;
• potassium preparations, potassium-sparing diuretics (including amiloride, spironolactone, triamterene), potassium-containing salts can increase the level of potassium concentration in the blood serum, and in heart failure - the content of creatinine in the blood serum;
• rifampicin, cyclosporine, ritonavir may increase the concentration of valsartan in the blood serum.

Analogues

The analogues of Valsartan are: Valz, Diovan, Valsakor, Valsartan Zentiva.

Terms and conditions of storage

Keep away from children.

Store at temperatures up to 25 ° C in a place protected from light.

Shelf life - 3 years.

For one tablet:

Round biconvex tablets, film-coated light pink in color, two layers are visible on the break - a white or almost white core and a film shell. Tablets with a dosage of 40 and 80 mg with a risk on one side.

Valsartan is an active specific angiotensin II receptor antagonist intended for oral administration. Selectively blocks AT 1 subtype receptors, which are responsible for the effects of angiotensin II. The consequence of the blockade of AT 1 receptors is an increase in the plasma concentration of angiotensin II, which can stimulate unblocked AT 2 receptors. does not have any pronounced agonistic activity against AT 1 receptors. The affinity of valsartan for AT 1 subtype receptors is approximately 20,000 times higher than for AT 2 subtype receptors.

The likelihood of coughing when using valsartan is very low, due to the lack of influence on the angiotensin-converting enzyme (ACE), which is responsible for the degradation of bradykinin. Comparison of valsartan with an ACE inhibitor showed that the incidence of dry cough was significantly (p< 0,05) ниже у пациентов, получавших , чем у пациентов, получавших ингибитор АПФ (2,6% против 7,9% соответственно). В группе пациентов, у которых ранее при лечении ингибитором АПФ развивался сухой кашель, при лечении валсартаном это осложнение было отмечено в 19,5% случаев, а при лечении тиазидным диуретиком - в 19,0% случаев, в то время как в группе пациентов, получавших лечение ингибитором АПФ, кашель наблюдался в 68,5% случаев (р < 0,05). не вступает во взаимодействие и не блокирует рецепторы других гормонов или ионные каналы, имеющие важное значение для регуляции функций сердечно-сосудистой системы. При лечении валсартаном пациентов с артериальной гипертензией отмечается снижение артериального давления (АД), не сопровождающееся изменением частоты сердечных сокращений (ЧСС).

After ingestion of a single dose of the drug in most patients, the onset of antihypertensive action is noted within 2 hours, and the maximum decrease in blood pressure is achieved within 4-6 hours. After taking the drug, the antihypertensive effect persists for more than 24 hours. With repeated appointments of the drug, the maximum reduction in blood pressure, regardless of the dose taken, is usually achieved within 2-4 weeks and is maintained at the achieved level during long-term therapy. In the case of a combination of the drug with hydrochlorothiazide, a significant additional decrease in blood pressure is achieved. Abrupt discontinuation of valsartan is not accompanied by a sharp increase in blood pressure or other undesirable consequences.

The mechanism of action of valsartan in chronic heart failure is based on its ability to eliminate the negative effects of chronic hyperactivation of the renin-angiotensin-aldosterone system (RAAS) and its main effector, angiotensin II, namely, vasoconstriction; fluid retention in the body; cell proliferation leading to remodeling of target organs (heart, kidneys, blood vessels); stimulation of excessive synthesis of hormones that act synergistically with the RAAS (catecholamins, aldosterone, vasopressin, endothelin, etc.). Against the background of the use of valsartan in chronic heart failure (CHF), preload decreases, wedge pressure in the pulmonary capillaries (PCWP) and diastolic pressure in the pulmonary artery decrease, and cardiac output increases. Along with hemodynamic effects, due to the mediated blockade of aldosterone synthesis, it reduces the retention of sodium and water in the body.

It was found that the drug did not have a significant effect on the concentration of total cholesterol, uric acid, as well as in the study on an empty stomach - on the concentration of triglycerides and glucose in the blood serum.

Valsartan is rapidly absorbed after oral administration, but the degree of absorption varies widely. The average absolute bioavailability of valsartan is 23%. The time required to reach the maximum concentration (TC m ah) - 2 hours. After regular use, the maximum decrease in blood pressure develops after 4 weeks. When using the drug once a day, its cumulation is insignificant. The plasma concentration of valsartan is the same in men and women.

Valsartan is actively associated with serum proteins (94-97%), mainly with albumin. The volume of distribution of valsartan is small, about 17 liters. Plasma clearance is relatively low (approximately 2 l/hour) when compared with hepatic blood flow (approximately 30 l/hour).

Valsartan is not extensively metabolized (about 20% of the dose taken is determined as metabolites). The hydroxyl metabolite is determined in plasma at low concentrations (less than 10% of the area under the concentration-time curve (AUC) of valsartan). This metabolite is pharmacologically inactive. It is excreted in two phases: an alpha phase with a half-life of less than 1 hour and a beta phase with a half-life of about 9 hours.

Non-steroidal anti-inflammatory drugs (NSAIDs): with simultaneous use with NSAIDs (including selective inhibitors of cyclooxygenase-2 (COX-2)) may reduce the antihypertensive effect of valsartan. When using angiotensin II receptor antagonists simultaneously with NSAIDs, it is possible to worsen kidney function and increase the content of potassium in the blood plasma. If necessary, the simultaneous use of valsartan and NSAIDs before the start of therapy, it is necessary to assess the function of the kidneys and correct violations of the water and electrolyte balance.

Lithium preparations: with the simultaneous use of ACE inhibitors and angiotensin II receptor antagonists simultaneously with lithium preparations, an increase in the content of lithium in the blood plasma and an increase in its toxic effect are noted. it is not recommended to use simultaneously with lithium preparations (experience is limited). If necessary, the simultaneous use of the drug and lithium preparations, it is necessary to ensure the control of the content of lithium in the blood plasma.

Potassium preparations: the simultaneous use of potassium-sparing diuretics (including spironolactone, triamterene, amiloride), potassium preparations or salts containing potassium can lead to an increase in serum potassium and, in patients with heart failure, to an increase in serum creatinine concentration. If such combined treatment is deemed necessary, caution should be exercised.

Carrier proteins

According to the results of the study in vitro on liver cultures, it is a substrate for OATP1B1 and MRP 2 carrier proteins. Simultaneous administration of valsartan with inhibitors of the OATP1B1 carrier protein ( , ) and with an inhibitor of the MRP 2 carrier protein () can increase the systemic exposure of valsartan (C max and AUC).

Deficiency in the body of sodium and / or a decrease in circulating blood volume (BCC)

In patients with a severe deficiency in the body of sodium and / or reduced BCC, for example, those receiving high doses of diuretics, in rare cases, arterial hypotension, accompanied by clinical manifestations, may occur at the beginning of treatment with the drug. Before starting treatment with the drug, it is necessary to correct the content of sodium and / or BCC in the body, including by reducing the dose of the diuretic.

In the event of arterial hypotension, the patient should be laid down, legs elevated. If necessary, conduct an intravenous infusion of 0.9% sodium chloride solution. After the blood pressure stabilizes, treatment with the drug can be continued.

Hyperkalemia

When used simultaneously with dietary supplements containing potassium, potassium-sparing diuretics, potassium-containing salt substitutes, or with other drugs that can cause hyperkalemia (for example, heparin), care should be taken and regular monitoring of potassium levels in the blood should be carried out.

Renal artery stenosis

Use with caution in patients who drive vehicles and engage in activities that require increased attention and speed of motor and mental reactions (risk of dizziness or fainting).

Film-coated tablets, 40 mg, 80 mg and 160 mg.

7, 10, 14, 20, 28, 30, 56 tablets in a blister pack made of polyvinyl chloride film and printed lacquered aluminum foil.

7, 10, 14, 20, 28, 30, 40, 50 or 100 tablets in polymer jars for medicines.

One jar or 1, 2, 3, 4, 5, 6, 8 or 10 blister packs together with instructions for use are placed in a carton (pack).

In a place protected from light, at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Do not use after the expiration date.