Expiration date: 12/2025

The composition and form of issue:

Tablets, film-coated. 1 tablet contains:

valsartan 40, 80, 160 or 320 mg

other ingredients: microcrystalline crospovidone silicon dioxide colloidal anhydrous magnesium stearate hypromellose (hydroxypropylmethyl cellulose) macrogol 8000 titanium dioxide (E171) iron oxide red (E172) iron oxide yellow (E172) iron oxide black (E172), coated tablets, 40, 160 and 320 mg 

blister of 7 or 14 PCs. in cardboard pack 1, 2, 4, 7, 20 (7 PCs for dosage 320 mg) or 1, 2, 4, 7 (14 pieces for dosages of 40, 80 and 160 mg) blisters, or 120×8 (for the dosages of 80 mg) and 45×8 (for a dosage of 160 mg) blisters and in bottles of GGE at 56, 98 or 280 PCs (for dosage 320 mg).

Description pharmaceutical form:

The tablets, coated tablets, 40 mg: yellow oval with beveled edges on one side of the risk and embossed inscription "DO" on the other side — "NVR".

Tablets, film-coated, 80 mg: pale pink, round with beveled edges, on the one hand risk and embossed inscription "D/V" on the other hand — "NVR".

The tablets, coated tablets, 160 mg: grey-orange, oval, with one side of risk and embossed inscription "DX/DX" on the other hand, the "NVR".

The tablets, coated tablets, 320 mg: dark grey-violet, oval with bevelled edges, on the one hand risk and embossed inscription "DXL", on the other hand — "NVR".

Pharmacokinetics:

After taking the drug inside the absorption of valsartan occurs rapidly, but the degree of absorption varies widely. Average absolute bioavailability of the drug Diovan at 23%. T1/2 about 9 h In the range of doses studied kinetics valsartan is linear. With repeated drug use changes the kinetic parameters were noted. While taking the drug 1 time per day accumulation is negligible. The drug concentration in plasma in women and men were the same.

Valsartan largely (94-97%) is associated with serum proteins, mainly to albumin. VSS in the period of the equilibrium state is low (about 17 l). Compared with hepatic blood flow (about 30 l/h) plasma Cl is relatively slow valsartan (about 2 l/h). The amount of valsartan, excretiruthan with feces, 70% (of the value of oral dose). Urine output of about 30%, mainly in unchanged form. In appointing the drug Diovan with food decreases AUC by 48%, although from about 8 h after administration of 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, so the drug Diovan can be taken on an empty stomach, during meals.

Pharmacokinetics in specific groups of patients

Elderly patients. Some elderly valsartan AUC values were higher than those of the young adults, however, was not shown any clinical significance to this distinction.

Patients with impaired renal function. There was no correlation between renal function and AUC values of valsartan. In patients with impaired renal function dose adjustment of the drug is required. Currently, there are no data for patients on hemodialysis. Valsartan has a high degree of binding to blood plasma proteins, so its removal with hemodialysis is unlikely.

Patients with impaired liver function. About 70% of the value of the absorbed dose is excreted in the bile, mainly unchanged. Valsartan is not exposed to significant biotransformation, AUC valsartan not correlate with the degree of liver dysfunction. Therefore, in patients with hepatic insufficiency nobiliario of origin and in the absence of cholestasis is not required correction doses of the drug Diovan. It has been shown that patients with biliary cirrhosis or biliary obstruction AUC of valsartan is increased approximately in 2 times.

Description pharmacological action:

Drug Diovan 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 unlocked AT2 - receptors. Drug Diovan does not have any pronounced agonistic activity against AT1-receptors. The affinity of the drug Diovan for receptor subtype AT1 approximately 20,000 times higher than for the AT2 receptor subtype.

The probability of occurrence of cough with the use of valsartan is very low, due to the lack of effect on ACE, which is responsible for degradation of bradykinin. Comparison of drug Diovan with ACE inhibitor showed that the incidence of dry cough was significantly (p<0.05) lower in patients treated with Diovan drug than in patients receiving the ACE inhibitor (2.6 vs. 7.9 percent, respectively). In the group of patients who have previously, when treatment with ACE inhibitor developed a dry cough, in the treatment of drug Diovan this complication was noted in 19.5% of cases, in 19% of cases while in the group of patients treated with ACE inhibitor, cough was observed in 68.5% of cases (p<0.05). Valsartan does not enter into interaction and does not block other hormone receptors or ion channels of importance for the regulation of the functions of the cardiovascular system. In the treatment of drug Diovan patients with arterial hypertension there is a decrease in AD, is not accompanied by changes in heart rate.

After you assign inside dose of the drug, most patients start antihypertensive effect observed within 2 h, and the maximum decrease in blood pressure is achieved within 4-6 h After taking the drug antihypertensive effect persists over 24 h. With repeated prescriptions 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. The sudden discontinuation of the drug Diovan is not accompanied by a sharp increase in blood pressure or other undesirable clinical consequences.

The mechanism of action of the drug Diovan in chronic heart failure (CHF) based on its ability to eliminate the negative effects of chronic hyperactivation of the renin-angiotensin-aldosterone system (RAAS) 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, kidney, vessels) and stimulation of excess synthesis of hormones, acting synergistically with RA (catecholamines, aldosterone, vasopressin, endothelin, etc.). On the background of the use of valsartan in CHF decreases preload, decreases the pressure of jamming in pulmonary capillaries (ZLC) and DBP in the pulmonary artery, increased cardiac output. Along with hemodynamic effects, valsartan is mediated through the blockade of the synthesis of aldosterone reduces sodium retention and water in the body.

Established that the drug had no significant effect on the concentration of total cholesterol, uric acid, and also in the study on an empty stomach — the concentration of triglycerides and glucose in serum.

CHF

Hemodynamics and neurohormones. In patients with CHF (II–IV functional class NYHA classification) and DSLC &ge15 mm Hg.St. studied hemodynamics and concentration of neurohormones in the blood serum. Patients are constantly receiving ACE inhibitors, valsartan, appointed on a background of ACE inhibitor in single and repeated doses, has led to an improvement of hemodynamic parameters, including decrease JLC, DBP in the pulmonary artery and the garden. After 28 days of therapy were observed decrease in the concentrations of aldosterone and norarenalina in blood. In patients not treated with ACE inhibitors for at least 6 months, after 28 days of therapy valsartan was significantly decreased JLC, systemic vascular resistance, a garden and cardiac output.

The morbidity and mortality. Studied the effect of valsartan, compared with placebo, on morbidity and mortality in patients with CHF II (62%), III (36%) and IV (2%) functional class NYHA classification with the ejection fraction of the left ventricle (FULI) <40% and the internal diastolic diameter of the left ventricle (VDLI) >2.9 cm/m2 who are on the traditional therapy, which included ACE inhibitors (93%), diuretics (86%), digoxin (67%) and beta-blockers (36%). The average duration of follow-up time was almost 2 years, the average daily dose of the drug Diovan of 254 mg. Two primary performance criteria included all-cause mortality (time to death) and morbidity associated with heart failure (time to first event), which was evaluated by the following indicators: death, sudden death with resuscitation, hospitalization about heart failure in intravenous inotropic or vasodilator drugs for 4 hours or more without hospitalization. Mortality from all causes in the valsartan group and placebo was comparable. Compared with the placebo group, the incidence in the group of patients treated with valsartan, significantly decreased by 13.2%. The primary efficacy parameter was the reduction by 27.5% of the time to first hospitalization about heart failure. This effect was most pronounced in patients not treated with ACE inhibitors or beta-blockers.

Tolerance to physical load. In patients with chronic heart failure II–IV functional class NYHA classification with FWLI &le40% assessed the impact of valsartan, appointed in addition to the traditional treatment of chronic heart failure, exercise tolerance using the Modified Naughton Protocol. All therapeutic groups showed an increase time physical activity compared to the original. Compared with the placebo group, patients receiving valsartan was observed a larger average increase from initial level time physical activity, although this difference was not significant. The significant improvement of tolerance to physical load was observed in the subgroup of patients not receiving ACE inhibitors: average change time physical activity in groups of valsartan 2 times higher than those in the placebo group. The effect of valsartan on exercise tolerance, compared with enalapril, according to test 6-minute walk was studied in patients with heart failure II–IV functional class NYHA classification with FWLI &le45% received prior (at least within 3 months) therapy with ACE inhibitors. Patients were transferred to treatment with the ACE inhibitor or to receive valsartan or enalapril. Valsartan at doses of 80 to 160 mg 1 time per day was at least as effective as enalapril in doses of 5 to 10 mg 2 times a day.

NYHA class, symptoms, quality of life, ejection fraction. In patients receiving valsartan, there was a significant, compared with the placebo group, improvement in functional class CHF of NYHA classification, as well as the signs and symptoms of CHF, including such as shortness of breath, fatigue, peripheral edema, wheezing. Compared with the placebo group, patients who were taking valsartan, there was a significant increase in ejection fraction and a significant decrease VDLJ compared to baseline before treatment.

The use of the drug Diovan reduces the number of hospitalizations for CHF and to slow its progression, improve functional class NYHA, increase ejection fraction and decrease in the severity of signs and symptoms of heart failure and improve quality of life compared with placebo.

Use after acute myocardial infarction

In the VALIANT study was included 14703 patients with acute myocardial infarction complicated by left ventricular failure and/or systolic dysfunction of the left ventricle.

Randomization was carried out after 0.5–10 days after acute myocardial infarction in the groups in which, in addition to conventional therapy, treat, or with valsartan (4909 patients), or a combination of valsartan and captopril (4885 patients), or captopril (4909 patients).

Mortality for any cause and mortality from specific causes was similar in all 3 treatment groups. Only in the valsartan group died 979 (19.9 percent) in the combination therapy group — 941 (19.3 per cent) and in the group of captopril — 958 (19.5 per cent) patients.

The risk of death from cardiovascular causes and the risk for the composite indicator, which included, along with cases of cardiovascular death, serious nonfatal cardiovascular events (recurrent myocardial infarction, hospitalization in connection with heart failure, resuscitation after circulatory arrest and stroke) was similar for the valsartan group and the captopril group and for the group of combination therapy and captopril groups.

In the combination therapy group revealed the highest frequency of adverse events related to medication. When alone in the valsartan group were reported more often by hypotension and renal dysfunction in the group of captopril — cough, rash, and disorders of taste sensations.

Research has proven the effectiveness of valsartan, is equal to that of captopril in reducing total and cardiovascular mortality. The calculated effectiveness of valsartan in regards to the effect on the total mortality rate is 99.6% of that of captopril. Further analysis, conducted with the use of a placebo-assumptions showed that valsartan reduces the risk of fatalities by 25%. Valsartan is as effective as captopril in the treatment of patients with high risk of cardiovascular complications after myocardial infarction. The addition of valsartan to the treatment with captopril leads to an increased frequency of adverse effects without causing further improvements in survival of patients.

Indications:

• hypertension
  
• CHF (II–IV functional class classification NYHA) in patients receiving standard therapy, including diuretics, digitalis preparations, and ACE inhibitors or beta-blockers (not simultaneously)
  
• the improved survival of patients with acute myocardial infarction complicated by left ventricular failure and/or systolic dysfunction of the left ventricle, with the presence of stable hemodynamic parameters.
  

Contraindications:

• hypersensitivity to any component of the drug Diovan
  
• pregnancy
  
• the lactation period.
  

With caution:

• bilateral renal artery stenosis, stenosis of artery only kidneys
  
• diet with restriction of sodium
  
• state, accompanied by a decrease in BCC (W. diarrhea, vomiting)
  
• liver failure against the obstruction of the biliary tract
  
• renal failure (Cl creatinine less than 10 ml/min), including patients on hemodialysis (up to now, studies of the pharmacokinetics of the drug in patients, on hemodialysis, was not carried out).
  

The children, since controlled studies on the efficacy and safety of valsartan in children and adolescents (under 18 years) has not been conducted, it is not possible to formulate specific recommendations for use in this group of patients.

Application of pregnancy and breast-feeding:

Given the mechanism of action of antagonists of angiotensin II cannot exclude the risk to the fetus. The action of ACE inhibitors (drugs that affect the RAAS) on the fetus in case of their appointment in the II and III trimester of pregnancy, leading to 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 and impaired renal function in newborns whose mothers during pregnancy were receiving valsartan. The drug Diovan as well as any other drug that has a direct impact on the RAAS, should not be used during pregnancy and in women planning pregnancy. When assigning drugs acting on the RAAS, the physician should inform women of childbearing age about the potential risk of negative impact of these drugs on the fetus during pregnancy. If pregnancy is detected during treatment with the drug Diovan, the drug should be discontinued as soon as possible.

It is not known whether it penetrates valsartan (the active ingredient of the drug Diovan) in human breast milk, but in experimental models it was shown that valsartan is excreted in breast milk. Therefore, you should not use the drug Diovan in breast-feeding.

Side effects:

Not been shown of the frequency of any adverse events from the dose or duration of treatment, therefore, adverse events observed in the application of different doses of valsartan were combined. Incidence of adverse events was not associated with gender, age or race. See below for all the adverse events observed with a frequency of 1% or more in the group of patients receiving the drug Diovan, regardless of their causal relationship with the study drug and post-marketing data obtained in patients with arterial hypertension.

To assess the frequency of adverse events used the following criteria: very common (&GE. 1/10), often (&ge1/100, <1/10), sometimes (&ge1/1000, <1/100), rare (&ge1/10000, <1/1000), very rare (<1/10000).

Infections and infestations: often a viral infection sometimes infection of the upper respiratory tract, pharyngitis, sinusitis very rare — rhinitis.

With the hematopoietic system: often — neutropenia very rarely — thrombocytopenia.

The immune system: very rarely — hypersensitivity reactions, including serum sickness.

Metabolism: rarely — hyperkalemia.

From the nervous system: often — postural dizziness and sometimes fainting, insomnia, decreased libido dizziness very rare: headache.

On the part of the organ of hearing and labyrinth disorders: sometimes vertigo.

Of the cardiovascular system: often- orthostatic hypotension, sometimes — hypotension, heart failure very rare — vasculitis.

The respiratory system: sometimes — cough.

From the blood: sometimes — diarrhea, abdominal pain, rarely — nausea.

The skin and subcutaneous tissue: very rarely — angioneurotic edema, rash, itching.

From the side of musculoskeletal system: sometimes — pain in the back is very rarely — arthralgia, myalgia.

The kidneys: rarely — renal dysfunction, acute renal failure, renal failure.

Other: sometimes — fatigue, fatigue, swelling.

Changes in laboratory parameters: in rare cases, the use of the drug Diovan may be accompanied by decrease in hemoglobin concentration and hematocrit. In controlled clinical trials in 0.8% and 0.4% of patients receiving the drug Diovan, there was a marked decrease (>20%) in hematocrit and hemoglobin, respectively. For comparison — in patients treated with placebo, reduced as the hematocrit and hemoglobin observed in 0.1% of cases.

Neutropenia was detected in 1.9% of patients receiving the drug Diovan, and 1.6% of patients receiving ACE inhibitor.

A significant increase in the concentration of creatinine, potassium and total bilirubin in serum was observed, respectively, in 0.8, 4.4 and 6% of patients who took the drug Diovan, and at 1.6, 6.4 and 12.9 percent of patients treated with the ACE inhibitor. At HSN the increase in creatinine concentration by more than 50% were observed in 3.9% of patients who took the drug Diovan, compared with 0.9% in the placebo group. This increase in potassium level in the serum of more than 20% was noted in 10% of patients receiving the drug Diovan, and 5.1% of patients receiving placebo.

In the treatment of patients in the period after myocardial infarction increase in the concentration of serum creatinine in 2 times was noted in 4.2% of patients receiving valsartan and 4.8% of patients treated with valsartan + captopril, and 3.4% of patients receiving captopril.

There are reported cases of increase in liver transaminases in patients receiving the drug Diovan.

Increasing the concentration of urea nitrogen in serum by more than 50% were observed in 16.6% of patients treated with valsartan, and 6.3% of patients from the placebo group.

Note:

- 1 reported data on adverse events in patients receiving Diovan in the period after myocardial infarction

- 2 reported data on adverse events in CKD patients receiving the drug Diovan

- 3 reported data on adverse events with a frequency of sometimes patients receiving Diovan in the period after myocardial infarction

- 4 more frequently reported data on adverse events in CKD patients receiving the drug Diovan (often — dizziness, impaired renal function, hypotension, sometimes — headache, nausea).

All patients with CHF received traditional drug treatments for CHF, often — complex therapy, which included diuretics, digitalis preparations, beta-blockers or ACE inhibitors.

Long-term use valsartan in patients with CHF additional side effects were noted.

Drug interactions:

Clinically significant interactions with other drugs are still reported. We studied the interaction with the following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine and glibenclamide.

Because the drug Diovan is not exposed to significant metabolism, for it is unlikely clinically significant interactions with other drugs — inducers or inhibitors of cytochrome P450. Despite the fact that valsartan is largely associated with blood plasma proteins in vitro was not detected any interaction at this level with a number of molecules that have the same high binding to plasma proteins, such as diclofenac, furosemide and warfarin.

The simultaneous use of potassium-sparing diuretics (e.g. spironolactone, triamterene, amiloride), drugs or potassium salts, containing potassium, may lead to an increase in the concentration of potassium in serum in patients with heart failure — an increase in the concentration of serum creatinine. If such a combination treatment deemed necessary, caution must be exercised.

Method of application and dose:

Inside, not liquid.

Hypertension. The recommended dose is 80 mg 1 time a day every day, regardless of race, age and sex of the patient. The antihypertensive effect is observed in the first 2 weeks of treatment, maximum effect after 4 weeks. Those patients who fail to achieve adequate therapeutic response, the daily dose of drug Diovan can be increased to 320 mg or additionally appointed diuretics.

Chronic heart failure. The recommended initial dose of 40 mg 2 times a day, every day. The dose of the drug Diovan should be gradually increased to 80 mg 2 times a day, and with good endurance — up to 160 mg 2 times per day. This may require lower doses have also taken diuretics. The maximum daily — 320 mg in 2 admission. Assessment of patients with CHF should include an assessment of renal function.

Period after myocardial infarction. Treatment should begin within 12 hours after myocardial infarction. Initial dose — 20 mg (1/2 table. 40 mg) 2 times a day. The increase in dose is titration (40, 80 and 160 mg 2 times per day) in the next few weeks until the target dose is 160 mg 2 times per day. The maximum daily — 320 mg in 2 admission. Typically, the recommended dose to achieve 80 mg 2 times per day by the end of the second week of treatment. Achievement of the maximum target dose 160 mg 2 times a day is recommended by the end of the third month of drug therapy Diovan. The target dose depends on the tolerability valsartan during the period of titration. In the case of hypotension accompanied by clinical manifestations or renal dysfunction should consider lowering the dose. Assessment of patients in the period after myocardial infarction should include an assessment of renal function.

Note for all indications

It does not require correction of dosing regimen in patients with impaired renal function and patients with hepatic insufficiency debelyanovo origin without signs of cholestasis.

Overdose:

Symptoms: expressed lower AD, which can lead to collapse and/or shock.

Treatment: if the drug had been recently adopted, it should be cause vomiting in marked decrease in blood pressure the usual method of therapy is in/in the introduction 0.9% solution of sodium chloride. It is unlikely that valsartan can be derived from the body by hemodialysis.

Special instructions:

During the treatment of Diovan in patients with essential arterial hypertension requires regular monitoring of laboratory performance.

A deficiency of sodium and/or reduced BCC. Patients with severe deficiency of sodium and/or BCC, for example, receiving high doses of diuretics, in rare cases, early treatment can occur Diovan hypotension accompanied by clinical manifestations. Before treatment Diovan should be performed correction of content in the body of sodium and/or BCC, including by reducing the dose of diuretic effectively delivered.

In case of hypotension the patient should be laid, legs to lift. If you need to hold the on/in infusion 0.9% sodium chloride solution. After the AD stabilability, treatment can be continued.

Renal artery stenosis. The use of the drug Diovan short course in 12 patients with renovascular hypertension, which developed secondary to unilateral renal artery stenosis, has not led to any significant changes in renal hemodynamics, concentration of serum creatinine or urea nitrogen of the blood. However, given that other drugs, affecting the RAAS, can cause an increase in concentrations of urea and creatinine in the serum of patients with bilateral or unilateral renal artery stenosis, as a precautionary measure it is recommended to monitor these indicators.

Violations of kidney function. Patients with impaired renal function is not required correction doses of the drug. However, when expressed violations (when Cl creatinine less than 10 ml/min) caution should be used.

The liver dysfunction. In patients with hepatic failure is not required correction doses of the drug, except in cases of cholestasis. Valsartan is primarily excreted unchanged in the bile and it has been shown that in patients with obstruction of the biliary tract Cl valsartan reduced. In the appointment of valsartan to these patients should be particularly careful.

CHF/period after myocardial infarction. Patients with chronic heart failure or after myocardial infarction starting treatment with Diovan, it is frequently observed a decrease in blood pressure, therefore it is recommended to monitor AD at the beginning of therapy. Subject to recommendations for dosing regime there is usually no need of discontinuation of the drug Diovan because of hypotension. As a consequence of inhibiting the RAAS in sensitive patients possible changes of kidney function. In patients with severe CHF 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. Therefore, it is necessary to assess renal function in patients with heart failure and patients after acute myocardial infarction.

Combination therapy. Patients with CHF should exercise caution with the combination of ACE inhibitor, beta-blocker and valsartan.

Hypertension medication Diovan may be administered both as monotherapy or together with other antihypertensive agents, especially with diuretics.

At HSN Diovan drug can be administered both as monotherapy and in conjunction with other drugs — diuretics, digitalis preparations, and ACE inhibitors or beta-blockers.

Perhaps the use of the drug Diovan in combination with other drugs prescribed after myocardial infarction, namely with thrombolytic drugs, acetylsalicylic acid, beta-blockers and statins.

Effects on ability to drive a car and operate machinery. Patients taking the drug Diovan should be used with caution when driving a car and management mechanisms.