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

Active substance:
Valsartan	20.0 mg	40.0 mg	80.0 mg	160.0 mg
Excipients:
Microcrystalline cellulose	152.7 mg	131.5 mg	89.1 mg	178.2 mg
Croscarmellose sodium	3.6 mg	3.6 mg	3.6 mg	7.2 mg
Povidone-K17	0.75 mg	1.5 mg	3.0 mg	6.0 mg
Silica colloidal dioxide	1.35 mg	1.8 mg	2.7 mg	5.4 mg
Magnesium stearate	1.6 mg	1.6 mg	1.6 mg	3.2 mg
Capsules hard gelatinous №2, №0
Capsule composition:
Housing:
Iron Oxide Dye Oxide	_	_	_	0,01%
Iron Oxide Red Dye Oxide	-	0,008%	-	0,01%
Dye iron oxide yellow	0,1763%	0,2727%	0,1763%	0,1714%
Titanium dioxide	0,9744%	2%	0,9744%	3%
Gelatin	up to 100%	up to 100%	up to 100%	up to 100%
Cap:
Iron Oxide Dye Oxide	-	-	-	0,01%
Iron Oxide Red Dye Oxide	0,008%	0,008%	-	0,01%
Dye iron oxide yellow	0,2727%	0,2727%	0,1763%	0,1714%
Titanium dioxide	2%	2%	0,9744%	3%
Gelatin	up to 100%	up to 100%	up to 100%	up to 100%

Description:

Dosage of 20 mg. Capsules hard gelatinous № 2. The case of light yellow color with a beige shade, a cover of light yellow color with a creamy shade opaque.

The dosage is 40 mg. Capsules hard gelatinous № 2. The case and a cover of light yellow color with a cream shade opaque.

Dosage of 80 mg. Capsules hard gelatinous № 2. The case and a cover of light yellow color with a beige shade opaque.

Dosage of 160 mg. Capsules hard gelatinous № 0. The case and a cover of light brown color opaque.

The contents of the capsules are a mixture of powder and granules of white or almost white color.It is possible to compact the contents of the capsules into lumps in the shape of a capsule, which are easily disintegrated when pressed.

Pharmacotherapeutic group:angiotensin II receptor antagonist

ATX: & nbsp

C.09.C.A.03 Valsartan

C.09.C.A Angiotensin II antagonists

Pharmacodynamics:

Valsartan - active specific antagonist of angiotensin II receptors, intended for oral administration. Selectively blocks receptors of the subtype AT₁, which are responsible behind effects of angiotensin II. The consequence of the blockade 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 in relation to 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 reliably (p < 0.05) is lower in patients who received valsartanthan the of 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 decrease in blood pressure,regardless of the dose taken, 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. 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 drug is administered, the concentration of valsartan in 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_max and T_1/2similar to those of healthy volunteers. Increase in AUC and C_max 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, however, 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, the bioavailability (AUC) of valsartan is increased by a factor of 2 compared to healthy volunteers. However, there is no correlation between valsartan AUC values and the degree of hepatic impairment.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 angiotensin II receptor antagonists, including valsartan, or ACE inhibitors with aliskiren in patients with diabetes mellitus.

Carefully:

With bilateral stenosis of the renal arteries, 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 (including bovine blood) (including diarrhea, vomiting), with mild to moderate liver failure of non-biliary origin without cholestasis, in 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 Sartavel® contraindicated during pregnancy.

Given the mechanism of action of angiotensin receptor antagonists II, you can not exclude the risk to the fetus. 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. Sartavel®, 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 Sartavel®, the drug should be discontinued as soon as possible.

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

Dosing and Administration:

Capsules should be taken orally, without chewing.

Arterial hypertension

The recommended initial dose of the drug Sartavel® 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 Sartavel® 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 Sartavel® is 40 mg 2 times a day daily. The dose of the drug Sartavel® 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 Sartavel® 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 twice 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 Sartavel®. 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 the undesirable phenomena found in clinical practice and in the analysis of laboratory indicators (the frequency of development of which can not be established), the gradation "frequency unknown" was used.

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: frequency unknown - increase of potassium content in blood serum.

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

Co the sides of the hearing organ and labyrinthine disorders: infrequently - vertigo.

Co cardiovascular system: frequency is unknown - vasculitis.

Co of the respiratory system: infrequently - cough.

Co side of the gastrointestinal tract: infrequently - pain in the abdomen.

From the skin and subcutaneous tissue: rarely - angioedema; skin rash, itching; frequency unknown - bullous dermatitis.

Co of 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 - fainting, headache.

Co hand body hearing and labyrinthine disorders: infrequently - vertigo.

From the side of the cardiovascular system: often - marked decrease in blood pressure, orthostatic hypotension; infrequently - increased symptoms of CHF; frequency 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 unknown - increase in the content of urea nitrogen in the blood plasma.

Common violations: infrequently - asthenia, increased fatigue.

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

Overdose:

Symptoms: when an overdose of the drug Sartavel ® 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 an intravenous injection of 0.9% sodium chloride solution, the patient should be laid, lifting his legs, on necessary for the therapy period of time, to take active measures to support the activity of the cardiovascular system, including regular monitoring of the heart and respiratory system, the volume of BCC and the amount of urine released.

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

Interaction:

Double blockade of RAAS with angiotensin II receptor antagonists,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 the drug Sartavel® and other drugs that affect RAAS.

It was found that with monotherapy valsartan there are no clinically significant interactions with the following drugs: 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: while the use of ACE and angiotensin II receptor antagonists, inhibitors simultaneously with drugs lithium marked increase lithium content in the blood plasma and increased its toxic actions Sartavel® not recommended to use simultaneously with lithium drugs (application experience is limited). If it is necessary to simultaneously use the drug Sartavel® 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 carrier proteins OATP1B1 and MRP2. Simultaneous administration of valsartan with inhibitors of the carrier protein OATP1B1 (rifampicin, ciclosporin) and with an inhibitor of the transporter protein MRP2 (ritonavir) can damage the system exposure of Sartavel® (C_max 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 deficiency in the body of sodium and / or reduced bcc, for example, receiving high doses of diuretics, in rare cases at the beginning of treatment with Sartavel®, arterial hypotension may occur, accompanied by clinical manifestations. Before starting treatment with Sartavel ®, you should correct the sodium and / or BCC content, 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 BP stabilizes, treatment with Sartavel® can be continued.

Hyperkalemia

With simultaneous application with biologically active additives containing potassium,potassium-sparing diuretics, potassium-containing salt substitutes, or with other medicines that can cause hyperkalemia (eg, with heparin), care should be taken and regular monitoring of potassium in the blood.

Stenosis of the renal artery

The use of the Sarthavel® preparation in a short course in patients with reninvascular hypertension, which developed again 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 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 severe renal dysfunction (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

There are no data on the safety of the use of Sartavel® in patients who underwent kidney transplantation.

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 prescribing Sartavel®, 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. Taking Sarthavel® in case of development of Quincke's edema should be immediately canceled, resumption of Sarthavel® preparation is prohibited.

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 Sartavel®, 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 dosing regimens, there is usually no need to cancel Sartavel® due to 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 Sartavel®, 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

It is possible to use the drug Sartavel® in combination with other drugs used after myocardial infarction, namely thrombolytics, acetylsalicylic acid as antiplatelet agent, beta-adrenoblockers and inhibitors of HMG-CoA reductase (statins).

In this category of patients it is not recommended to use the drug Sartavel® 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 Sartavel® 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 Sartavel®.

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:

Capsules, 20 mg, 40 mg, 80 mg and 160 mg.

Packaging:

10, 20, 30 capsules in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 10, 20, 30, 40, 50 or 100 capsules in cans of polymeric for medicines.

One jar or 1, 2, 3, 4, 5, 10 contour mesh packages together with the instruction 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

Obsolete name of the trade product: & nbspValsartan

Date renamed: & nbsp15.07.2014

Registration number:LP-002327

Date of registration:11.12.2013

Expiration Date:11.12.2018

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

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp06.12.2015

Illustrated instructions

Instructions

Sartavel® (Sartavel®)