Diovan, pills 160mg, 28pcs

Composition

Active ingredient:

valsartan 160 mg;

Auxiliary substances:  

MCC;

crospovidone; colloidal anhydrous silicon dioxide;

magnesium stearate;

hypromellose (hydroxypropylmethylcellulose);

macrogol 8000;

titanium dioxide (E 171);

iron oxide red (E 172);

iron oxide yellow (E 172)

Pharmacological action

Diovan® is an active, specific angiotensin II receptor antagonist intended for oral use. Selectively blocks AT1 subtype receptorsthat are responsible for the effects of angiotensin II. The consequence of AT1-receptor blockadeis an increase in the plasma concentration of angiotensin II, which can stimulate unblocked AT2_-receptors. The drug Diovan® does not have any pronounced agonistic activity against AT1receptors. The affinity of Diovan® for the AT_{1 subtype receptors} is approximately 20,000 times higher than for the AT_{2 subtype receptors}.

The probability of coughing when using valsartan is very low, which is due to the lack of influence 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 significantly higher (p) than in patients treated with an ACE inhibitor (2.6% vs. 7.9%, respectively). In the group of patients who had previously developed a dry cough during treatment with an ACE inhibitor, this complication was noted in 19.5% of cases when treated with Diovan®, in 19% of cases, while in the group of patients treated with an ACE inhibitor, cough was observed in 68.5% of cases (p®patients with arterial hypertension showed a decrease in Blood pressure that is not accompanied by a change in HR.

After oral use of a single dose of the drug in most patients, the onset of antihypertensive action is noted within 2 hours, and the maximum decrease in blood pressure is observed. Blood pressure is reached within 4-6 hours. After taking the drug, the antihypertensive effect persists for more than 24 hours. With repeated prescriptions of the drug, the maximum reduction in Blood pressure, regardless of the dose taken, is usually reached within 2-4 weeks and maintained at the achieved level during long-term therapy. Sudden discontinuation of Diovan® is not accompanied by a sharp increase in blood pressure. Blood pressure or other undesirable clinical consequences.

The mechanism of action of Diovan® in chronic heart failure (CHF) is based on its ability to eliminate the negative consequences of chronic hyperactivation of the renin-angiotensin-aldosterone system (RAAS) and its main effector, angiotensin II, namely, vasoconstriction, fluid retention in the body, cell proliferation leading to remodeling of target organs (heart, kidneys, blood vessels), stimulation of excessive synthesis of hormones acting synergistically with RAAS (catecholamines, aldosterone, vasopressin, endothelin, etc. ). Against the background of the use of valsartan in CHF, preload decreases, the pressure of jamming in the pulmonary capillaries (DLK) and dBP in the pulmonary artery decreases, and cardiac output increases. Along with the hemodynamic effects, valsartan reduces sodium and water retention in the body by indirectly blocking aldosterone synthesis.

It was found that the drug did not significantly affect the concentration of total cholesterol, uric acid, and also in the fasting study — on the concentration of triglycerides and glucose in the blood serum.

CHF

Hemodynamics and neurohormones. Hemodynamics and serum neurohormone concentrations were studied in patients with CHF (NYHA functional class II–IV) and DLC ≥15 mm Hg. In patients who are constantly receiving ACE inhibitors, valsartan, administered in single and repeated doses against the background of an ACE inhibitor, led to an improvement in hemodynamic parameters, including a decrease in DLC, dBP in the pulmonary artery and sBP. After 28 days of therapy, there was a decrease in the concentrations of aldosterone and norepinephrine in the blood. In patients who did not receive ACE inhibitors for at least 6 months, after 28 days of therapy, valsartan significantly reduced DLC, systemic vascular resistance, sBP, and cardiac output.

Morbidity and mortality. We studied the effect of valsartan on morbidity and mortality compared to placebo in patients with NYHA functional class II (62%), III (36%), and IV (2%) CHF with a left ventricular ejection fraction (LVEF) of 2.9 cm/m2 who were on conventional therapy, which included ACE inhibitors (93%), diuretics (86%), digoxin (67%), and beta-blockers (36%). The average follow — up period was almost 2 years, and the average daily dose of Diovan® was 254 mg. The two primary efficacy criteria included all-cause mortality (time to death) and heart failure-related morbidity (time to first event), which were evaluated by the following indicators: death, sudden death with intensive care, hospitalization for heart failure, intravenous use of inotropic or vasodilator drugs for 4 hours or more without hospitalization. The all-cause mortality rate in the valsartan and placebo groups was comparable. Compared with the placebo group, the incidence in the valsartan-treated group significantly decreased by 13.2%. The main parameter of effectiveness was a 27.5% reduction in the time to first hospitalization for heart failure. This effect was most pronounced in patients who did not receive ACE inhibitors or beta-blockers.

Tolerance to physical activity. In patients with NYHA functional class II–IV chronic heart failure with LVEF < 40%, the effect of valsartan administered in addition to traditional CHF treatment on exercise tolerance was evaluated using the Modified Naughton Protocol. In all treatment groups, there was an increase in the time of physical activity compared to the initial one. Compared with the placebo group, valsartan-treated patients showed a greater average 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 average change in exercise time 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 previous (at least 3 months) therapy with ACE inhibitors. Patients were transferred from ACE inhibitor treatment to either valsartan or enalapril. Valsartan at doses of 80 to 160 mg once daily was at least as effective as enalapril at doses of 5 to 10 mg twice daily.

NYHA class, symptoms, quality of life, ejection fraction. Patients treated with valsartan showed a significant improvement in the NYHA functional class of CHF, as well as signs and symptoms of CHF, including shortness of breath, increased fatigue, peripheral edema, and wheezing, compared to the placebo group. Compared with the placebo group, patients taking valsartan showed a significant increase in ejection fraction and a significant decrease in LVEF compared to baseline values before treatment.

The use of Diovan® leads to a decrease in the number of hospitalizations for CHF, slowing its progression, improving the NYHA functional class, increasing the ejection fraction, as well as reducing the severity of signs and symptoms of heart failure and improving the quality of life compared to placebo.

Use after acute myocardial infarction

The VALIANT study included 14,703 patients with acute myocardial infarction complicated by left ventricular failure and / or left ventricular systolic dysfunction.

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

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

The risk ratio for death from cardiovascular causes and the risk ratio for the composite indicator, which included, along with cases of cardiovascular death, serious non-fatal cardiovascular events (repeated myocardial infarction, hospitalization for 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, hypotension and impaired renal function were more common in the valsartan group, while cough, rash and taste disturbances were more common in the captopril group.

The study proved that valsartan is as effective as 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 conducted using the placebo-assumption method showed that valsartan reduces the risk of death by 25%. Valsartan is as effective as captopril in the treatment of patients at high risk of developing cardiovascular complications after a myocardial infarction. The addition of valsartan to captopril therapy leads to an increased incidence of adverse events, without causing an additional improvement in patient survival.

Pharmacokinetics

After oral use, valsartan is rapidly absorbed, but the degree of absorption varies widely. The average absolute bioavailability of Diovan® is 23%. T_1/2 is about 9 hours. In the range of 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 1 time a day, accumulation is insignificant. The concentrations of the drug in the blood plasma of women and men were the same.

Valsartan is largely (94-97%) bound to serum proteins, mainly albumin. V_SS is low during the equilibrium state (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 faeces is 70% (of the oral dose). About 30% is excreted in the urine, mostly unchanged. When Diovan® is administered with food, AUC is reduced by 48%, although starting from approximately 8 hours after taking the drug, plasma concentrations of valsartan are the same both when taken on an empty stomach and when taken with food. A decrease in AUC, however, is not accompanied by a clinically significant decrease in the therapeutic effect, so Diovan® can be taken both on an empty stomach and with meals.

Pharmacokinetics in selected groups of patients

Elderly patients. In some elderly individuals, valsartan AUC values were higher than those in young adults, but no clinical significance of this difference was shown.

Patients with impaired renal function. No correlation was found between renal function and valsartan AUC values. In patients with impaired renal function, no dose adjustment is required. Currently, there are no data available for patients undergoing hemodialysis. Valsartan has a high degree of binding to plasma proteins, so its elimination during hemodialysis is unlikely.

Patients with impaired liver function. About 70% of the absorbed dose of the drug is excreted in the bile, mainly in unchanged form. Valsartan does not undergo significant biotransformation, the AUC of valsartan does not correlate with the degree of impaired liver function. Therefore, in patients with non-biliary hepatic insufficiency and in the absence of cholestasis, no dose adjustment of Diovan®is required. Valsartan AUC has been shown to increase approximately 2-fold in patients with biliary cirrhosis or biliary tract obstruction.

Indications

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

Contraindications

• hypersensitivity to any of the components of the drug Diovan®;
• pregnancy;
• breast-feeding period.

With caution:

• bilateral renal artery stenosis, stenosis of the artery to a solitary kidney;
• a diet with restriction of sodium;
• state, accompanied by a decrease in BCC (including diarrhea, vomiting);
• hepatic insufficiency on the background of biliary tract obstruction;
• renal failure (Cl creatinine less than 10 ml/min), including patients undergoing hemodialysis (up to now, studies of the pharmacokinetics of the drug in patients on hemodialysis, have not been conducted).

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

Side effects

Infections and infestations: often-viral infections; sometimes-upper respiratory tract infections, 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.

Nervous system disorders: often-postural vertigo; sometimes-fainting, insomnia, decreased libido; rarely-dizziness; very rarely-headache.

Hearing disorders and labyrinth disorders: sometimes-vertigo.

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

Respiratory system disorders: sometimes-a cough.

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

Skin and subcutaneous tissue disorders: very rarely — angioedema; rash, pruritus.

Musculoskeletal disorders: sometimes-back pain; very rarely-arthralgia, myalgia.

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

Other services: sometimes-a feeling of fatigue, asthenia, edema.

How to take, course of use and dosage

Inside, without chewing.

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

Chronic heart failure. The recommended starting dose is 40 mg 2 times a day daily. The dose of Diovan® should be gradually increased to 80 mg 2 times a day, and if well tolerated – 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 dose is 320 mg in 2 divided doses. Assessment of patients with CHF should include assessment of renal function.

The period after a myocardial infarction. Treatment should be started within 12 hours after a previous myocardial infarction. The initial dose is 20 mg (1/2 table 40 mg) 2 times a day. Increasing the dose is carried out by titration (40,80 and 160 mg 2 times a day) for several subsequent weeks, until the target dose is reached — 160 mg 2 times a day. The maximum daily dose is 320 mg in 2 divided doses. As a rule, it is recommended to reach a dose of up to 80 mg 2 times a day by the end of the second week of treatment. Achieving the maximum target dose of 160 mg twice daily is recommended by the end of the third month of Diovan therapy. Achieving the target dose depends on the tolerability of valsartan during the titration period. In case of hypotension accompanied by clinical manifestations, or impaired renal function, the possibility of reducing the dose should be considered. Assessment of the condition of patients after a myocardial infarction should include an assessment of renal function.

Note for all readings

No dosage adjustment is required for patients with impaired renal function and patients with non-biliary hepatic insufficiency without cholestasis.

Overdose

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

Treatment: if the drug has been taken recently, you should induce vomiting; with a pronounced decrease in blood pressure, you should The usual method of therapy is intravenous use 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.

Lack of sodium in the body and / or a decrease in BCC. In patients with severe sodium and/or BCC deficiency, such as those receiving high-dose diuretics, hypotension may occur in rare cases at the beginning of treatment with Diovan®, accompanied by clinical manifestations. Before starting treatment with Diovan®, the body’s sodium and/or BCC content should be corrected, including by reducing the dose of the diuretic.

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

Renal artery stenosis. Application of the drug Diovan® a short course in 12 patients with renovascular hypertension, which developed a second time due 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 may 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.

Impaired renal function. Patients with impaired renal function do not need to adjust the dose of the drug. However, caution is recommended for severe disorders (when creatinine clearance is less than 10 ml / min).

Impaired liver function. In patients with hepatic insufficiency, no dose adjustment is required, except in cases of cholestasis. Valsartan is mainly excreted unchanged in the bile, and valsartan Cl has been shown to be reduced in patients with biliary tract obstruction. Special care should be taken when prescribing valsartan to these patients.

CHF/period after myocardial infarction. In patients with CHF or after a previous myocardial infarction, starting treatment with Diovan®, there is often a slight decrease Blood pressure, and therefore it is recommended to monitor blood pressure at the beginning of therapy. If the recommended dosage regimen is followed, it is usually not necessary to discontinue Diovan® due to hypotension. Due to RAAS inhibition, changes in renal function may occur in sensitive patients. In patients with severe CHF, treatment with ACE inhibitors and angiotensin receptor antagonists may be accompanied by oliguria and/or increased azotemia, and (rarely) acute renal failure and/or death. Therefore, it is necessary to evaluate renal function in patients with heart failure and patients who have suffered an acute myocardial infarction.

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

In patients with arterial hypertension, Diovan® can be prescribed both as monotherapy and in combination with other antihypertensive agents, in particular, with diuretics.

In patients with CHF, Diovan® can be prescribed either as monotherapy or in combination with other drugs — diuretics, digitalis preparations, as well as ACE inhibitors or beta-blockers.

It is possible to use Diovan® in combination with other medications prescribed after a previous 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 exercise caution when driving a car and operating mechanisms.

Composition

Tablet Form of production

Storage conditions

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

Shelf life

3 years

Active ingredient

Valsartan

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For children over 6 years of age, For adults as prescribed by a doctor, For children as prescribed by a doctor

Indications

Hypertension, Heart Failure, Myocardial Infarction