Composition, form of production and packaging
The tablets covered with a cover of yellow color, oval, with bevelled edges, on one side of risk and squeezed out inscription "DO", on the other side - "NVR".
1 tab.
valsartan 40 mg
Auxiliary substances: microcrystalline cellulose, crospovidone, silicon dioxide, colloid anhydrous, magnesium stearate, hypromellose (hydroxypropylmethylcellulose), macrogol 8000, titanium dioxide (E171), iron oxide yellow (E172), iron oxide red (E172), iron oxide black (E172) .
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
14 pcs. - blisters (4) - packs of cardboard.
14 pcs. - blisters (7) - packs of cardboard.
The pills covered with a pale pink coating are round, with beveled edges, on one side of the risk and the squeezed out inscription "D / V", on the other hand - "NVR".
1 tab.
valsartan 80 mg
Excipients: microcrystalline cellulose, crospovidone, silicon dioxide, colloid anhydrous, magnesium stearate, hypromellose (hydroxypropylmethylcellulose), macrogol 8000, titanium dioxide (E171), iron oxide red (E172), iron oxide yellow (E172).
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
14 pcs. - blisters (4) - packs of cardboard.
14 pcs. - blisters (7) - packs of cardboard.
The tablets, covered with a coat of gray-orange color, are oval, on the one side of the risk and squeezed out the inscription "DX / DX", on the other hand - "NVR".
1 tab.
valsartan 160 mg
Auxiliary substances: microcrystalline cellulose, crospovidone, silicon dioxide, colloid anhydrous, magnesium stearate, hypromellose (hydroxypropylmethylcellulose), macrogol 8000, titanium dioxide (E171), iron oxide red (E172), iron oxide yellow (E172), iron oxide black (E172) .
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
14 pcs. - blisters (4) - packs of cardboard.
14 pcs. - blisters (7) - packs of cardboard.
The tablets covered with a cover of dark gray-violet color, oval, with bevelled edges, on one side of risk and squeezed out inscription "DXL", on the other side - "NVR".
1 tab.
valsartan 320 mg
Auxiliary substances: microcrystalline cellulose, crospovidone, silicon dioxide, colloid anhydrous, magnesium stearate, hypromellose (hydroxypropylmethylcellulose), macrogol 8000, titanium dioxide (E171), iron oxide yellow (E172), iron oxide red (E172), iron oxide black (E172) .
7 pcs. - blisters (1) - packs of cardboard.
7 pcs. - blisters (2) - packs of cardboard.
7 pcs. - blisters (4) - packs of cardboard.
7 pcs. - blisters (7) - packs of cardboard.
7 pcs. - blisters (20) - packs of cardboard.
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
14 pcs. - blisters (4) - packs of cardboard.
14 pcs. - blisters (7) - packs of cardboard.
14 pcs. - blisters (20) - packs of cardboard.
56 pcs. - bottles.
98 pcs. - bottles.
280 pcs. - bottles.
The tablets, covered with a coat of gray-orange color, are oval, on the one side of the risk and squeezed out the inscription "DX / DX", on the other hand - "NVR".
1 tab.
valsartan 160 mg
Auxiliary substances: microcrystalline cellulose, crospovidone, silicon dioxide, colloid anhydrous, magnesium stearate, hypromellose (hydroxypropylmethylcellulose), macrogol 8000, titanium dioxide (E171), iron oxide red (E172), iron oxide yellow (E172), iron oxide black (E172) .
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
14 pcs. - blisters (4) - packs of cardboard.
14 pcs. - blisters (7) - packs of cardboard.
The tablets covered with a cover of yellow color, oval, with bevelled edges, on one side of risk and squeezed out inscription "DO", on the other side - "NVR".
1 tab.
valsartan 40 mg
Auxiliary substances: microcrystalline cellulose, crospovidone, silicon dioxide, colloid anhydrous, magnesium stearate, hypromellose (hydroxypropylmethylcellulose), macrogol 8000, titanium dioxide (E171), iron oxide yellow (E172), iron oxide red (E172), iron oxide black (E172) .
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
14 pcs. - blisters (4) - packs of cardboard.
14 pcs. - blisters (7) - packs of cardboard.
The pills covered with a pale pink coating are round, with beveled edges, on one side of the risk and the squeezed out inscription "D / V", on the other hand - "NVR".
1 tab.
valsartan 80 mg
Excipients: microcrystalline cellulose, crospovidone, silicon dioxide, colloidal anhydrous, magnesium stearate, hypromellose (hydroxypropylmethylcellulose), macrogol 8000, titanium dioxide (E171), iron oxide red (E172), iron oxide yellow (E172).
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
14 pcs. - blisters (4) - packs of cardboard.
14 pcs. - blisters (7) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
PHARMACHOLOGIC EFFECT
Specific antagonist of angiotensin II receptors. Selectively blocks receptors of the subtype AT 1 , which are responsible for the known 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. Diovan does not have any expressed agonistic activity against AT 1 -receptors. The affinity of Diovan to the receptors of the AT1 subtype is approximately 20,000 times higher than to the receptors of the AT2 subtype.
The likelihood of coughing with valsartan is very low, which is due to the lack of influence on the ACE, which is responsible for the degradation of bradykinin. A comparison of Diovan with an ACE inhibitor showed that the incidence of dry cough was significantly (p <0.05) lower in patients receiving Diovan В® than in patients receiving an ACE inhibitor (2.6% versus 7.9%, respectively). In patients who previously developed a dry cough during treatment with an ACE inhibitor, 19.5% of cases were observed with Diovan treatment, and in the treatment with a thiazide diuretic in 19.0% of cases, while in the group of patients treated with an ACE inhibitor, cough was observed in 68.5% of cases (p <0.05). Valsartan does not interact and does not block the receptors of other hormones or ion channels, which are important for the regulation of the functions of the cardiovascular system.
When treating Diovan patients with hypertension, there is a decrease in blood pressure, not accompanied by a change in heart rate.
After administration 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 achieved within 4-6 hours. After taking the drug, the antihypertensive effect persists for more than 24 hours. For repeated prescriptions of the drug, the maximum decrease in blood pressure, of the accepted dose, is usually achieved within 2-4 weeks and maintained at the achieved level during prolonged therapy. In the case of a combination of the drug with hydrochlorothiazide, a significant additional reduction in blood pressure is achieved.
The sudden discontinuation of taking Diovan is not accompanied by a sharp increase in 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 RAAS and its main effector, angiotensin II, vasoconstriction; fluid retention in the body; cell proliferation leading to remodeling of target organs (heart, kidneys, vessels);stimulation of excessive synthesis of hormones acting synergistically with RAAS (catecholamines, aldosterone, vasopressin, endothelin). Against the background of the use of valsartan in CHF, prednagruzka decreases, the wedging pressure in the pulmonary capillaries (DZLK) decreases and the diastolic pressure in the pulmonary artery increases, the cardiac output increases. Along with hemodynamic effects, valsartan, due to the mediated blockade of aldosterone synthesis, reduces the retention of sodium and water 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 of fasting - the concentration of triglycerides and glucose in the blood serum.
Chronic heart failure (CHF)
Hemodynamics and neurohormones. In two short-term studies in patients with CHF (II-IV functional class according to the NYHA classification) and pulmonary capillary wedging pressure (DZLK), 15 mm Hg. studied hemodynamics and the level of neurohormones in the blood serum. In patients who are 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 a decrease in DZLK, diastolic pressure in the pulmonary artery and systolic BP (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 DZLK, systemic vascular resistance, SBP, and cardiac output.
Morbidity and mortality. The effect of valsartan, in comparison with placebo, on morbidity and mortality in patients with chronic heart failure II (62%), III (36%) and IV (2%) functional class according to NYHA classification with left ventricular ejection fraction (LVEF) < (93%), diuretics (86%), digoxin (67%), and beta-blockers (36%), and left ventricular internal diastolic diameter (LVLD)> 2.9 cm / m 2 . ). The average duration of the observation period was almost 2 years; the average daily dose of Diovan is 254 mg. Two primary efficacy criteria included mortality from all causes (time to death) and incidence of heart failure (time to the first event), which were assessed by the following indicators: death, sudden death with resuscitation, hospitalization for heart failure, IV introduction of inotropic or vasodilating drugs for 4 or more hours without hospitalization. The death rate from all causes in the valsartan and placebo groups was comparable. Compared with the placebo group, the incidence rate in the group of patients receiving valsartan significantly decreased by 13.2%. The main parameter of effectiveness was a decrease of 27.5% of the time before the 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 heart failure II-IV functional class according to NYHA classification with left ventricular dysfunction (LVEF-40%), the effect of valsartan, in addition to traditional CHF treatment, on exercise tolerance using the Modified Naughton Protocol was evaluated. In all therapeutic groups there was an increase in the time of physical exertion compared to the initial one. Compared to the placebo group, a greater average increase was observed in the patients receiving valsartan from the baseline time of exercise, although this difference was not significant. The most pronounced improvement in exercise tolerance was noted in the subgroup of patients who did not receive ACE inhibitors: the mean change in exercise time in the valsartan group was 2 times greater than that in the placebo group. The effect of valsartan on exercise tolerance versus enalapril (according to a six-minute walking test) was studied in patients with heart failure II-IV functional class according to NYHA classification with left ventricular dysfunction (LVEF? 45%) who received the previous (at least during 3 months) therapy with ACE inhibitors. Patients were transferred from treatment with an ACE inhibitor to either valsartan or enalapril. Valsartan in doses from 80 mg to 160 mg 1 time / day was at least as effective as enalapril in doses from 5 mg to 10 mg 2 times / day.
NYHA class, symptoms, quality of life, ejection fraction. In patients receiving valsartan, there was a significant (in comparison with the placebo group) improvement in the functional class of CHF according to the NYHA classification, as well as signs and symptoms of CHF, incl. such as dyspnea, increased fatigue, peripheral edema, wheezing. In comparison with the placebo group, in patients treated with valsartan, there was a significant increase in the ejection fraction and a significant decrease in LVEF compared with baseline before treatment.
The use of Diovan leads to a reduction in the number of hospitalizations for CHF, slowing the progression of heart failure, improving the functional class of NYHA, increasing the ejection fraction, as well as reducing the signs and symptoms of heart failure and improving quality of life compared with placebo.
Application 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 to 10 days after acute myocardial infarction into groups in which, in addition to traditional treatment, either valsartan (4909 patients) or valsartan and captopril combinations (4,885 patients) or captopril (4909 patients) were initiated.
Death rates for any reason and mortality from specific causes were similar in all three treatment groups. A total of 979 (19.9%) in the combination therapy group died in the valsartan group, 941 (19.3%) and in the captopril group 958 (19.5%). The ratio of the risk of death from cardiovascular causes and the ratio of risk to a composite indicator, including, in addition to cases of cardiovascular death, serious non-fatal cardiovascular events (repeated myocardial infarction, hospitalization due to heart failure, resuscitation after circulatory arrest and stroke) were similar for the valsartan group and captopril group, as well as for the combination therapy group and captopril group.
In the combination therapy group, the greatest incidence of adverse events associated with taking medications has been identified. With monotherapy in the valsartan group, arterial hypotension and renal dysfunction were more common, in the captopril group - cough, rash and taste disorders.
Studies have proven the effectiveness of valsartan, equal to that of captopril, in reducing overall and cardiovascular mortality. The calculated efficacy of valsartan with respect to the effect on the overall mortality rate is 99.6% of that of captopril. Additional analysis, conducted using the placebo-admission method, showed that valsartan reduces the risk of death by 25%.
Valsartan is the same effective drug as captopril in the treatment of patients at high risk of developing cardiovascular complications after myocardial infarction. The addition of valsartan to captopril therapy leads to an increase in the incidence of adverse events, without further improving the survival of patients.
PHARMACOKINETICS
Suction
After taking the drug, suction of valsartan takes place quickly, but the degree of absorption varies widely. The average absolute bioavailability of Diovan is 23%.
In the range of doses studied, the kinetics of valsartan is linear. With repeated use of the drug, no changes in the kinetic parameters were noted.
When appointing Diovan with food, AUC decreases by 48%, although starting from about the 8th hour after taking the drug, the plasma concentrations of valsartan in the group of patients taking it with food and in the group taking on an empty stomach are the same. The decrease in AUC is not accompanied by a clinically significant decrease in the therapeutic effect, so Diovan В® can be administered regardless of food intake.
Distribution
When taking the drug 1 time / day, the cumulation is insignificant. The concentrations of valsartan in the blood plasma in women and men were the same.
Valsartan is bound to a significant extent (by 94-97%) with serum proteins, mainly albumin. V d in the equilibrium state is low (about 17 liters).
Excretion
In comparison with the hepatic blood flow (about 30 l / h) the plasma clearance of valsartan occurs relatively slowly (about 2 l / h). T 1/2 is about 9 hours. The amount of valsartan released with feces is 70% (of the amount taken internally in the dose). With urine output is about 30%, mostly in unchanged form.
Pharmacokinetics in special clinical cases
In some elderly patients, the systemic effect of valsartan was somewhat more pronounced than in young patients, but no clinical significance of this was shown.
There was no correlation between renal function and systemic valsartan, which was to be expected, given that for this substance, the kidney clearance is only 30% of the total clearance value. Therefore, in patients with impaired renal function, dose adjustment is not required. While no studies of the pharmacokinetics of the drug in patients on hemodialysis have been carried out. However, valsartan has a high degree of binding to plasma proteins, so its elimination in hemodialysis is unlikely.
About 70% of the absorbed dose of valsartan is excreted with bile, mostly unchanged. Valsartan does not undergo significant biotransformation, the systemic action of valsartan does not correlate with the degree of hepatic function impairment. Therefore, in patients with hepatic insufficiency 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 liver cirrhosis or biliary tract obstruction, vulsartan AUC increases approximately 2-fold.
INDICATIONS
- arterial hypertension;
- chronic heart failure (II-IV functional class according to NYHA classification) in patients receiving standard therapy, incl. diuretics, digitalis preparations, as well as ACE inhibitors or beta-blockers (not simultaneously). The use of all these drugs is not mandatory;
- to improve the survival of patients with acute myocardial infarction complicated by left ventricular failure and / or left ventricular systolic dysfunction, with stable hemodynamic parameters.
DOSING MODE
Tablets should be taken orally, without chewing.
With arterial hypertension, the recommended dose of Diovan is 80 mg 1 time / day daily, regardless of the race, age and sex of the patient. Antihypertensive effect is observed in the first 2 weeks of treatment; The maximum effect is observed after 4 weeks. Those patients who can not achieve an adequate reduction in blood pressure, a daily dose of Diovan can be increased to 320 mg or additionally prescribed diuretics.
In chronic heart failure, the recommended initial dose of Diovan is 40 mg 2 times / day daily. The dose of Diovan should be gradually increased to 80 mg 2 times / day, and with good tolerability - 160 mg 2 times / day. It may be necessary to reduce the dose of concurrently taken diuretics. The maximum daily dose of Diovan is 320 mg in 2 divided doses.
Evaluation of the condition of patients with chronic heart failure should include an assessment of the state of kidney function.
In the period after myocardial infarction, treatment should be started within 12 hours after myocardial infarction. The initial dose is 20 mg (1/2 tablet 40 mg) 2 times / day. Increasing doses carried by titration (40 mg, 80 mg, 160 mg, 2 times / day) over the next few weeks, until the target dose of 160 mg of 2 times / day. The maximum daily dose of 320 mg in 2 hours. It is usually recommended to achieve a dose of 80 mg of 2 times / day for the second week of treatment. Achieving maximum target dose of 160 mg of 2 times / day is recommended by the end of the third month of therapy Diovanom. Achieving target dose depends on the tolerability of valsartan in the titration period.
In the case of hypotension accompanied by clinical symptoms or impaired renal function, consider a dose reduction.
Assessment of the patients in the period after myocardial infarction should include assessment of renal function.
It does not require correction dosing regimen in patients with impaired renal function and in patients with hepatic insufficiency nebiliarnogo genesis phenomena without cholestasis.
SIDE EFFECT
Has not been shown frequency dependence of any of the adverse effects of the dose or duration of treatment, however undesirable phenomena noted in the application of different doses of valsartan were combined. The frequency of adverse events was also associated with gender, age or race.
Below are all undesirable phenomena observed with a frequency of 1% or more in the group of patients treated with Diovan В® , regardless of their causal relationship to the study drug and post-marketing data obtained in hypertensive patients.
To evaluate the incidence of adverse events, the following criteria: very common (1/10?), Common (1/100 but <1/10?), Sometimes, rarely (1 (1/1000, but <1/100?)? / 10 000, but <1/1000), very rare (<1/10 000).
Infections and infestations: often - viral infections; sometimes - infections of the upper respiratory tract, pharyngitis, sinusitis, fatigue; very rarely - rhinitis.
From hemopoiesis system: often - neutropenia; very rarely - thrombocytopenia.
Immune system: very rarely - hypersensitivity reactions, including serum sickness.
From the side of the central nervous system: often - postural dizziness 2 ; sometimes - vertigo, syncope 1 , insomnia, decreased libido; rarely - dizziness 4 ; very rarely - headache 4 .
From the cardiovascular system: often - orthostatic hypotension 2 ; sometimes - hypotension 1,4 , cardiac insufficiency 1 ; very rarely - vasculitis.
The respiratory system: sometimes - cough.
From the digestive system: sometimes - diarrhea, abdominal pain; very rarely - nausea 4 .
Dermatologic reactions: very rarely - angioedema 3 ; rash, itching.
On the part of the musculoskeletal system: sometimes - pain in the back; very rarely - arthralgia, myalgia.
From the urinary system: very rarely - renal dysfunction 3,4 , acute renal failure 3 , renal insufficiency 3 .
Other: sometimes - fatigue, asthenia, edema, hyperkalemia 1.2 .
Note
1 - data reported adverse events in patients receiving Diovan В® in post-myocardial infarction.
2- Data reported adverse events in patients with CHF receiving Diovan В® .
3 - data reported adverse events with a frequency of "sometimes" in patients receiving Diovan В® in post-myocardial infarction.
4 - more frequently reported adverse events of data in CHF patients receiving Diovan В® (often - dizziness, renal failure, hypotension, and sometimes - headache, nausea).
All patients with chronic heart failure were obtained traditional drug therapy for this disease, which included diuretics, digitalis, beta-blockers or ACE inhibitors.
With prolonged use of valsartan in patients with CHF, additional side effects have been noted.
From the laboratory parameters: seldom - a decrease in hemoglobin concentration and hematocrit. In controlled clinical trials in 0.8% and 0.4% of patients receiving Diovan В® , there was a significant decrease (> 20%) in hemoglobin and hematocrit, respectively. For comparison, in patients treated with placebo, reduced both hematocrit and hemoglobin was noted in 0.1% of cases. Neutropenia was detected in 1.9% of patients receiving Diovan В® , and 1.6% of patients receiving an ACE inhibitor. A significant increase in the concentration of Creatinine, potassium, and total bilirubin in serum was observed, respectively, at 0.8%, 4.4% and 6% of patients treated with DiovanВ® , and 1.6%, 6.4% and 12.9% of patients treated with an ACE inhibitor. In CHF, increased creatinine concentration of greater than 50% was observed in 3.9% of patients treated Diovanom, compared with 0.9% in the placebo group. This increase in potassium level in serum of more than 20% was observed in 10.0% of patients receiving Diovan В® , and 5.1% placebo. In the treatment of patients during the period after myocardial infarction increase in creatinine concentration in the serum 2-fold was observed in 4.2% of patients receiving valsartan, in 4.8% of patients receiving captopril valsartan +, and 3.4% of patients receiving captopril. There have been reports of cases of elevated liver transaminases in patients treated with Diovan В®. Increasing the concentration of urea nitrogen in blood serum for more than 50% was observed in 16.6% of patients treated with valsartan and 6.3 at.% Of patients in the placebo group.
CONTRAINDICATIONS
- Pregnancy;
- lactation period;
- Hypersensitivity to the components of the drug.
With caution should be prescribed with bilateral renal artery stenosis, stenosis of renal artery only, with a diet containing sodium restriction, for conditions involving reduction bcc (including diarrhea, vomiting), against biliary obstruction in hepatic failure, with renal failure (creatinine clearance less than 10 mL / min) (in t. h. patients on hemodialysis).
PREGNANCY AND LACTATION
Given the mechanism of action of angiotensin II, can not eliminate the risk to the fetus. The action of ACE inhibitors (drugs that affect the RAAS) on the fetus in the case of their destination in II and III trimester of pregnancy leads to damage and death.
According to the historical data with the use of ACE inhibitors in the I trimester of pregnancy increases the risk of having children with birth defects. There have been reports of spontaneous abortion, oligohydramnios and renal function in newborns whose mothers during pregnancy inadvertently received valsartan. diovan В®Like any other drug, has a direct impact on the renin-angiotensin-aldosterone system, should not be used during pregnancy and in women planning to become pregnant. In the appointment of drugs acting on the RAAS, the physician should inform women of childbearing age about the potential risk of the negative impact of these drugs on the fetus during pregnancy. If pregnancy is detected during treatment Diovanom, the drug should be discontinued as soon as possible.
It is not known whether valsartan (Diovan active substance) passes into breast milk in humans penetrate, but in experimental models have shown that valsartan is excreted in breast milk. Therefore it is not recommended to use Diovan В® during breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
Patients with impaired renal function changes the dose is not required.
Precautions should be used when Diovan renal failure (creatinine clearance less than 10 mL / min) (in t. H. Patients on hemodialysis).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Patients with liver failure changes the dose is not required if only hepatic failure is not caused or accompanied by cholestasis.
Precautions should be prescribed Diovan in hepatic failure with biliary obstruction.
APPLICATION FOR CHILDREN
Since controlled studies on the effectiveness and safety of valsartan in children and adolescents under the age of 18 years have not been conducted, it is not possible to formulate specific recommendations for use in this patient population.
SPECIAL INSTRUCTIONS
During treatment Diovanom in patients with essential hypertension do not require regular monitoring of laboratory parameters.
Patients with a marked deficiency in the body of sodium and / or BCC, for example, receiving high doses of diuretics, in rare cases, early treatment can occur Diovanom hypotension accompanied by clinical manifestations. Before treatment Diovanom correction should be carried out in the sodium content of the body and / or BCC, for example by reducing the dose of a diuretic.
In the case of hypotension patients should be put, the legs lift and, if necessary, to carry out on / in infusion of 0.9% sodium chloride solution. After the blood pressure has stabilized, the treatment can continue Diovanom.
Application diovan short course of 12 patients with renovascular hypertension, which developed secondary to unilateral renal artery stenosis did not lead to any significant changes in renal hemodynamics concentration of serum creatinine or blood urea nitrogen. However, given that other drugs that affect the renin-angiotensin-aldosterone system may cause an increase in urea and creatinine concentrations in blood serum in patients with unilateral or bilateral renal artery stenosis, as a precaution we recommend a systematic monitoring of these indicators.
Patients with impaired renal function is not required dose correction. However, when expressed violations (where kk is <10 ml / min) caution is recommended.
In patients with hepatic insufficiency do not require dose adjustment, except in cases of cholestasis. Valsartan is derived mostly unchanged in the bile, and it was shown that patients with biliary tract obstruction clearance valsartan reduced. In the appointment of valsartan to these patients should be particularly careful.
In patients with heart failure or post-myocardial infarction, starting treatment Diovanom, often marked by a decrease in blood pressure, and therefore it is recommended to monitor blood pressure at the beginning of therapy. In compliance with recommendations for dosage regimen in the case of significant decrease in blood pressure is generally not required cancellation Diovan.
Because of the inhibition of the renin-angiotensin-aldosterone system in patients with CHF sensitive to changes in renal function. In patients with severe heart failure treatment with ACE inhibitors and angiotensin receptor antagonists may be associated with oliguria and / or increase of azotemia and (rarely) with acute renal failure and / or death. Therefore, an evaluation of the degree of renal function in patients with heart failure and in patients with acute myocardial infarction.
In patients with CHF, caution should be exercised when applying a combination of an ACE inhibitor, a beta-blocker and valsartan.
When hypertension Diovan В® can be administered either as monotherapy or in conjunction with other agents, particularly diuretics.
In CHF Diovan В® can be administered either as monotherapy or in conjunction with other agents - diuretics, digitalis drugs, as well as ACE inhibitors or beta-blockers.
Perhaps the use of Diovan in combination with other drugs administered after myocardial infarction, namely, thrombolytics, aspirin, beta-blockers and statins.
Use in Pediatrics
Since controlled studies on the effectiveness and safety of valsartan in children and adolescents under the age of 18 years have not been conducted, it is not possible to formulate specific recommendations for use in this patient population.
Impact on the ability to drive vehicles and manage mechanisms
In the appointment of Diovan it is recommended to use caution when driving and control mechanism.
OVERDOSE
Symptoms: marked reduction of blood pressure, which can lead to collapse and / or shock.
Treatment: Induce vomiting (if the drug was recently adopted); In marked decrease in blood pressure / are administered in 0.9% sodium chloride solution. Withdrawal of valsartan by hemodialysis is unlikely.
DRUG INTERACTION
Clinically significant interaction Diovan drug В® with other drugs are still noted. Interaction was investigated with the following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine and glibenclamide.
Since Diovan В®is not exposed to any significant metabolism, it is unlikely to clinically significant interactions with other drugs - inducers or inhibitors of cytochrome P450. Despite the fact that valsartan largely bound to plasma proteins, in vitro did not reveal any interaction at this level with a variety of molecules having the same high binding to plasma proteins, such as diclofenac, furosemide and warfarin.
The simultaneous use of potassium-sparing diuretics (e.g., Speer
