Expiration date: 01/2025
Dosage form
Oval biconvex tablets, film-coated brown colour, scored on one side tablets and two side risks, engraved "V" on the other side of the tablet (on the side without the risks).
Composition
1 tablet film-coated contains:
Active substance: valsartan 40, 80, 160 or 320 mg;
Excipients: lactose monohydrate -168,88 mg, microcrystalline cellulose - 144,00 mg croscarmellose sodium - 43,20 mg, povidone K29-32 -28,80 mg, talc - 7,20 mg, magnesium stearate - of 5.04 mg, silicon dioxide colloidal - 2,88 mg; Film cover: Opadry II brown 85G20236 - 28,8 mg (polyvinyl alcohol - 12,67 mg, talc - 5.76 mg, titanium dioxide - 4,46 mg, macrogol - 3350 - 3,56 mg lecithin -1,01 mg, dye sunset yellow aluminum lacquer - 0,95 mg, the colorant iron oxide black - 0,39 mg).
Pharmacological action
Valsartan - active specific antagonist of angiotensin II receptor intended for ingestion. Selectively blocks the AT1 receptor subtype which is responsible for the effects of angiotensin II. The consequence of the blockade AT1-receptors is increased plasma concentration of angiotensin II, which can stimulate tabletirovannye of ATG-receptors. Vallarta does not have any pronounced agonistic activity against AT1-receptors. The affinity of valsartan for receptor subtype AT1 about 20 000 times higher than for the AT2 receptor subtype.
Valsartan does not interact and does not block other hormone receptors or ion channels important in the regulation of the functions of the cardiovascular system.
The probability of occurrence of cough with the use of valsartan is very low, due to the lack of influence on angiotensinase enzyme (AMF), which is responsible for degradation of bradykinin.
When comparing valsartan with an ACE inhibitor, the incidence of dry cough was significantly (p < 0.05) lower in patients treated with valsartan than in patients treated with ACE inhibitor (2,6% vs 7.9%, respectively). In the group of patients who have previously, when treatment with ACE inhibitor developed a dry cough, the treatment with valsartan is an adverse event (AE) observed in 19.5% of cases, and in the treatment of thiazide diuretic - in 19,0% of cases, while in the group of patients who received treatment with ACE inhibitor, the cough is observed in 68.5% of cases (p < 0.05).
Application in arterial hypertension in patients over the age of 18
The treatment with valsartan in patients with arterial hypertension there is a decrease in blood pressure (BP), is not accompanied by change in heart rate.
After oral administration of a single dose of the drug in most patients beginning antihypertensive effect occurs within 2 hours, and maximum reduction of blood pressure is achieved within 4-6 h, persisting for more than 24 hours. With repeated use of the drug, the maximum decrease in blood pressure, regardless of the dose, is usually achieved within 2-4 weeks and maintained at that level during long-term therapy. In the case of simultaneous use of the drug is achieved gidrohlorotiazidom reliable additional decrease in blood pressure.
Abrupt discontinuation of valsartan not associated with a significant increase in blood pressure (the phenomenon of return) or other AES. In patients with hypertension, diabetes type 2 diabetes and nephropathy receiving valsartan at a dose of 160-320 mg, there is a significant decrease of proteinuria (36-44%).
Use after acute myocardial infarction in patients older than 18 years in the use of valsartan for 2 years in patients who started taking it in the period from 12 hours to 10 days after acute myocardial infarction (complicated by left ventricular failure and/or systolic left ventricular dysfunction), reduced total mortality, cardiovascular mortality, and increased time to first hospitalization for exacerbation of chronic heart failure (CHF), recurrent myocardial infarction, sudden cardiac arrest and stroke (with no fatalities). The safety profile of valsartan in patients with acute myocardial infarction are similar to those in other States.
CHF in patients older than 18 years
The mechanism of action of valsartan in CHF based PA is its ability to eliminate the negative effects of chronic hyperactivation of the renin-angiotensin-aldosterone system (GLAS) and its main effector of angiotensin II, namely, vasoconstriction; fluid retention in the body; the proliferation of cells, leading to remodeling of target organs (heart, nighttime, blood vessels); excessive stimulation of the synthesis of hormones, acting synergistically with RA (catecholamines, aldosterone, vasopressin, endothelia). The PA background of the use of valsartan in CHF decreases preload, decreases the pressure of jamming in pulmonary capillaries and diastolic pressure in the pulmonary artery, increased cardiac output. Along with hemodynamic effects of valsartan, due to the indirect blockade of the synthesis of aldosterone, decreases sodium retention and water in the body.
In General, the use of valsartan reduces the number of hospitalizations for CHF, slow progression of CHF and improve functional class but CHF classification of NYHA, increase ejection fraction of the left ventricle and reduces the severity of the signs and symptoms of heart failure and improve quality of life compared with placebo.
Use in patients older than 18 years with arterial hypertension and impaired glucose tolerance
When using valsartan and lifestyle change was a statistically significant reduction in the risk of developing diabetes in these patients.
Valsartan had no effect on the frequency of fatal outcomes resulting from cardiovascular events, myocardial infarction and ischemic attacks without fatalities, but on admission to hospital with heart failure or unstable angina, arterial revascularization, patients with impaired glucose tolerance and hypertension, but different age, sex and race.
Use in children and adolescents 6 to 18 years with arterial hypertension in children and adolescents 6 to 18 years valsartan provides dose-dependent, gradual decrease in blood pressure. When using valsartan maximum decrease in blood pressure, regardless of the dose, usually achieved within 2 weeks and maintained at that level during long-term therapy.
Pharmacokinetics
Suction
After taking valsartan inside its maximum concentration (Ssah) in the blood plasma is achieved within 2-4 hours. The average value of the absolute bioavailability of 23%. When taking valsartan with food, the area under the curve "concentration-time" (AUC) is reduced by the PA 48% although, from about 8 hours after taking the drug, the concentration of valsartan in plasma as in case of taking it on an empty stomach and when taken with food, the same. Reduction in AUC, however, is not accompanied by a clinically significant reduction in therapeutic effect, therefore, valsartan can be taken regardless of mealtime.
Distribution
The volume of distribution (UD valsartan during the period of the equilibrium state after intravenous (IV) injection was about 17 l, indicating the absence of Express distribution of valsartan in the tissues. Valsartan is largely associated with serum proteins (94-97%), mainly to albumin. Metabolism
Valsartan is not exposed to significant biotransformation (only about 20% of an oral dose is excreted as metabolites). The hydroxyl metabolite determined in plasma at low concentrations (less than 10% from the AUC valsartan). This metabolite is pharmacologically inactive.
Excretion
The pharmacokinetic curve is downward valsartan polyexponentially character (half-life initial phase (H|/2") less than I hour and the final phase of (Ti/2p) of about 9 hours). Valsartan is excreted mainly unchanged through the intestines (about 83%) and renal (around 13%). After the on/in the plasma clearance of valsartan is about 2 l/h and its renal clearance is of 0.62 l/h (about 30% of total clearance). The elimination half-life (T|/2) valsartan is 6 hours.
In the range of doses studied kinetics valsartan is linear. If you re-use valsartan changes in pharmacokinetic parameters were noted. When taking valsartan 1 time per day accumulation is negligible. The concentration of valsartan in plasma in women and men were the same. Pharmacokinetics in specific groups of patients Patients with CHF
In this category of patients, the time to reach S,sh and T|/2 are similar to those in healthy volunteers. Increase in AUC and C|SH is directly proportional to the increasing doses of the drug (40 mg and 160 mg 2 times per day). Factor accumulation is on average 1.7. At intake clearance of valsartan was approximately 4.5 l/h. the Age of patients with CHF had no effect on clearance of valsartan.
Elderly patients (over 65 years)
Some elderly patients, the systemic bioavailability of valsartan is higher than in patients of young age, however, it was identified that this has any clinical significance.
Patients with impaired renal function
There was no correlation between renal function and systemic biodostupnostthew valsartan. In patients with impaired renal function (creatinine clearance (CC) more than 10 ml/min) correction dose is not required. However valsartan has a high degree of binding to blood plasma proteins, so its removal with hemodialysis is unlikely.
Patients with abnormal liver function
About 70% of the absorbed valsartan dose is excreted through the intestine (with helcio), mostly unaltered. Valsartan NS undergoes significant biotransformation. In patients with light and moderate liver dysfunction there is an increase in bioavailability (AUC) of valsartan 2 times compared to healthy volunteers. However, there is no correlation in the values of AUC of valsartan with the degree of liver dysfunction. The use of the drug in patients with severely impaired hepatic function have not been studied.
Patients from 6 to 18 years
Pharmacokinetic properties of valsartan in children and adolescents from 6 to 18 lay not differ from the pharmacokinetic properties of valsartan in patients older than 18 years.
Side effects
In controlled clinical trials valsartan in adult patients with hypertension the incidence of adverse effects was comparable to placebo.
No data on the dependence of the frequency of any AES of the dose or duration of treatment, as well as gender, age or race. The safety profile of the drug, Valz patients with hypertension aged 6 to 18 years compared is different from the safety profile valsartan in adult patients.
Below OIA. observed during clinical studies, as well as when using the drug in clinical practice.
The frequency of side effektov: very often (>10%); often (>1% and <10%); infrequently (>0.1% and <1%); rare (>(),() 1% and <0,1%); very rare (<0,01 %), including individual messages; frequency unknown (frequency of development but available data cannot be set).
Within each group, the allocated frequency, IT is distributed in descending order of importance.
Patients with arterial hypertension
From the hematopoietic system and lymphatic system: frequency unknown-a decrease in hemoglobin, hematocrit, neutropenia, thrombocytopenia.
The immune system: frequency unknown - hypersensitivity reactions, including serum sickness.
From the metabolism and nutrition: the frequency is unknown - increase in the content of potassium in the blood hyponatremia.
On the part of the organ of hearing and labyrinth disorders: infrequent - vertigo.
From vessels: frequency unknown - vasculitis.
The respiratory system of the chest and mediastinum: rarely -cough.
The gastro-intestinal tract: rarely - pain in the abdomen.
The liver n of the biliary tract: the frequency is unknown - impaired liver function, including increasing the concentration of bilirubin in plasma.
The skin n subcutaneous tissue: very rarely - angioneurotic edema, skin rash, itching; frequency is unknown - bullous dermatitis.
From the musculoskeletal and connective tissue: frequency unknown - myalgia.
The kidneys and urinary tract: frequency is unknown - impaired renal function, increased creatinine concentration in blood serum.
Common disorders n disorders at the injection site:often - fatigue.
Also in clinical trials, valsartan in patients with arterial hypertension was observed following AES, the causal relationship of which his admission is not installed: arthralgia, asthenia, back pain, diarrhea, dizziness, insomnia, decreased libido, nausea, peripheral edema, pharyngitis, rhinitis, sinusitis, upper respiratory tract infection, viral infection.
Patients receiving valsartan after acute myocardial infarction and/or CHF
From the hematopoietic system, lymphatic system n: frequency unknown thrombocytopenia.
The immune system: frequency unknown - hypersensitivity reactions, including serum sickness.
From the metabolic and nutritional: rarely - hyperkalemia; frequency is unknown-increase in the content of potassium in the blood hyponatremia.
From the nervous system: often - dizziness, postural dizziness; rarely syncope, a headache.
On the part of the organ of hearing and labyrinth disorders: infrequent - vertigo.
Heart: rarely - increased symptoms of CHF.
From vessels: often - expressed lower AD, ortostatical gipotenzia; frequency is unknown - vasculitis.
The respiratory system of the chest and mediastinum: rarely -cough.
The gastro-intestinal tract: rarely - nausea, vomiting.
The liver and biliary tract disorders: frequency unknown - the liver.
The skin and subcutaneous tissue: rare - angioneurotic edema; frequency is unknown - skin rash, pruritus, bullous dermatitis.
From the musculoskeletal and connective tissue: rare - rhabdomyolysis; frequency is unknown - myalgia.
The kidneys and urinary tract: often - violation of the kidney; rarely, acute renal failure, increased creatinine concentration in blood serum; frequency is unknown - increase in the content of urea nitrogen in blood plasma. General disorders injection site: often - asthenia, fatigue.
Also in clinical trials, valsartan in patients after acute myocardial infarction and/or at khsp was observed following AES, the causal relationship of which his admission is not installed: arthralgia, abdominal pain, back pain, asthenia, insomnia, libido decrease, neutropenia, peripheral edema, pharyngitis, rhinitis, sinusitis, upper respiratory tract infection, viral infection.
Special conditions
In patients with severe deficiency of sodium in the body and/or reduced BCC, for example, as a result of receiving high doses of diuretics, in rare cases at the beginning of therapy with valsartan to develop severe hypotension. Before starting drug therapy, Valz is recommended to restore the contents of electrolytes and fluid in the body, in particular by reducing the doses of diuretics.
The drug of Valz can be used in conjunction with other drugs intended for the treatment of myocardial infarction, including thrombolytics, aspirin, beta-blockers, statins and diuretics. Joint reception of ACE inhibitors is not recommended.
When renovascular hypertension requires regular monitoring of urea and creatinine in the blood.
When used together with drugs containing potassium, its salts and preparations belonging to the group of potassium-sparing diuretics, conduct regular monitoring of potassium level in the blood plasma.
Patients with chronic heart failure, new treatment for Waltham, there may be some reduction in blood pressure, therefore it is recommended to monitor AD at the beginning of therapy.
As a consequence of inhibiting the renin-angiotensin-aldosterone system activity in some patients, changes of kidney function. In patients with severe CHF whose renal function depends on the activity of the renin-angiotensin-aldosterone system, treatment with ACE inhibitors and angiotensin receptor antagonists may be accompanied by oliguria and/or increasing azotemii and (rare) acute renal failure and/or death.
Does not recommend the combined use of the drug, Valz in patients suffering from CHF with ACE inhibitors and beta-blockers in view of the possible increased risk of side effects.
In patients with bilateral or unilateral renal artery stenosis requires regular monitoring of the content of creatinine and urea nitrogen in serum.
Effects on ability to drive and perform work requiring increased attention
During the period of treatment must be careful when driving and occupation of other potentially hazardous activities, require high concentration and speed motor and mental reactions.
For more information, see the user manual
Testimony
Adults
Hypertension.
Chronic heart failure (I1-IV functional class classification NYHA) in patients receiving standard therapy one or more drugs of the following pharmacological groups: diuretics, cardiac glycosides and ACE inhibitors or beta-blockers. The application of each of these drugs is not mandatory.
To improve the survival of patients after acute myocardial infarction complicated by left ventricular failure and/or systolic dysfunction of the left ventricle, with the presence of stable hemodynamic parameters.
Children and adolescents
Hypertension in children and adolescents 6 to 18 years.
Contraindications
- Hypersensitivity to any component of the drug;
- Severe violations of the liver (more 9 points on a scale child-Pyo), biliary cirrhosis and holstad;
- Pregnancy and lactation;
- The age of 6 - but the indication hypertension, to 18 years for other reasons (efficacy and safety not established);
- Simultaneous reception with aliskiren in patients with diabetes mellitus type 2 or impaired renal function (glomerular filtration rate < 60 ml/min/1.73 m2);
- Lactose intolerance, lactase deficiency, glucose-galactose malabsorption (the drug contains lactose monohydrate).
Bilateral renal artery stenosis; stenosis of the artery only kidneys; the primary giperaldosteronizm, diet with limited consumption of table salt; for conditions, accompanied by decreasing of volume of circulating blood (BCC) (including, diarrhea, and vomiting); severe renal failure (KK less 10 ml/min) since there are no clinical data; patients aged 6 to 18 years of age and KK less 30 ml/min, including hemodialysis; light and moderate liver dysfunction debelyanovo origin without signs of cholestasis, CHF 11-1V functional class (NYHA), mitral or aortic stenosis, hypertrophic obstructive cardiomyopathy, patients after renal transplantation; concomitant use of drugs that block the RAAS (ACE inhibitors, aliskiren).
Use during pregnancy and breastfeeding
Like any other medication affecting the RAAS, of Valz should not be used in women planning a pregnancy. In the appointment of any drug acting on the RAAS, the physician should inform women of childbearing age about the potential dangers of use of these drugs during pregnancy. The use of the drug, Valz during pregnancy is contraindicated because, given the mechanism of action of antagonists of angiotensin II receptors cannot be ruled out risk to the fetus. The action of ACE inhibitors (drugs that also affect the RAAS) on the fetus in case of their application in II and III trimestrah pregnancy can cause damage and death.
On retrospective data with the use of ACE inhibitors in the first trimester of pregnancy increases the risk of having children with birth defects. There are reports of spontaneous abortion, oligohydramnios (malovody) and renal dysfunction in newborns of mothers who during pregnancy inadvertently received valsartan.
If pregnancy is diagnosed during treatment with the drug, Valz, it should be abolished as quickly as possible.
Unknown, selects whether valsartan into breast milk in humans, therefore, contraindicated the apply of Valz in the period of breastfeeding.
Drug interactions
Dual blockade of the RA as antagonists of angiotensin receptors, ACE inhibitors or aliskiren:
Is contraindicated simultaneous reception of antagonists of angiotensin receptors (including valsartan), or ACE inhibitors with aliskiren in patients with diabetes mellitus type 2 or impaired renal function (glomerular filtration rate < 60 ml/min/1.73 m2).
The co-administration not recommended Drugs lithium
With simultaneous use of inhibitors AI1F the drug lithium marked reversible increase in lithium levels in the serum and result in intensification of e that its toxic action. Due to the lack of experience with lasartan with lithium, their concomitant use is not recommended. If necessary, the joint use of valsartan and lithium preparations necessary to ensure the control of the content of lithium in the blood serum.
Drugs that can increase potassium levels in the blood plasma
If necessary, the simultaneous application of biologically active additives, potassium-containing salt substitutes or other drugs that can raise potassium levels in the blood, there should be regular monitoring of the content of potassium in the blood plasma.
Combinations requiring caution in the use of Nonsteroidal anti-inflammatory drugs (IPVP)
While the use of valsartan NSAIDs (including selective cyclooxygenase-2 inhibitors) may decrease its antihypertensive action. When using angiotensin II receptor antagonists concurrently with NSAIDs may deterioration in renal function and increase in the content of potassium in the blood plasma. If necessary, the joint use of valsartan and NSAIDs before treatment it is necessary to assess renal function and correction of violations of water-electrolyte balance.
