Valsartan - instructions for use, dose, side effects, contraindications

Active substance:
Valsartan	40.0 mg	80.0 mg	160.0 mg
Excipients (core):
Microcrystalline cellulose	45.1 mg	90.20 mg	180.4 mg
Croscarmellose sodium	2.75 mg	5.50 mg	11.0 mg
Silica colloidal dioxide	1.35 mg	2.70 mg	5.4 mg
Magnesium stearate	0.80 mg	1.60 mg	3.2 mg
Auxiliary substances (shell):
Opadrai Pink in t.ch.	3.00 mg	6.0 mg	12.0 mg
Polyvinyl alcohol	1.20 mg	2.4 mg	4.8 mg
Macrogol-3350	0.731 mg	1.463 mg	2.926 mg
Iron Oxide Red Dye Oxide	0.012 mg	0.024 mg	0.048 mg
Dye iron oxide yellow	0.007 mg	0.013 mg	0.026 mg
Talc	0.444 mg	0.888 mg	1.776 mg
Titanium dioxide	0.606 mg	1.212 mg	2.424 mg

Description:

Round tablets of biconvex form, covered with a film coat of light pink color, on the fracture are visible two layers - a core of white or almost white color and a film membrane. Tablets with a dosage of 40 and 80 mg with a risk on one side.

Pharmacotherapeutic group:Angiotensin II receptor antagonist

ATX: & nbsp

C.09.C.A.03 Valsartan

C.09.C.A Angiotensin II antagonists

Pharmacodynamics:

Valsartan is an active specific antagonist of angiotensin II receptors, intended for oral administration. Selectively blocks AT receptor subtype₁, which are responsible for the effects of angiotensin II. The consequence of the blockade of AT₁-receptors is an increase in the plasma concentration of angiotensin II, which can stimulate unlocked AT₂-receptors. Valsartan does not have any expressed agonistic activity against AT₁receptors. The affinity of valsartan for the receptors of the subtype AT₁ approximately 20,000 times higher than to the AT subtype receptors₂.

The probability of occurrence of cough in the application of valsartan is very low, due to the lack of effect on angiotensin converting enzyme (ACE), which is responsible for the degradation of bradykinin. A comparison of valsartan with an ACE inhibitor showed that the incidence of dry cough was significantly (p <0.05) lower in patients who received valsartan, than in patients receiving an ACE inhibitor (2.6% vs. 7.9%, respectively). In a group of patients who previously developed a dry cough in the treatment with an ACE inhibitor, this complication was observed in 19.5% of cases with valsartan and in 19.0% of cases with a thiazide diuretic, 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 that are important for the regulation of cardiovascular functions.In the treatment of valsartan in patients with arterial hypertension, there is a decrease in blood pressure (BP), not accompanied by a change in the heart rate (heart rate).

After ingestion of a single dose of the drug in most patients, the onset of 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. With repeated prescriptions of the drug, the maximum reduction in blood pressure, regardless of the dose taken, is usually achieved within 2-4 weeks and is 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. A sharp discontinuation of valsartan is not accompanied by a sharp increase in blood pressure or other undesirable consequences.

The mechanism of action of valsartan in chronic heart failure 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,- 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, etc.). Against the background of valsartan in chronic heart failure (CHF), prednagruzka decreases, the wedging pressure in the pulmonary capillaries (DZLK) decreases and the diastolic pressure in the pulmonary artery increases, cardiac output increases. Along with hemodynamic effects, valsartan due to 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.

Pharmacokinetics:

Valsartan is rapidly absorbed after ingestion, but the degree of absorption varies widely. The average absolute bioavailability of valsartan is 23%. The time required to reach the maximum concentration (TC_mOh) - 2 hours.After regular use, the maximum decrease in blood pressure develops after 4 weeks. When using the drug once a day, its cumulation is insignificant. The concentration of valsartan in the blood plasma is the same for men and women.

Valsartan actively binds to blood serum proteins (94-97%), mainly with albumin. The volume of distribution of valsartan is small, about 17 liters. Plasma clearance is relatively low (approximately 2 liters / hour) when compared with hepatic blood flow (approximately 30 liters / hour).

Valsartan does not undergo a pronounced metabolism (about 20% of the dose is determined in the form of metabolites). The hydroxyl metabolite is determined in blood plasma at low concentrations (less than 10% of the area under the concentration-time curve (AUC) valsartan). This metabolite is pharmacologically inactive. Valsartan biphasic: an alpha phase with a half-life of less than 1 hour and a beta phase with a half-life of about 9 hours.

Displayed valsartan mainly in unchanged form through the intestine (about 83%) and kidneys (about 13%). The half-life (T_1/2) of valsartan is 6 hours.

When valsartan is used with food, the area under the concentration-time curve decreases (AUC) by 48%.Nevertheless, 8 hours after the application of the drug, the concentration of valsartan in blood plasma, taken on an empty stomach and with food, is the same. Decrease AUC is not accompanied by a clinically significant decrease in the therapeutic effect of valsartan, so the drug can be used both before and after meals.

Pharmacokinetics in specific patient groups

Patients with CHF

In this category of patients, TC_mOh and T_1/2similar to those of healthy volunteers. Increase AUC and C_mOh is directly proportional to the increase in the dose of the drug (from 40 mg to 160 mg 2 times / day). The cumulation factor averages 1.7. When administered, the clearance of valsartan was approximately 4.4 liters / hour. The age of patients with CHF did not affect the clearance of valsartan.

Patients over the age of 65 years

In some patients over the age of 65, systemic bioavailability of valsartan is higher than that of young patients, but there is no clinical significance.

Patients with impaired renal function

Correlation between renal function and systemic bioavailability of valsartan is absent. In patients with impaired renal function and creatinine clearance (CK) of more than 10 ml / min, dose adjustment is not required.At present, there are no data on the use in patients on hemodialysis. Valsartan has a high degree of binding to blood plasma proteins, so its elimination by hemodialysis is unlikely.

Patients with impaired hepatic function

In patients with mild and moderate impairment of liver function, increased bioavailabilityAUC) valsartan in 2 times in comparison with healthy volunteers. However, there is no correlation of the values AUC Valsartan with a degree of impaired liver function. The use in patients with severe impairment of liver function has not been studied.

Indications:

- Arterial hypertension;

- chronic heart failure in patients receiving standard therapy with one or more drugs: diuretics, cardiac glycosides, ACE inhibitors or beta-blockers. The use of each of these drugs is not mandatory;

- to improve the survival of patients after acute myocardial infarction complicated by left ventricular failure and / or left ventricular systolic dysfunction, with stable hemodynamic parameters.

Contraindications:

- Hypersensitivity to any component of the drug;

- pregnancy, pregnancy planning;

- lactation period;

- age to 18 years;

- severe violations of the liver (more than 9 points on the scale Child-Pugh), biliary cirrhosis and cholestasis;

- simultaneous use of antagonists of angiotensin receptors II, including valsartan, or ACE inhibitors with aliskiren in patients with diabetes mellitus.

Carefully:

With bilateral renal artery stenosis, stenosis of the artery of a single kidney, primary hyperaldosteronism, with a diet with restriction of consumption of table salt, in conditions accompanied by a decrease in the volume of circulating blood (bcc) (including diarrhea, vomiting), with mild to moderate hepatic insufficiency the severity of non-biliary origin without the phenomena of cholestasis, with renal insufficiency (creatinine clearance less than 10 ml / min), including patients on hemodialysis (no clinical data), valsartan should be administered with caution; mitral or aortic stenosis, hypertrophic obstructive cardiomyopathy, in patients after kidney transplantation.Chronic heart failure II-IV functional class by classification NYHA; simultaneous use of angiotensin II receptor antagonists, including valsartan, with other agents that inhibit RAAS, such as ACE inhibitors, etc.

It is not recommended to apply valsartan concurrent with ACE inhibitors, since this combination therapy has no advantage over monotherapy with valsartan or an ACE inhibitor for overall mortality rates for any reason.

Pregnancy and lactation:

Application of the drug Valsartan contraindicated during pregnancy.

Given the mechanism of action of angiotensin II receptor antagonists, the risk to the fetus can not be ruled out. The effect of ACE inhibitors (drugs that affect RAAS) on the fetus, in case of their appointment in the second and third trimesters of pregnancy, leads to its damage and death. According to the retrospective data, when using ACE inhibitors in the first trimester of pregnancy, the risk of having children with congenital defects increases. There are reports of spontaneous abortions, oligohydramnios and renal dysfunction in newborns whose mothers were unintentionally receiving valsartan. Valsartan, like any other drug that directly affects RAAS, should not be used in pregnancy, as well as in women planning pregnancy. When using agents that affect RAAS, the doctor should inform women of childbearing age of the potential risk of adverse effects of these drugs on the fetus during pregnancy.

If pregnancy is detected during treatment with Valsartan, the drug should be discontinued as soon as possible.

It is not known whether valsartan in breast milk. Therefore, do not use the drug Valsartan during lactation.

Dosing and Administration:

Tablets are taken orally, without chewing.

Arterial hypertension

The recommended initial dose of the drug Valsartan is 80 mg once a day daily, regardless of race, age and sex of the patient.

Antihypertensive effect develops in the first 2 weeks of treatment; The maximum effect is observed after 4 weeks. For patients who do not achieve an adequate therapeutic response, the daily dose of the drug Valsartan can be increased to a maximum daily dose of 320 mg, or diuretics should be used additionally.

Chronic heart failure

The recommended initial dose of the drug Valsartan is 40 mg 2 times a day daily. Dose of the drug Valsartan should be gradually increased for at least 2 weeks to 80 mg twice a day, and with good tolerability - up to 160 mg 2 times a day. It may be necessary to reduce the dose of concurrently taken diuretics. The maximum daily dose of the drug Valsartan is 320 mg in 2 divided doses.

To improve survival after a previous 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 a day. The dose is increased by titration (40 mg, 80 mg, 160 mg twice daily) for several consecutive weeks, until the target dose of 160 mg twice a day is reached. The maximum daily dose is 320 mg in 2 divided doses. Usually, it is recommended to achieve a dose of up to 80 mg twice a day by the end of the second week of treatment. Achievement of the maximum target dose of 160 mg 2 times per day is recommended by the end of the third month of therapy with the drug Valsartan. The increase in dose depends on the tolerability of the drug during the titration period.

In the case of development of arterial hypotension, accompanied by clinical manifestations, or renal dysfunction should consider the possibility of dose reduction. Evaluation of the condition of patients in the post-myocardial infarction period should include assessment of renal function.

Use in patients over the age of 65 years

In elderly patients, dose adjustment is not required.

Patients with impaired renal function

In patients with impaired renal function, dose adjustment is not required. Currently, there are no clinical data on the use of the drug in patients with SC less than 10 ml / min.

Patients with hepatic impairment

Patients with mild or moderate impairment of non-biliary liver function without the phenomena of cholestasis should be used with caution, the daily dose should not exceed 80 mg.

Side effects:

Frequency of side effects: "very often" (1/10 or more); "often" (1/100 or more, less than 1/10); "infrequently" (1/1000 and more, less than 1/100); "rarely" (1/10000 or more, less than 1/1000), "very rarely" (less than 1/10000). For all undesirable phenomena,revealed in clinical practice and in the analysis of laboratory indicators (the frequency of development of which can not be established) was used gradation "frequency is unknown."

Patients with hypertension

On the part of the hematopoiesis system: the frequency is unknown - a decrease in hemoglobin, hematocrit, neutropenia, thrombocytopenia.

From the immune system: frequency is unknown - hypersensitivity reactions, including serum sickness.

Metabolic disorders: the frequency is unknown - an increase in the potassium content in the serum.

From the hepatobiliary system: frequency unknown - impaired liver function, including increased bilirubin concentration in blood plasma.

From the side of the hearing organ and labyrinthine disorders: infrequently - vertigo.

From the cardiovascular system: frequency is unknown - vasculitis.

From the respiratory system: infrequently - cough.

From the gastrointestinal tract: infrequently - pain in the abdomen.

From the skin and subcutaneous tissue: very rarely - angioedema; skin rash, itching.

From the musculoskeletal system: frequency is unknown - myalgia.

From the side of the kidneys: frequency unknown - renal dysfunction, increased serum creatinine concentration.

Other: infrequently - increased fatigue.

Also, in clinical trials in patients with hypertension, the following adverse events were observed, a cause-and-effect relationship with the drug was not established: arthralgia, asthenia, back pain, diarrhea, dizziness, insomnia, decreased libido, nausea, peripheral edema, pharyngitis, rhinitis, sinusitis, upper respiratory tract infections, viral infections.

Patients who received the drug after a previous myocardial infarction and / or CHF

On the part of the hematopoiesis system: frequency unknown - thrombocytopenia.

From the immune system: frequency is unknown - hypersensitivity reactions, including serum sickness.

Metabolic disorders: infrequently hyperkalemia.

From the nervous system: often - dizziness, postural dizziness; infrequently - a syncope, a headache.

From the side of the hearing organ and labyrinthine disorders: infrequently - vertigo.

From the cardiovascular system: often - marked decrease in blood pressure, orthostatic hypotension; infrequently - increased symptoms of CHF; frequency is unknown - vasculitis.

From the respiratory system: infrequently - cough.

From the gastrointestinal tract: infrequently - nausea, diarrhea.

From the musculoskeletal system: rarely - rhabdomyolysis, the frequency is unknown - myalgia.

From the side of the kidneys: often - impaired renal function; infrequently - acute renal failure, increased serum creatinine concentration; frequency is unknown - an increase in the urea nitrogen in the blood plasma.

Common violations: infrequently - asthenia, increased fatigue.

From the hepatobiliary system: frequency unknown - impaired liver function.

Overdose:

Symptoms: with an overdose of the drug Valsartan the main manifestation is a marked decrease in blood pressure, which can lead to depression, collapse and / or shock.

Treatment: Symptomatic, the nature of which depends on the time elapsed since the time of taking the drug, and on the severity of the symptoms. In case of accidental overdose, you should induce vomiting (if the drug is taken recently) or to wash the stomach.With a marked decrease in blood pressure, the usual method of therapy is the intravenous injection of a 0.9% solution of sodium chloride, the patient should be laid, raising his legs, for a period of time necessary for therapy, to take active measures to maintain the cardiovascular system, including regular monitoring of heart activity and respiratory systems, the volume of BCC and the amount of excreted urine.

It is unlikely that valsartan can be removed from the body by hemodialysis.

Interaction:

Double blockade of RAAS in the use of angiotensin receptor antagonists II, ACE inhibitors or aliskiren

Simultaneous use of angiotensin II receptor antagonists, including valsartan, with other drugs that affect RAAS, is associated with an increased incidence of arterial hypotension, hyperkalemia and renal dysfunction compared with monotherapy. It is recommended to control blood pressure, kidney function and electrolyte content in patients taking valsartan and other drugs that affect RAAS.

It was found that with monotherapy valsartan there are no clinically significant interactionswith the following medicinal products: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine and glibenclamide.

Non-steroidal anti-inflammatory drugs (NSAIDs): when used simultaneously with NSAIDs (including selective inhibitors of cyclooxygenase-2 (COX-2)), a decrease in the antihypertensive effect of valsartan is possible. When angiotensin II receptor antagonists are used concomitantly with NSAIDs, kidney function may worsen and potassium levels rise in the blood plasma. If it is necessary to simultaneously use valsartan and NSAIDs before starting therapy, it is necessary to evaluate the kidney function and correct the disturbances of the water-electrolyte balance.

Lithium preparations: with concomitant use of ACE inhibitors and angiotensin II receptor antagonists, an increase in lithium content in the blood plasma and an increase in its toxic effect are observed simultaneously with lithium preparations. Valsartan It is not recommended to use simultaneously with lithium preparations (experience of use is limited). If it is necessary to simultaneously apply the drug Valsartan and lithium preparations, it is necessary to control the lithium content in the blood plasma.

Preparations of potassium: simultaneous use of potassium-sparing diuretics (including spironolactone, triamterene, amiloride), potassium salts or formulations containing potassium, may lead to an increase of potassium in blood serum and in patients with heart failure increases the concentration of serum creatinine. If such combination treatment is considered necessary, care should be taken.

Protein-carriers

By the results of the study in vitro on liver cultures valsartan is a substrate for the OATP1B1 carrier proteins and MRP2. Simultaneous administration of valsartan with inhibitors of the carrier protein OATP1B1 (rifampicin, ciclosporin) and with an inhibitor of carrier protein MRP2 (ritonavir) can damage the systemic exposure of valsartan (C_mOh and AUC).

Special instructions:

Deficiency in the body of sodium and / or a decrease in the volume of circulating blood (BCC)

In patients with severe sodium deficiency and / or reduced bcc, such as those receiving high doses of diuretics, in rare cases at the beginning of treatment with the drug Valsartan can occur arterial hypotension, accompanied by clinical manifestations. Before starting treatment with the drug Valsartan should correct the content in the body of sodium and / or BCC, including by reducing the dose of the diuretic.

In case of development of arterial hypotension, the patient should be laid, legs elevated. If necessary, an intravenous infusion of 0.9% solution of sodium chloride. After the BP stabilizes, the drug treatment Valsartan can continue.

Hyperkalemia

When used simultaneously with dietary supplements containing potassium, potassium-sparing diuretics, potassium-containing salt substitutes, or with other medicines that can cause hyperkalemia (for example, with heparin), care should be taken and regular monitoring of potassium in the blood.

Stenosis of the renal artery

Application of the drug Valsartan short course in patients with reninvascular hypertension that developed secondary due to unilateral stenosis of the renal artery did not lead to any significant changes in renal hemodynamics, serum creatinine concentration, or blood urea nitrogen.However, given that other drugs that affect RAAS can cause an increase in serum urea and creatinine levels in patients with bilateral or unilateral stenosis of the renal artery, it is recommended to monitor these indicators as a precautionary measure.

Renal impairment

Patients with impaired renal function do not need a dose adjustment. However, with pronounced violations of kidney function (when creatinine clearance is less than 10 ml / min), caution is recommended. Avoid simultaneous use of angiotensin II receptor antagonists, including valsartan, or ACE inhibitors with aliskiren in patients with severe renal dysfunction (CC less than 30 ml / min).

Kidney Transplantation

Data on the safety of the drug Valsartan patients who have undergone kidney transplantation do not.

Impaired liver function

Patients with hepatic insufficiency do not need a dose adjustment, except for cases of cholestasis. Valsartan is mainly excreted unchanged with bile through the intestine, and it has been shown that in patients with bile duct obstruction the valsartan clearance is reduced. When the drug is prescribed Valsartan these patients should be very careful.

Edema Quincke

Quincke's edema, including the larynx and vocal cords leading to airway obstruction, and / or edema of the face, lips, pharynx and / or tongue edema, occurred in patients who received valsartan, some of these patients previously developed Quincke's edema on the background of taking other drugs, including ACE inhibitors. Reception of the drug Valsartan In case of development of the edema Quincke should be immediately canceled, the resumption of the drug Valsartan forbidden.

Primary hyperaldosteronism

The drug is ineffective for the treatment of hypertension in patients with primary hyperaldosteronism, since this category of patients does not have activation of RAAS.

CHF / period after a previous myocardial infarction

In patients with CHF or after a previous myocardial infarction, starting treatment with the drug Valsartan, often there is a slight decrease in blood pressure, in this connection, it is recommended to monitor BP at the beginning of therapy. Subject to the recommendations on the dosing regimen, there is usually no need to abolish Valsartan because of hypotension.Evaluation of patients with CHF should include assessment of renal function.

Due to inhibition of RAAS in some patients, renal dysfunction may occur. In patients with CHF II-IV functional class by classification NYHA treatment with ACE inhibitors and angiotensin II receptor antagonists may be accompanied by oliguria and / or increased azotemia and (rarely) acute renal failure and / or fatal. Therefore, in these categories of patients before using the drug Valsartan, and also periodically during therapy with the drug, it is necessary to assess the function of the kidneys.

Combination therapy for hypertension

With arterial hypertension, the drug Valsartan can be used in monotherapy, as well as simultaneously with other antihypertensive drugs.

Combination therapy in the post-myocardial infarction period

Possible use of the drug Valsartan in combination with other drugs used after a myocardial infarction, namely: thrombolytics, acetylsalicylic acid as an antiplatelet agent, beta-adrenoblockers and inhibitors of HMG-CoA reductase (statins).

In this category of patients it is not recommended to use the drug Valsartan concurrent with ACE inhibitors, since this combination therapy has no advantage over monotherapy with valsartan or an ACE inhibitor for overall mortality rates for any reason.

Combination therapy with CHF

With CHF, the drug Valsartan can be used both in monotherapy and simultaneously with other drugs - diuretics, cardiac glycosides, as well as ACE inhibitors or beta-blockers.

In this category of patients is not recommended the use of triple combination therapy of ACE inhibitors, beta-adrenoblocker and drug Valsartan.

Effect on the ability to drive transp. cf. and fur:

They are used with caution in patients who drive vehicles and engage in activities requiring increased attention and speed of motor and mental reactions (risk of developing dizziness or fainting).

Form release / dosage:

Film-coated tablets, 40 mg, 80 mg and 160 mg.

Packaging:

By 7, 10, 14, 20, 28, 30, 56 tablets into a contour mesh box made of polyvinyl chloride film and aluminum foil printed lacquered.

By 7, 10, 14, 20, 28, 30, 40, 50 or 100 tablets in cans of polymeric for medicines.

One jar or 1, 2, 3, 4, 5, 6, 8 or 10 contour squares, together with the instructions for use, are placed in a cardboard package (bundle).

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002325

Date of registration:09.12.2013

Expiration Date:09.12.2018

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Representation: & nbspOZONE LLC OZONE LLC Russia

Information update date: & nbsp20.01.2017

Illustrated instructions

Instructions

Valsartan (Valsartan)