Diovan, 160 mg, 28 pcs.

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Product Description

Composition

Active substance :

 valsartan 160 mg;

Excipients: 

MCC;

crospovidone; anhydrous colloidal silicon dioxide;

magnesium stearate;

hypromellose (hydroxypropyl methylcellulose);

macrogol 8000;

titanium dioxide (E171);

iron oxide red (E172);

iron oxide yellow (E172)

pharmachologic effect

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

The likelihood of coughing with valsartan is very low, which is due to the lack of effect on ACE, which is responsible for the degradation of bradykinin. Comparison of Diovan ®  with an ACE inhibitor showed that the incidence of dry cough was significant (p ® than in patients who received an ACE inhibitor (2.6% versus 7.9%, respectively). In the group of patients who had previously received an ACE inhibitor He developed a dry cough, in the treatment of drug Diovan ®  this complication was observed in 19.5% of cases, in 19% of cases - while in the group of patients treated with ACE inhibitor, coughing was observed in 68.5% of cases (r® in patients with arterial hypertension, a decrease in blood pressure is noted, not accompanied by a change in heart rate.

After a single dose of the drug is administered orally, in most patients, the onset of the antihypertensive action is observed within 2 hours, and the maximum decrease in blood pressure is achieved within 4-6 hours. After taking the drug, the antihypertensive effect persists for more than 24 hours. from the dose taken, is usually achieved within 2-4 weeks and is maintained at the achieved level during long-term therapy. Sudden discontinuation of 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) is based on its ability to eliminate the negative effects of chronic hyperactivation of the renin-angiotensin-aldosterone system (RAAS) and its main effector, angiotensin II, namely vasoconstriction, fluid retention in the body, cell proliferation leading to organ remodeling -targets (heart, kidneys, blood vessels), stimulation of excessive synthesis of hormones that act synergistically with the RAAS (catecholamines, aldosterone, vasopressin, endothelin, etc.). Against the background of the use of valsartan in CHF, the preload decreases, the pressure of wedging in the pulmonary capillaries (PLC) and DAD in the pulmonary artery decreases, and cardiac output increases. Along with the hemodynamic effects, valsartan, due to the indirect blockade of aldosterone synthesis, reduces sodium and water retention in the body.

It was found that the drug had no significant effect on the concentration of total cholesterol, uric acid, as well as in the study on an empty stomach - on the concentration of triglycerides and glucose in the blood serum.

CHF

Hemodynamics and neurohormones. In patients with CHF (II – IV functional class according to NYHA classification) and DZLK ≥15 mm Hg. studied hemodynamics and concentration of neurohormones in blood serum. In patients constantly receiving ACE inhibitors, valsartan, prescribed against the background of an ACE inhibitor in single and repeated doses, led to an improvement in hemodynamic parameters, incl. to decrease DZLK, DBP in the pulmonary artery and SBP. After 28 days of therapy, a decrease in blood concentrations of aldosterone and norepinephrine was observed. In patients who did not receive ACE inhibitors for at least 6 months, after 28 days of therapy, valsartan significantly reduced the DZLK, systemic vascular resistance, systolic blood pressure and cardiac output.

Morbidity and mortality. The effect of valsartan, compared with placebo, on morbidity and mortality in patients with CHF II (62%), III (36%) and IV (2%) functional class according to the NYHA classification with a left ventricular ejection fraction (LVEF) was studied. cm / m 2 , which were on traditional therapy, which included ACE inhibitors (93%), diuretics (86%), digoxin (67%) and beta-blockers (36%). The average duration of the observation period was almost 2 years, the average daily dose of Diovan ® - 254 mg. The two primary efficacy measures included all-cause mortality (time to death) and heart failure-related morbidity (time to first event), which were assessed by the following indicators: death, sudden death with resuscitation, hospitalization for heart failure, IV injection inotropic or vasodilator drugs for 4 hours or more without hospitalization. All-cause mortality rates were comparable between the valsartan and placebo groups. Compared with the placebo group, the incidence in the group of patients receiving valsartan significantly decreased by 13.2%. The main efficacy parameter was a 27.5% reduction in time to first hospitalization for heart failure. This effect was most pronounced in patients who did not receive ACE inhibitors or beta-blockers.

Physical exercise tolerance. In patients with chronic heart failure II – IV functional class according to NYHA classification with LVEF ≤40%, the effect of valsartan, prescribed in addition to traditional treatment of CHF, on exercise tolerance was assessed using the Modified Naughton Protocol. In all treatment groups, there was an increase in exercise time compared to baseline. Compared with the placebo group, patients treated with valsartan had a larger mean increase from baseline in exercise time, although this difference was not significant. The most pronounced improvement in exercise tolerance was observed in the subgroup of patients who did not receive ACE inhibitors: the mean change in the time of exercise in the valsartan groups was 2 times higher than in the placebo group. The effect of valsartan on exercise tolerance, compared with enalapril, according to the 6-minute walk test was studied in patients with NYHA functional class II – IV heart failure with LVEF ≤45% who received prior (at least 3 months) therapy ACE inhibitors. Patients were transferred from treatment with an ACE inhibitor to either valsartan or enalapril. Valsartan at doses ranging from 80 to 160 mg once daily was at least as effective as enalapril at doses ranging from 5 to 10 mg twice daily. Patients were transferred from treatment with an ACE inhibitor to either valsartan or enalapril. Valsartan at doses ranging from 80 to 160 mg once daily was at least as effective as enalapril at doses ranging from 5 to 10 mg twice daily. Patients were transferred from treatment with an ACE inhibitor to either valsartan or enalapril. Valsartan in doses ranging from 80 to 160 mg once a day was at least as effective as enalapril in doses from 5 to 10 mg twice a day.

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

Use of Diovan drug ®  leads to a decrease in the number of hospitalizations for CHF, slowing its progression, improve the NYHA functional class, increased ejection fraction, as well as reduces the severity of signs and symptoms of heart failure and improvement of quality of life compared with placebo.

Application after acute myocardial infarction

The VALIANT study included 14703 patients with acute myocardial infarction complicated by left ventricular failure and / or left ventricular systolic dysfunction.

Randomization was carried out 0.5-10 days after acute myocardial infarction, in groups in which, in addition to conventional treatment, treatment was started with either valsartan (4909 patients), or a combination of valsartan and captopril (4885 patients), or captopril (4909 sick).

The rates of mortality from any cause and mortality from specific causes were similar in all 3 treatment groups. In total, 979 (19.9%) patients died in the valsartan group, 941 (19.3%) in the combination therapy group, and 958 (19.5%) patients in the captopril group.

Ratio of risk of death from cardiovascular causes and risk ratio for a composite indicator that included, along with cardiovascular deaths, serious non-fatal cardiovascular events (recurrent myocardial infarction, hospitalization due to heart failure, resuscitation after circulatory arrest, and stroke) were similar for the valsartan group and the captopril group, as well as for the combination therapy group and the captopril group.

The combination therapy group showed the highest frequency of drug-related adverse events. With monotherapy, in the valsartan group, hypotension and renal dysfunction were more often observed, in the captopril group - cough, rash and taste disturbances.

The study proved the effectiveness of valsartan, equal to that of captopril, in reducing overall and cardiovascular mortality. The calculated efficacy of valsartan in relation to the effect on the overall mortality rate is 99.6% of that of captopril. An additional analysis using the placebo-assumption method showed that valsartan reduced the risk of death by 25%. Valsartan is as effective as captopril in the treatment of patients with a high risk of cardiovascular complications after myocardial infarction. The addition of valsartan to captopril therapy leads to an increase in the incidence of adverse events, without causing an additional improvement in patient survival.

Pharmacokinetics

After taking the drug inside, the absorption of valsartan occurs quickly, but the degree of absorption varies widely. The average value of the absolute bioavailability of Diovan ®  is 23%. T 1/2  - about 9 hours. In the range of the studied doses, the kinetics of valsartan is linear. With repeated use of the drug, no changes in kinetic parameters were observed. When taking the drug once a day, the cumulation is insignificant. Plasma concentrations of the drug in women and men were the same.

Valsartan to a large extent (94–97%) binds to serum proteins, mainly albumin. V SS  during the equilibrium state is low (about 17 L). Compared to hepatic blood flow (about 30 l / h), plasma Cl of valsartan occurs relatively slowly (about 2 l / h). The amount of valsartan excreted in the feces is 70% (of the amount taken orally). About 30% is excreted in the urine, mainly unchanged. When prescribing Diovan ® with food, AUC decreases by 48%, although, starting from about 8 hours after taking the drug, the concentration of valsartan in plasma, both in the case of taking it on an empty stomach, and in the case of taking it with food, are the same. Reducing AUC, however, is not accompanied by a clinically significant decrease in the therapeutic effect, so the drug Diovan ®  can be taken on an empty stomach, and at mealtime.

Pharmacokinetics in certain groups of patients

Elderly patients. In some elderly people, the AUC values ​​of valsartan were higher than those in young people, however, no clinical significance of this difference was shown.

Patients with impaired renal function. There was no correlation between renal function and valsartan AUC values. In patients with impaired renal function, dose adjustment is not required. There are currently no data available for patients on hemodialysis. Valsartan has a high degree of binding to blood plasma proteins, therefore, its excretion during hemodialysis is unlikely.

Patients with impaired liver function. About 70% of the absorbed dose of the drug is excreted in the bile, mainly unchanged. Valsartan does not undergo significant biotransformation, valsartan AUC does not correlate with the degree of liver dysfunction. Therefore, in patients with hepatic failure of non-biliary origin and in the absence of cholestasis, dose adjustment of Diovan ® is not required . It has been shown that in patients with biliary cirrhosis or obstruction of the biliary tract, the AUC of valsartan increases approximately 2 times.

Indications

  • arterial hypertension;
  • CHF (II – IV functional class according to NYHA classification) in patients receiving standard therapy, incl. diuretics, digitalis drugs, as well as ACE inhibitors or beta-blockers (not simultaneously);
  • increasing the survival rate of patients with acute myocardial infarction complicated by left ventricular failure and / or left ventricular systolic dysfunction, in the presence of stable hemodynamic parameters.

Contraindications

  • hypersensitivity to any component of Diovan ® ;
  • pregnancy;
  • breastfeeding period.

Carefully:

  • bilateral stenosis of the renal arteries, stenosis of the artery of a single kidney;
  • adherence to a sodium-restricted diet;
  • conditions accompanied by a decrease in the BCC (including diarrhea, vomiting);
  • hepatic failure against the background of obstruction of the biliary tract;
  • renal failure (Cl creatinine less than 10 ml / min), incl. patients on hemodialysis (to date, studies of the pharmacokinetics of the drug in patients on hemodialysis have not been conducted).

Use in children - since no controlled studies on the efficacy and safety of valsartan in children and adolescents (under 18 years of age) have been conducted, it is not possible to formulate specific recommendations for use in this group of patients.

Side effects

Infections and invasions: often - viral infections; sometimes - infections of the upper respiratory tract, pharyngitis, sinusitis; very rarely - rhinitis.

From the hematopoietic system: often - neutropenia; very rarely - thrombocytopenia.

From the immune system: very rarely - hypersensitivity reactions, including serum sickness.

Metabolic disorders: sometimes - hyperkalemia.

From the nervous system: often - postural dizziness; sometimes - fainting, insomnia, decreased libido; rarely - dizziness; very rarely - headache.

From the side of the organ of hearing and labyrinth disorders: sometimes - vertigo.

From the side of the cardiovascular system: often - orthostatic hypotension; sometimes - hypotension, heart failure; very rarely - vasculitis.

From the respiratory system: sometimes - cough.

From the digestive tract: sometimes - diarrhea, abdominal pain; very rarely - nausea.

On the part of the skin and subcutaneous tissue: very rarely - angioedema; rash, itching.

From the musculoskeletal system: sometimes - back pain; very rarely - arthralgia, myalgia.

From the side of the kidneys: very rarely - impaired renal function, acute renal failure, renal failure.

Others: sometimes - feeling tired, asthenia, edema.

How to take, course of administration and dosage

Inside without chewing.

Arterial hypertension. The recommended dose is 80 mg once a day every day, regardless of the race, age and sex of the patient. The antihypertensive effect is observed in the first 2 weeks of treatment, the maximum effect is observed after 4 weeks. For those patients who fail to achieve an adequate therapeutic response, the daily dose of Diovan ®  can be increased to 320 mg or diuretics may be additionally prescribed.

Chronic heart failure. The recommended starting dose is 40 mg 2 times a day. The dose of Diovan ®  should be gradually increased to 80 mg 2 times a day, and with good tolerance - up to 160 mg 2 times a day. In this case, it may be necessary to reduce the doses of simultaneously taken diuretics. The maximum daily allowance is 320 mg in 2 divided doses. Assessment of the condition of patients with CHF should include an assessment of renal function.

The period after suffering myocardial infarction. Treatment should be started within 12 hours after myocardial infarction. The initial dose is 20 mg (1/2 table. 40 mg) 2 times a day. The dose is increased by titration (40, 80 and 160 mg 2 times a day) over the next several weeks, until the target dose is reached - 160 mg 2 times a day. The maximum daily allowance is 320 mg in 2 divided doses. As a rule, it is recommended to achieve a dose of up to 80 mg 2 times a day by the end of the second week of treatment. Achievement of the maximum target dose of 160 mg 2 times a day is recommended by the end of the third month of therapy with Diovan ®... Achievement of the target dose depends on the tolerability of valsartan during the titration period. In the case of hypotension, accompanied by clinical manifestations, or impaired renal function, a dose reduction should be considered. Assessment of the condition of patients in the period after myocardial infarction should include an assessment of renal function.

Note for all indications

No correction of the dosage regimen is required for patients with impaired renal function and patients with hepatic insufficiency of non-biliary genesis without cholestasis.

Overdose

Symptoms: A marked decrease in blood pressure, which can lead to collapse and / or shock.

Treatment: if the drug has been recently taken, induce vomiting; with a pronounced decrease in blood pressure The usual method of therapy is intravenous administration of 0.9% sodium chloride solution. It is unlikely that valsartan can be eliminated from the body by hemodialysis.

Special instructions

During treatment with Diovan ®  in patients with essential arterial hypertension, regular monitoring of laboratory parameters is not required.

Deficiency in the body of sodium and / or a decrease in BCC. In patients with a pronounced deficiency in the body of sodium and / or BCC, for example, receiving high doses of diuretics, in rare cases, at the beginning of treatment with Diovan ®  , hypotension may occur, accompanied by clinical manifestations. Before starting treatment with Diovan ®  , the sodium and / or BCC content in the body should be corrected, including by reducing the dose of the diuretic.

If hypotension develops, the patient should be laid down, legs raised. If necessary, conduct an intravenous infusion of 0.9% sodium chloride solution. After BP stabilizes, treatment can be continued.

Renal artery stenosis. The use of Diovan ® in a  short course in 12 patients with renovascular hypertension, secondary to unilateral renal artery stenosis, did not lead to any significant changes in renal hemodynamics, serum creatinine concentration or blood urea nitrogen. However, given that other drugs that affect the RAAS can cause an increase in serum urea and creatinine concentrations in patients with bilateral or unilateral renal artery stenosis, monitoring of these parameters is recommended as a precautionary measure.

Renal dysfunction. Patients with impaired renal function do not require dose adjustment of the drug. However, in severe disorders (when Cl creatinine is less than 10 ml / min), caution is recommended.

Liver dysfunction. In patients with hepatic insufficiency, no dose adjustment is required, except in cases of cholestasis. Valsartan is excreted mainly unchanged in the bile, and it has been shown that in patients with obstruction of the biliary tract Cl of valsartan is reduced. When prescribing valsartan, these patients should be especially careful.

CHF / period after myocardial infarction. In patients with CHF or after myocardial infarction who begin treatment with Diovan ® , a slight decrease in blood pressure is often noted, and therefore it is recommended to control blood pressure at the beginning of therapy. Subject to the recommendations on the dosage regimen, there is usually no need to discontinue Diovan ® due to hypotension. Due to inhibition of the RAAS in sensitive patients, changes in renal function are possible. In patients with severe CHF, treatment with ACE inhibitors and angiotensin receptor antagonists may be accompanied by oliguria and / or an increase in azotemia and (rarely) acute renal failure and / or death. Therefore, it is necessary to assess renal function in patients with heart failure and in patients with acute myocardial infarction.

Combined therapy. In patients with CHF, caution should be exercised when using a combination of an ACE inhibitor, a beta-blocker and valsartan.

In case of arterial hypertension, Diovan ®  can be prescribed both as monotherapy and in conjunction with other antihypertensive drugs, in particular, with diuretics.

In CHF, Diovan ®  can be prescribed both as monotherapy and in conjunction with other drugs - diuretics, digitalis drugs, as well as ACE inhibitors or beta-blockers.

It is possible to use the drug Diovan ®  in combination with other drugs prescribed after myocardial infarction, namely thrombolytics, acetylsalicylic acid, beta-blockers and statins.

Influence on the ability to drive a car and work with mechanisms. Patients taking Diovan ® should be careful when driving and operating machinery.

Release form

pills

Storage conditions

In a dry place, at a temperature not exceeding 30 ° C

Shelf life

3 years