Instructions for use VALSACOR® H160

Dosage form and composition

The medication is intended for oral administration and is available in the form of yellow film-coated tablets:

• Valsacor: contains the active substance valsartan - an antagonist of hormone receptors that provokes an increase in pressure in blood vessels, prevents the development of hypertensive attacks;
• Valsacor N80, ND160: a combination drug containing two active ingredients: valsartan and hydrochlorothiazide, has a more pronounced and long-lasting therapeutic effect, reduces blood pressure.

In addition to active compounds, pills contain auxiliary components: MCC, lactose, silicon dioxide, stabilizing and form-building additives.

Mechanism of action of drugs

Valsacor provides a long-term reduction in the resistance of vascular walls, prevents their spasms, improves myocardial contractility, and increases the volume of blood pumped by the heart. As a result, unfavorable symptoms of deficiency disappear:

• think in your ears and head;
• swelling;
• dyspnea;
• physical weakness;
• dizziness.

Valsacor N maintains normal blood pressure, reduces the likelihood of valsartan side effects, and helps hypertensive patients maintain good health. Hydrochlorothiazide in its composition has a diuretic effect, stimulates the excretion of excess sodium and chlorine.

The medicine quickly dissolves in the stomach after administration and is absorbed into the blood. The effect of one dose of tablets develops over 30–60 minutes, reaches a maximum after 4–5 hours and lasts up to a day. With regular use, Valsacor provides an increasing antihypertensive effect after 3-4 weeks - it prevents the development of high blood pressure.

About 60% of hydrochlorothiazide ingested interacts with blood proteins; in combination with valsartan, it is less bioavailable. The components of the drugs do not accumulate in the body. Metabolism occurs in the liver, then the remaining substances are excreted through the intestinal contents and through the kidneys. Disintegration and release occur approximately 9 hours after the dose of the drug.

Instructions for use VALSACOR® H160

Combined antihypertensive drug.

Valsartan/hydrochlorothiazide

In a double-blind, randomized, active-controlled study, patients who failed to achieve adequate BP control with hydrochlorothiazide 12.5 mg received a combination of valsartan/hydrochlorothiazide 160/12.5 mg had a decrease in mean BP (12.4/7.5 mmHg). ) compared with patients receiving only hydrochlorothiazide at a dose of 25 mg (5.2/2.1 mmHg). In addition, a greater number of patients (%) experienced a hypotensive effect on therapy with the combination of valsartan/hydrochlorothiazide 160/12.5 mg (diastolic blood pressure <140/90 mm Hg or a decrease in SBP ≥20 mm Hg or DBP ≥10 mm Hg .st.) (50%) compared to taking hydrochlorothiazide at a dose of 25 mg (25%).

In a double-blind, randomized, active-controlled study, patients who failed to achieve adequate BP control with valsartan 160 mg received a combination of valsartan/hydrochlorothiazide 160/12.5 mg had a decrease in mean BP (14.6/11.9 mmHg). ) compared with patients receiving only valsartan at a dose of 160 mg (8.7/8.8 mmHg). The difference in blood pressure reduction when comparing doses of 160/25 mg and 160/12.5 mg reached statistical significance. In addition, a greater number of patients (%) experienced a hypotensive effect (diastolic blood pressure <90 mmHg or decrease ≥10 mmHg) to therapy with the combination of valsartan/hydrochlorothiazide 160/25 mg (68%) and 160/ 12.5 mg compared to valsartan 160 mg (49%).

A double-blind, randomized, placebo-controlled, factorial design study compared different doses of valsartan/hydrochlorothiazide combinations with their respective components. When comparing placebo (1.9/4.1 mmHg), hydrochlorothiazide at a dose of 12.5 mg (7.3/7.2 mmHg), hydrochlorothiazide at a dose of 25 mg (12.7/9.3 mmHg) and valsartan at a dose of 160 mg (12.1/9.4 mmHg) the greatest decrease in mean blood pressure was observed when taking the combination of valsartan/hydrochlorothiazide 160/12.5 mg (17.8/13.5 mmHg) and 160/25 mg (22.5/15.3 mmHg) . In addition, a greater number of patients (%) experienced a hypotensive effect (diastolic blood pressure <90 mmHg or a decrease ≥10 mmHg) to therapy with the combination of valsartan/hydrochlorothiazide 160/12.5 mg (81%) and 160/ 12.5 mg (76%) compared with placebo (29%) and corresponding monotherapy with hydrochlorothiazide 12.5 mg (41%), 25 mg (54%), valsartan 160 mg (59%).

In controlled clinical studies of the combination of valsartan/hydrochlorothiazide, a dose-dependent decrease in serum potassium was observed. A decrease in serum potassium was observed more often in patients receiving hydrochlorothiazide at a dose of 25 mg than in patients receiving hydrochlorothiazide at a dose of 12.5 mg.

In controlled clinical trials of the valsartan/hydrochlorothiazide combination, the hypokalemic effect of hydrochlorothiazide was reduced as a result of the potassium-sparing effect of valsartan.

The beneficial effects of valsartan in combination with hydrochlorothiazide on cardiovascular mortality and morbidity are currently unknown. Epidemiological studies have shown that long-term treatment with hydrochlorothiazide reduces the risk of cardiovascular mortality and morbidity.

Valsartan

Valsartan is a selective angiotensin II receptor antagonist for oral administration. It has a selective antagonistic effect on receptors of the AT1 subtype. A consequence of AT1 receptor blockade is an increase in plasma concentrations of angiotensin II, which can stimulate unblocked AT2 receptors, which is believed to regulate the effects of AT1 receptors. Valsartan does not have agonist activity against AT1 receptors. Its affinity for receptors of the AT1 subtype is approximately 20,000 times greater than for receptors of the AT2 subtype. Valsartan does not interact with or block other hormone receptors or ion channels involved in regulating the function of the cardiovascular system.

Valsartan does not inhibit ACE, also known as kininase II, which converts angiotensin I to angiotensin II and destroys bradykinin. Due to the lack of influence on ACE, the effects of bradykinin and substance P are not potentiated, therefore, when taking angiotensin II receptor antagonists, the development of a dry cough is unlikely.

Clinical studies in which valsartan was compared with an ACE inhibitor showed that the incidence of dry cough was significantly lower in patients receiving valsartan compared to patients receiving an ACE inhibitor (2.6% versus 7.9%, respectively, p>0.05). In clinical trials in patients with a history of cough during ACE inhibitor therapy, dry cough was observed in 19.5% of patients switched to valsartan and 19% of patients treated with thiazide diuretics, compared with 68.5% of patients treated with an ACE inhibitor (p>0.05).

In the treatment of arterial hypertension, valsartan reduces blood pressure without affecting heart rate.

In most patients, after oral administration of a single dose of valsartan, the antihypertensive effect develops within 2 hours, and the maximum reduction in blood pressure is achieved within 4-6 hours. The antihypertensive effect of valsartan persists for 24 hours. With repeated prescriptions of valsartan, the maximum decrease in blood pressure is achieved, regardless of the dose , is achieved after 2-4 weeks and remains at the achieved level during long-term therapy. In combination with hydrochlorothiazide, a significant additional reduction in blood pressure is achieved.

Abrupt withdrawal of valsartan is not accompanied by rebound hypertension or other adverse clinical events.

During observations, it was revealed that as a result of the use of valsartan in patients with type 2 diabetes mellitus and microalbuminuria, protein excretion in the urine decreases. The MARVAL (Microalbuminuria Reduction with Valsartan) study assessed the reduction in urinary protein excretion with valsartan (80-160 mg once daily) compared with amlodipine (5-10 mg once daily) in 332 patients with type 2 diabetes mellitus (average age 58 years; 265 male patients) with microalbuminuria (valsartan - 58 mcg/min; amlodipine - 55.4 mcg/min), normal or elevated blood pressure and preserved renal function (blood creatinine <120 μmol/l) . At 24 weeks, urinary protein excretion decreased (p<0.001) by 42% (-24.2 μg/min; 95% CI:

• -40.4 to -19.1) when using valsartan and approximately 3% (-1.7 mcg/min;
• 95% CI: -5.5 to 14.9) with amlodipine, despite the same level of blood pressure reduction in both groups.

The DROP (The Diovan Reduction of Proteinuria) study continued to study the effectiveness of valsartan in reducing urinary protein excretion in 391 patients with arterial hypertension (BP 150/88 mm Hg) and type 2 diabetes mellitus, albuminuria (mean value - 102 µg/min; 20-700 µg/min) and preserved renal function (mean serum creatinine = 80 µmol/L). Patients were randomized to receive one of 3 doses of valsartan (160, 320, and 640 mg once daily) and were treated for 30 weeks. The purpose of the study was to establish the optimal dose of valsartan to reduce urinary protein excretion in hypertensive patients with type 2 diabetes mellitus. At 30 weeks, the percentage change in urinary protein excretion was significantly reduced by 36% from baseline with valsartan 160 mg (95% CI: 22 to 47%), with a 44% reduction with valsartan 320 mg. (95% CI:

• 31 to 54%). It was concluded that the use of valsartan 160-320 mg caused a clinically significant reduction in urinary protein excretion in patients with hypertension and type 2 diabetes mellitus.

Two large randomized controlled trials, ONTARGET (ONgoing Telmisartan Alone and incombination with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs Nephropathy in Diabetes), examined the use of ACE inhibitors in combination with angiotensin II receptor antagonists.

The ONTARGET study was conducted in patients with cardiovascular disease, cerebrovascular disease, or type 2 diabetes with evidence of end-organ damage.

The VA NEPHRON-D study was conducted in patients suffering from type 2 diabetes mellitus and diabetic nephropathy.

Compared with monotherapy, these studies did not show significant beneficial effects on renal function and/or cardiovascular outcomes and mortality, while an increased risk of hyperkalemia, acute renal failure and/or hypotension was observed. Due to similar pharmacodynamic properties, these results are relevant to other ACE inhibitors and angiotensin II receptor antagonists. Therefore, ACE inhibitors and angiotensin II receptor antagonists should not be used simultaneously in patients with diabetic nephropathy.

The ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease End points) study was designed to determine the benefits of adding aliskiren to standard ACE inhibitor or angiotensin II receptor antagonist therapy in patients with type 2 diabetes mellitus, chronic renal failure, cardiovascular diseases. The study was stopped early due to an increased risk of adverse outcomes. Stroke and cardiovascular mortality were observed more often in the aliskiren group than in the placebo group. Also, in the group taking aliskiren, undesirable side effects (hyperkalemia, hypotension, renal dysfunction) were more often observed.

Hydrochlorothiazide

Hydrochlorothiazide is a thiazide diuretic whose site of action is primarily in the distal renal tubules. In the renal cortex there are receptors that have high affinity and are the main binding site for thiazide diuretics, where the transport of NaCl into the distal tubules is suppressed. The mechanism of action of thiazides is due to inhibition of the cotransport of Na+ and Cl- ions, possibly due to competition for Cl- transport sites, which affects the mechanisms of electrolyte reabsorption:

• the excretion of sodium and chloride ions increases approximately equally in direct proportion. Indirectly, as a result of this diuretic effect, there is a decrease in plasma volume, resulting in increased renin activity, aldosterone secretion, and urinary excretion of potassium, resulting in a decrease in serum potassium concentration.

The relationship between renin and aldosterone is mediated by angiotensin II, therefore, with simultaneous use of valsartan, the decrease in serum potassium concentration is less pronounced than with the use of hydrochlorothiazide as monotherapy.

Non-melanoma skin cancer (NMSC)

Based on available data from epidemiological studies, there is a cumulative dose-dependent association between hydrochlorothiazide and NMSC. One study included a population of 71,533 cases of basal cell carcinoma and 8,629 cases of squamous cell carcinoma matched to 1,430,833 and 172,462 control populations, respectively. High-dose hydrochlorothiazide (cumulative ≥50,000 mg) was associated with an adjusted OR of 1.29 (95% CI: 1.23–1.35) for basal cell carcinoma and 3.98 (95% CI: 3.68–4.31) for squamous cell carcinoma. A clear dose-response relationship was observed for both basal cell carcinoma and squamous cell carcinoma. Another study showed a possible association between lip cancer (SCC) and HCTZ exposure: 633 cases of lip cancer were matched to 63,067 population controls using a risk-adjusted sampling strategy. A cumulative dose-response relationship was demonstrated with an adjusted OR of 2.1 (95% CI:

• 1.7-2.6), increasing to OR 3.9 (3.0-4.9) for the highest cumulative dose (~25,000 mg) and OR 7.7 (5.7-10.5) for the highest cumulative dose (~100,000 mg).

Valsacor: use according to instructions

The drug is taken as prescribed by a cardiologist for the following pathologies:

• heart failure of non-acute severity: with functional disorders while maintaining a stable physical condition and during periods of remission;
• after a heart attack, with persisting dysfunction of the left ventricle of the myocardium;
• chronic heart failure without correction of the condition with ACE inhibitors;

Valsacor N and ND are prescribed in cases of hypertension as part of complex treatment.

The treatment regimen depends on the existing health problems:

• average daily dosage at the initial stage: 20–40 mg of the drug twice a day;
• if necessary, the dose of the drug is increased to 160 mg per day;
• The maximum dose of medication per day is 320 mg.

The tablets are taken with a sufficient amount of water, regardless of meal time. There is no need to chew or crush the medicine beforehand. Valsacor is used for long-term correction of physical condition. The general course of its use is at least several months. If side effects are detected, the dose of the drug is reduced or it is recommended to buy a similar antihypertensive drug.

Valsacor 160 mg 90 pcs. film-coated tablets

pharmachologic effect

Angiotensin II receptor antagonist.

Composition and release form Valsacor 160 mg 90 pcs. film-coated tablets

Tablets - 1 tablet:

• Active ingredient: valsartan 160.00 mg;
• Excipients: lactose monohydrate 60.00 mg, microcrystalline cellulose 82.00 mg, povidone-K25 3.00 mg, croscarmellose sodium 4.00 mg, colloidal silicon dioxide 2.00 mg, magnesium stearate 9.00 mg;
• Film shell: hypromellose 6sr 5.52 mg, titanium dioxide (E171) 1.36 mg, iron dye yellow oxide (E172) 0.50 mg, iron dye red oxide (E172) 0.02 mg, macrogol-4000 0.60 mg.

7, 10, 14 or 15 tablets in a blister (blister pack) made of combined material PVC/PE/PVDC - aluminum foil.

2, 4, 8, 12, 14 or 20 blisters (blister packs) (7 tablets each), or 2, 3, 6 or 9 blisters (blister packs) (10 tablets), or 1.2 , 4, 6, 7 or 10 blisters (blister packs) (14 tablets each), or 2, 4 or 6 blisters (blister packs) (15 tablets each) together with instructions for use are placed in a cardboard pack.

Description of the dosage form

Oval, biconvex tablets with a score on one side, film-coated, brownish-yellow in color. Fracture appearance: white rough mass with a filmy brownish-yellow color.

Directions for use and doses

Inside, regardless of meal time.

Patients over 18 years of age

Arterial hypertension. The recommended starting dose of Valsacor® is 80 mg 1 time per day, regardless of the race, age and gender of the patient. The antihypertensive effect develops within 2 weeks and reaches its maximum after 4 weeks. In patients who fail to achieve adequate blood pressure control, the daily dose of valsartan may be gradually increased to a maximum daily dose of 320 mg.

In order to further reduce blood pressure, it is possible to use diuretics (hydrochlorothiazide), as well as the simultaneous use of other antihypertensive drugs.

CHF. The recommended starting dose of Valsacor® is 40 mg 2 times a day. The dose of the drug should be gradually increased over at least 2 weeks to 80 mg 2 times a day, and if well tolerated - up to 160 mg 2 times a day. The maximum daily dose is 320 mg in two doses. This may require a reduction in the dose of concomitantly taken diuretics.

Possible simultaneous use with other drugs intended for the treatment of CHF. However, simultaneous therapy with drugs of three classes: valsartan, ACE inhibitors and beta-blockers is not recommended.

Assessment of patients with CHF should include monitoring of renal function.

Use after acute myocardial infarction. Treatment should begin within 12 hours after the development of acute MI in the presence of stable hemodynamic parameters. After using an initial dose of 20 mg 2 times a day (1/2 tablet 40 mg), the dose of Valsacor® can be gradually increased by titration to: 40, 80 and 160 mg 2 times a day over several weeks. The maximum daily dose is 320 mg in 2 divided doses. It is recommended to increase the dose to 80 mg 2 times a day by the end of the 2nd week, and the maximum target dose of 160 mg 2 times a day can be achieved by the end of the 3rd month of therapy with Valsacor®. Achievement of the target dose depends on the tolerability of valsartan during the dose titration period.

If an excessive decrease in blood pressure develops, accompanied by clinical manifestations, or renal dysfunction, the dose of the drug should be reduced.

Possible simultaneous use with other drugs, incl. thrombolytic agents, acetylsalicylic acid as an antiplatelet agent, beta-blockers and HMG-CoA reductase inhibitors (statins). Concomitant use with ACE inhibitors is not recommended.

Assessment of patients' condition after acute MI should include monitoring of renal function.

Patients from 6 to 18 years old

AG. The recommended initial dose of Valsacor® in children and adolescents from 6 to 18 years of age is 40 mg for children weighing less than 35 kg and 80 mg for children weighing more than 35 kg. Dose adjustment is recommended taking into account the reduction in blood pressure. The maximum recommended daily doses are shown below.

With body weight ≥8 and

The use of higher doses is not recommended.

CHF and previous MI. The drug Valsacor® is not recommended for the treatment of CHF and post-acute myocardial infarction in patients under 18 years of age.

Elderly patients. No dose adjustment is required in patients over 65 years of age.

Renal dysfunction. No dose adjustment is required in patients with creatinine Cl more than 10 ml/min. The simultaneous use of Valsacor® with aliskiren in patients with moderate and severe renal impairment (creatinine Cl less than 60 ml/min) is contraindicated.

Liver dysfunction. In patients with mild or moderate liver dysfunction of non-biliary origin without cholestasis, the drug should be used with caution, the daily dose should not exceed 80 mg.

Patients with diabetes. The simultaneous use of Valsacor® with aliskiren in patients with diabetes is contraindicated.

Pharmacodynamics

Valsartan is a selective angiotensin II receptor antagonist (AT1 type) for oral administration, of a non-protein nature.

Selectively blocks AT1 receptors. The consequence of AT1 receptor blockade is an increase in the plasma concentration of angiotensin II, which can stimulate unblocked AT2 receptors, which balances the vasopressor effects associated with the stimulation of AT1 receptors. Valsartan does not have agonist activity against AT1 receptors. Its affinity for AT1 receptors is approximately 20,000 times higher than for AT2 receptors.

Valsartan does not inhibit ACE, also known as kininase II, which converts angiotensin I to angiotensin II and destroys bradykinin. Due to the lack of influence on ACE, the effects of bradykinin and substance P are not potentiated. The incidence of dry cough is lower in patients receiving angiotensin II receptor antagonists (ARA II) compared to patients receiving an ACE inhibitor. Valsartan does not interact with or block receptors of other hormones or ion channels involved in the regulation of cardiovascular functions.

Use for arterial hypertension in patients over 18 years of age

In the treatment of arterial hypertension (AH), valsartan reduces blood pressure without affecting heart rate.

After oral administration of a single dose of valsartan, the antihypertensive effect develops within 2 hours, and the maximum reduction in blood pressure is achieved within 4–6 hours. The antihypertensive effect of valsartan persists for 24 hours after its use. With continuous use of valsartan, the maximum reduction in blood pressure, regardless of the dose, is achieved after 2–4 weeks and is maintained at the achieved level during long-term therapy. Simultaneous use with hydrochlorothiazide allows achieving a significant additional reduction in blood pressure.

Sudden withdrawal of valsartan is not accompanied by a sharp increase in blood pressure or other undesirable clinical consequences (i.e., withdrawal syndrome does not develop). In patients with hypertension, diabetes mellitus (DM) type 2 and nephropathy, taking valsartan at a dose of 160–320 mg/day, a significant reduction in proteinuria (36–44%) was observed.

Use after acute myocardial infarction (MI) in patients over 18 years of age

When using valsartan for 2 years, starting from 12 hours to 10 days after the development of MI (complicated by left ventricular failure and/or left ventricular systolic dysfunction), overall mortality and cardiovascular mortality are reduced and the time to the first hospitalization for an exacerbation is extended. course of CHF, repeated MI, sudden cardiac arrest and stroke (without death).

CHF in patients over 18 years of age

When using valsartan (in an average daily dose of 254 mg) for 2 years in patients with CHF II–IV functional class according to the NYHA classification with a left ventricular ejection fraction (LVEF) less than 40% and an internal diastolic diameter of the LV more than 2.9 cm/m2 receiving standard therapy (ACE inhibitors, diuretics, digoxin, beta-blockers), there was a significant reduction in the risk of hospitalization due to exacerbation of CHF, a slowdown in the progression of CHF, an improvement in the functional class of CHF according to the NYHA classification, an increase in LVEF, as well as a decrease in the severity of cardiac symptoms failure and improved quality of life compared to placebo.

Use in patients over 18 years of age with hypertension and impaired glucose tolerance

When using valsartan and changing lifestyle, there was a statistically significant reduction in the risk of developing diabetes in patients with hypertension and impaired glucose tolerance. Valsartan had no effect on the incidence of deaths as a result of cardiovascular events, myocardial infarction and non-fatal transient ischemic attacks, the frequency of hospitalizations due to exacerbation of CHF or unstable angina, or arterial revascularization in this category of patients differing in age, gender and race accessories. In patients receiving valsartan, the risk of developing microalbuminuria was significantly lower than in patients not receiving this therapy.

The recommended starting dose of valsartan in patients with hypertension and impaired glucose tolerance is 80 mg once daily. If necessary, the dose can be increased to 160 mg.

Use in children and adolescents from 6 to 18 years of age with hypertension

In children and adolescents from 6 to 18 years of age, valsartan provides a dose-dependent gradual decrease in blood pressure. When using valsartan, the maximum reduction in blood pressure, regardless of the dose taken orally, is achieved within 2 weeks and is maintained at the achieved level during long-term therapy.

Pharmacokinetics

Suction. After taking valsartan orally, Cmax in blood plasma is achieved within 2–4 hours. The average absolute bioavailability is 23%. When using valsartan with food, AUC and Cmax in blood plasma are reduced by 40 and 50%, respectively. However, 8 hours after taking the drug, plasma concentrations of valsartan taken on an empty stomach and with food are the same. A decrease in AUC is not accompanied by a clinically significant decrease in the therapeutic effect of valsartan, so Valsacor® can be taken regardless of meal time.

Distribution. Vd of valsartan during the steady-state period after intravenous administration was about 17 l, which indicates the absence of a pronounced distribution of valsartan in tissues. Valsartan actively binds to plasma proteins (94–97%), mainly to albumin.

Metabolism. Valsartan does not undergo significant biotransformation; only about 20% of the dose taken orally is excreted in the form of metabolites. The hydroxyl metabolite is detected in blood plasma in low concentrations (less than 10% of the AUC of valsartan). This metabolite has no pharmacological activity.

Excretion. Valsartan is excreted in two phases: α-phase with T1/2α less than 1 hour and β-phase with T1/2β - about 9 hours. Valsartan is excreted mainly unchanged through the intestines (about 83%) and the kidneys (about 13%) . After intravenous administration, plasma clearance of valsartan is about 2 l/h, renal clearance is 0.62 l/h (about 30% of the total clearance). T1/2 of valsartan is 6 hours.

Pharmacokinetics of special groups of patients

Patients with CHF. In patients with CHF, the time to reach Cmax and T1/2 are similar to those in healthy volunteers. The increase in AUC and Cmax is directly proportional to the increase in the dose of valsartan (from 40 to 160 mg 2 times a day). The cumulation factor is, on average, 1.7. When taken orally, the clearance of valsartan is about 4.5 l/h. The age of patients with CHF did not affect the clearance of valsartan.

Elderly patients (over 65 years old). In some patients over 65 years of age, the bioavailability of valsartan was higher than in younger patients, which is not clinically significant.

Patients with impaired renal function. The renal clearance of valsartan is only 30% of the total clearance, therefore there is no correlation between renal function and systemic bioavailability of valsartan. No dose adjustment is required in patients with impaired renal function (creatinine Cl more than 10 ml/min). The safety of valsartan in patients with creatinine Cl less than 10 ml/min and patients on hemodialysis has not been established, so the drug should be used with caution in such patients. Since the degree of binding of valsartan to plasma proteins is high, its elimination during hemodialysis is unlikely.

Patients with impaired liver function. About 70% of the absorbed dose of valsartan is excreted through the intestines, mainly unchanged. Valsartan is not significantly metabolized. In patients with mild or moderate hepatic impairment, the AUC of valsartan increased by 2 times compared to that in healthy volunteers. However, there is no correlation between valsartan AUC values ​​and the degree of liver dysfunction. The use of valsartan in patients with severe hepatic impairment has not been studied.

Patients from 6 to 18 years old. The pharmacokinetics of valsartan in children and adolescents from 6 to 18 years of age does not differ from the pharmacokinetics of valsartan in patients over 18 years of age.

Indications for use Valsacor 160 mg 90 pcs. film-coated tablets

Patients over 18 years of age

• arterial hypertension.
• chronic heart failure (II–IV functional class according to the NYHA classification) as part of complex therapy (against the background of standard therapy) in patients not receiving ACE inhibitors;
• increasing the survival rate of patients after acute MI complicated by left ventricular failure and/or left ventricular (LV) systolic dysfunction in the presence of stable hemodynamic parameters.

Patients from 6 to 18 years old

• arterial hypertension in children and adolescents from 6 to 18 years.

Contraindications

• hypersensitivity to valsartan or other components of the drug;
• severe liver dysfunction (more than 9 points on the Child-Pugh scale), biliary cirrhosis and cholestasis;
• simultaneous use with aliskiren in patients with diabetes mellitus or moderate to severe renal impairment (creatinine clearance less than 60 ml/min);
• lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome, since Valsacor® contains lactose;
• pregnancy;
• breastfeeding period;
• age up to 6 years - according to arterial hypertension, up to 18 years - according to other indications.

With caution: hyperkalemia; simultaneous use of potassium-sparing diuretics; potassium preparations; potassium-containing dietary supplements or other drugs that can increase the level of potassium in the blood plasma (for example, heparin); mild and moderate liver dysfunction of non-biliary origin without cholestasis; severe renal dysfunction (creatinine Cl less than 10 ml/min - no clinical data), renal dysfunction in patients from 6 to 18 years (creatinine Cl less than 30 ml/min), incl. those on hemodialysis, hyponatremia, following a diet with limited salt intake, conditions accompanied by a decrease in blood volume (including diarrhea, vomiting); bilateral renal artery stenosis or stenosis of the artery of a single kidney; condition after kidney transplantation; primary hyperaldosteronism, in patients with chronic heart failure of functional class III–IV (according to NYNA); whose kidney function depends on the state of the RAAS; stenosis of the aortic and/or mitral valve; hypertrophic obstructive cardiomyopathy (HOCM), in patients with hereditary angioedema or angioedema during previous therapy with ARB II or ACE inhibitors.

It is not recommended to use ARB II, including valsartan, concomitantly with ACE inhibitors, since their simultaneous use does not have advantages over valsartan or ACE inhibitor monotherapy in terms of overall mortality.

Application of Valsacor 160 mg 90 pcs. film-coated tablets during pregnancy and breastfeeding

The use of ARA II in the first trimester of pregnancy is not recommended. The use of ARA II is contraindicated in the II–III trimesters of pregnancy, since use in the II–III trimesters of pregnancy can cause fetotoxic effects (decreased renal function, oligohydramnios, delayed ossification of fetal skull bones) and neonatal toxic effects (renal failure, arterial hypotension, hyperkalemia).

If, nevertheless, the drug was used in the II–III trimesters of pregnancy, then it is necessary to conduct an ultrasound of the kidneys and bones of the fetal skull.

When planning pregnancy, it is recommended that the patient be transferred to alternative antihypertensive therapy, taking into account the safety profile. If pregnancy is confirmed, Valsacor® should be discontinued as soon as possible.

Newborns whose mothers received ARA II during pregnancy require medical supervision because there is a risk of developing arterial hypotension. There is no data on the excretion of valsartan into breast milk. Therefore, the issue of stopping breastfeeding or canceling valsartan therapy and switching to alternative antihypertensive therapy should be decided, taking into account the safety profile.

special instructions

Hyperkalemia. Caution should be exercised when using potassium-sparing diuretics (spironolactone, eplerenone, triamterene, amiloride), potassium supplements, potassium-containing salt substitutes or other drugs that can increase plasma potassium levels (for example, heparin). It is necessary to regularly monitor the potassium content in the blood plasma.

Renal dysfunction. In patients with impaired renal function, no dose changes are required. Because There are no data on the use of the drug in severe renal failure (creatinine Cl less than 10 ml/min or 0.167 ml/s) and in patients on hemodialysis; in such cases, the drug is recommended to be used with caution.

The simultaneous use of valsartan with aliskiren in patients with moderate and severe renal impairment (creatinine clearance less than 60 ml/min) is contraindicated.

Liver dysfunction. In patients with mild to moderate liver dysfunction without cholestasis, Valsacor® should be used with caution.

Patients with hyponatremia and/or dehydration. In patients with severe hyponatremia and/or dehydration, for example due to taking large doses of diuretics, in rare cases, arterial hypotension with clinical manifestations may develop at the beginning of therapy with Valsacor®. Before starting treatment, it is recommended to restore sodium and/or bcc levels, in particular by reducing the doses of diuretics.

Renal artery stenosis. The use of valsartan in a short course in patients with renovascular hypertension, which developed secondary to stenosis of the artery of a single kidney, does not cause significant changes in renal hemodynamics, creatinine concentration or urea nitrogen in the blood serum. However, given that other drugs that affect the RAAS may cause an increase in serum urea and creatinine concentrations in patients with bilateral renal artery stenosis or arterial stenosis of a solitary kidney, it is necessary to regularly monitor the concentrations of creatinine and residual urea nitrogen in the blood serum.

Condition after kidney transplantation. The safety of using Valsacor® in patients who have recently undergone kidney transplantation has not been established.

Primary hyperaldosteronism. Patients with primary hyperaldosteronism are resistant to antihypertensive drugs that affect the RAAS, therefore the use of Valsacor® is not recommended for such patients.

Stenosis of the aortic and/or mitral valves, HOCM. The drug Valsacor® should be used with caution in patients with hemodynamically significant stenosis of the aortic and/or mitral valves or with HOCM.

The period after an MI. Concomitant use with ACE inhibitors is not recommended, because has no additional clinical benefits over monotherapy and increases the risk of adverse events.

The use of valsartan in patients after a myocardial infarction often leads to a slight decrease in blood pressure, but discontinuation of therapy due to arterial hypotension is usually not required if drug dosage recommendations are followed.

Treatment with Valsacor® should be initiated cautiously. Assessment of the condition of patients after acute myocardial infarction should include monitoring of renal function.

Possible simultaneous use in acute MI with other drugs: thrombolytics, acetylsalicylic acid, beta-blockers and HMG-CoA reductase inhibitors (statins).

CHF. In patients with CHF, the simultaneous use of three classes of drugs is not recommended: ACE inhibitors, beta-blockers and valsartan, because this therapy did not provide additional clinical effect, and the risk of adverse events increased. Use in patients with CHF is usually accompanied by a decrease in blood pressure, however, if recommendations for dose selection are followed, treatment rarely requires discontinuation due to arterial hypotension. Treatment with Valsacor® in patients with CHF should be initiated with caution. Due to the suppression of RAAS activity in some patients (for example, in patients with CHF III–IV functional class according to the NYNA classification, whose kidney function depends on the state of the RAAS) during therapy with ACE inhibitors, a change in renal function is possible: the development of oliguria and/or progressive azotemia, and in in rare cases - acute renal failure and/or death. The drug Valsacor® blocks angiotensin II receptors, so patients with CHF require regular monitoring of renal function.

History of angioedema. Among patients with angioedema during therapy with Valsacor®, there were cases of a history of angioedema, incl. and ACE inhibitors. If angioedema develops, the drug should be discontinued immediately and the possibility of repeated use should be excluded.

Special information on excipients

The drug Valsacor® contains lactose, so it should not be used for the following conditions: lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Impact on the ability to perform potentially hazardous activities that require special attention and quick reactions (for example, driving, working with moving mechanisms). Due to the possibility of dizziness or weakness while using the drug Valsacor®, care must be taken when driving vehicles and engaging in potentially hazardous activities.

Overdose

Symptoms: the main expected manifestation of a valsartan overdose is a pronounced decrease in blood pressure, which can lead to impaired consciousness, collapse and/or shock.

Treatment: symptomatic, it is recommended to induce vomiting and rinse the stomach. If a pronounced decrease in blood pressure develops, it is necessary to transfer the patient to a supine position with his legs raised up, and administer a 0.9% sodium chloride solution intravenously. Regular monitoring of the activity of the heart and respiratory system, blood volume and the amount of urine excreted is recommended. Hemodialysis is ineffective.

Side effects Valsacor 160 mg 90 pcs. film-coated tablets

Classification of the frequency of side effects of the World Health Organization (WHO): very often - ≥1/10; often - from ≥1/100 to

The safety profile of valsartan in patients with hypertension aged 6 to 18 years does not differ from the safety profile of valsartan in patients with hypertension over 18 years of age.

Arterial hypertension

From the blood and lymphatic system: frequency unknown - decreased hemoglobin, decreased hematocrit, neutropenia, thrombocytopenia.

From the immune system: frequency unknown - hypersensitivity reactions, including serum sickness.

Metabolism and nutrition: frequency unknown - increased potassium levels in the blood serum, hyponatremia.

From the organ of hearing and labyrinthine disorders: infrequently - vertigo.

From the side of blood vessels: frequency unknown - vasculitis.

From the respiratory system, chest and mediastinal organs: infrequently - cough.

From the gastrointestinal tract: infrequently - abdominal pain.

From the liver and biliary tract: frequency unknown - impaired liver function, including increased concentration of bilirubin in the blood plasma.

From the skin and subcutaneous tissues: frequency unknown - angioedema, skin rash, itching, bullous dermatitis.

Musculoskeletal and connective tissue disorders: frequency unknown - myalgia.

From the kidneys and urinary tract: frequency unknown - impaired renal function and renal failure, increased concentration of creatinine in the blood serum.

General disorders and disorders at the injection site: uncommon - increased fatigue.

During clinical studies in patients with hypertension, the following adverse events were observed, the cause-and-effect relationship of which with valsartan was not established: arthralgia, asthenia, back pain, diarrhea, dizziness, insomnia, decreased libido, nausea, peripheral edema, pharyngitis, rhinitis, sinusitis, upper respiratory tract infections.

After acute MI and/or chronic heart failure (II–IV functional class according to the NYHA classification)

From the blood and lymphatic system: frequency unknown - thrombocytopenia.

From the immune system: frequency unknown - hypersensitivity reactions, including serum sickness.

From the side of metabolism and nutrition: infrequently - hyperkalemia; frequency unknown - increased potassium content in the blood serum, hyponatremia.

From the nervous system: often - dizziness, postural dizziness; infrequently - fainting, headache.

From the organ of hearing and labyrinthine disorders: infrequently - vertigo.

From the heart: infrequently - increased symptoms of CHF.

Vascular disorders: often - marked decrease in blood pressure, orthostatic hypotension; frequency unknown - vasculitis.

From the respiratory system, chest and mediastinal organs: infrequently - cough.

From the gastrointestinal tract: infrequently - nausea, diarrhea.

From the liver and biliary tract: frequency unknown - impaired liver function.

From the skin and subcutaneous tissues: infrequently - angioedema; frequency unknown - skin rash, skin itching, bullous dermatitis.

From the musculoskeletal and connective tissue side: rarely - rhabdomyolysis; frequency unknown - myalgia.

From the kidneys and urinary tract: often - impaired renal function and renal failure; uncommon - acute renal failure, increased serum creatinine concentration; frequency unknown - increased urea nitrogen content in the blood plasma.

General disorders and disorders at the injection site: infrequently - asthenia, increased fatigue.

Drug interactions

Concomitant use is contraindicated

Concomitant use of ARB II, including valsartan, or ACE inhibitors with aliskiren is contraindicated in patients with diabetes or moderate to severe renal impairment (creatinine clearance less than 60 ml/min).

Concomitant use is not recommended

Lithium. Simultaneous use with lithium preparations is not recommended, because a reversible increase in the concentration of lithium in the blood plasma and an increase in its toxic effect are possible. The risk of toxic effects associated with the use of lithium preparations may further increase when used simultaneously with Valsacor® and diuretics. If simultaneous use with lithium preparations is necessary, the concentration of lithium in the blood plasma should be carefully monitored.

Potassium-sparing diuretics (spironolactone, eplerenone, triamterene, amiloride), potassium supplements, potassium-containing nutritional supplements and other drugs and substances that can cause hyperkalemia (for example, heparin). If simultaneous use with drugs that affect potassium levels is necessary, it is recommended to monitor the potassium content in the blood plasma.

Concomitant use with caution

Double blockade of the RAAS. In some patients, double blockade of the RAAS was accompanied by the development of arterial hypotension, syncope, hyperkalemia and renal dysfunction (including acute renal failure (ARF). Caution is required when using ARB II, including valsartan, with drugs that affect the RAAS, such as inhibitors ACE or aliskiren.

NSAIDs, incl. selective COX-2 inhibitors, acetylsalicylic acid in a dose of more than 3 g/day and non-selective NSAIDs. When used simultaneously with valsartan, it is possible to reduce the antihypertensive effect, increase the risk of developing renal dysfunction and increase the potassium content in the blood plasma. Before starting combination therapy, it is recommended to evaluate renal function, as well as correct water and electrolyte imbalances.

Transport proteins. In vitro studies in liver cultures have shown that valsartan is a substrate for the transporter proteins OATP1B1/OATP1B3 and MRP2. Concomitant use of valsartan with inhibitors of the OATP1B1/OATP1B3 transport protein (rifampicin, cyclosporine) or MRP2 (ritonavir) may increase the systemic exposure of valsartan (Cmax and AUC). Caution must be exercised when starting simultaneous use with the above drugs or after their discontinuation.

No drug interactions

No clinically significant interactions were identified with the following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine and glibenclamide.

Patients from 6 to 18 years old. In children and adolescents, hypertension is often associated with impaired renal function. The simultaneous use of valsartan with other drugs that affect the RAAS may cause an increase in potassium levels in the blood plasma in such patients. Caution should be exercised when using the above combination simultaneously and regular monitoring of renal function and plasma potassium levels in this group of patients.

Side effects

During treatment with Valsacor, the following are likely:

• severe hypotension;
• muscle weakness, drowsiness, fatigue;
• loss of appetite, nausea, impaired intestinal motility;
• back pain;
• cough;
• insomnia.

In case of overdose, vomiting, disturbances in heart rhythm, coordination of movements, water-salt balance develop, a sharp headache occurs, a feeling of stunnedness, fainting, and toxic shock are possible.

Precautions and contraindications

Valsacor requires careful use and constant monitoring of well-being in cases of impaired renal and liver function during treatment after a heart attack. The drug enhances the toxic effect of medications containing acetylsalicylic acid. It is not advisable to take Valsacor simultaneously with cardiac glycosides, anti-gout medications, or potassium-sparing agents.

When combined with barbiturates, adrenergic blockers, vasodilators, the diuretic and hypotensive effect of Valsacor is enhanced. It is important to remember this when choosing dosages.

The medicine affects psychomotor reactions, so during the treatment period caution is required when creating vehicles and operating special equipment.

The drug is incompatible with alcohol and can provoke a sharp drop in blood pressure, hypoxia and vascular collapse.

It is necessary to refuse therapy with Valsacor:

• with renal artery stenosis, not on hemodialysis, with severe renal failure;
• with cirrhosis, severe hepatosis;
• acute dehydration;
• during pregnancy and lactation;
• in case of individual intolerance to the components.

Caution is required in various forms of cardiomyopathy, stenosis of the mitral valve or aorta.

Valsacor® h160 (Valsacor h160)

Valsartan

Clinically significant pharmacokinetic drug interactions with cimetidine, warfarin, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine and glibenclamide

not noted.

Since valsartan is not subject to significant metabolism, significant drug interactions associated with induction or inhibition of the cytochrome P450 system should not be expected.

Concomitant use of potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium-containing nutritional supplements, drugs that increase the level of potassium in the blood serum (ACE inhibitors, heparin, cyclosporine),

may lead to hyperkalemia and therefore require caution.

Concomitant use with other antihypertensive drugs, including diuretics,

leads to increased hypotensive effect.

When taking lithium drugs

and angiotensin II receptor antagonists, cases of a reversible increase in the content of lithium ions in the blood serum and an increase in its toxicity have been reported. Regular monitoring of lithium ion levels in the blood is recommended.

Hydrochlorothiazide

With thiazide diuretics, drugs such as ethanol, barbiturates

and
opioid analgesics
may potentiate the risk of orthostatic hypotension.

Hypoglycemic agents

(for oral administration and insulin): dose adjustment of hypoglycemic agents may be required.

Other antihypertensive drugs:

additive effect.

Anticholinergics (eg, atropine, biperiden)

increase the bioavailability of thiazide diuretics.

Cholestyramine and colestipol:

in the presence of anion exchange resins, the absorption of hydrochlorothiazide is reduced.

GCS, ACTH, laxatives, amphotericin B, carbenoxolone, benzathine benzylpenicillin, salicylic acid and salicylates:

a decrease in electrolyte levels, in particular hypokalemia, is possible; it is recommended to regularly monitor the content of potassium ions in the blood.

Class IA antiarrhythmics (quinidine, hydroquinidine, disopyramide), class III antiarrhythmics (amiodarone, dofetilide, ibutilide), sotalol, some antipsychotics (thioridazine, chlorpromazine, levomepromazine, trifluoroperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol , droperidol), other drugs (bepridil, cisapride, difemanil, erythromycin IV, halofantrine, ketanserin, mizolastine, pentamidine, sparfloxacin, terfenadine, vincamine IV):

the risk of developing ari against the background of possible hypokalemia and hypomagnesemia. It is recommended to monitor the content of potassium ions in the blood.

Cardiac glycosides:

the risk of developing arrhythmia due to hypokalemia and hypomagnesemia.

Beta blockers and diazoxide:

enhancing the hypoglycemic effect of these drugs.

Uricosuric agents (probenecid, sulfinpyrazone, allopurinol):

it is possible to increase the concentration of uric acid in the blood, as well as an increase in the frequency of hypersensitivity reactions to allopurinol; if necessary, adjust the dose of uricosuric drugs.

Pressor amines (eg, epinephrine, norepinephrine):

the effect of pressor amines may be reduced.

Amantadine:

the risk of side effects from amantadine increases.

Cytotoxic agents (eg, cyclophosphamide, methotrexate):

the excretion of cytotoxic drugs and potentiation of the myelosuppressive effect are reduced.

Non-depolarizing muscle relaxants (for example, tubocurarine):

enhancing the effect of muscle relaxants.

Cyclosporine:

the risk of hyperuricemia and gout-like complications increases.

Tetracyclines (except doxycycline):

risk of increased serum urea concentration.

Methyldopa:

Cases of hemolytic anemia have been described.

Lithium:

diuretics reduce the renal clearance of lithium and increase the risk of lithium toxicity; Monitoring lithium levels in the blood is recommended.

NSAIDs (including COX-2 inhibitors; e.g. salicylic acid, indoleacetic acid derivatives):

The diuretic, natriuretic and hypotensive effect of diuretics may decrease, and acute renal failure may develop.

Simultaneous use with calcium supplements, vitamin D

may lead to an increase in the content of calcium ions in the blood, which may distort the results of a study of parathyroid function.