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

Excipients: lactose monohydrate (sugar milk) 45 mg, 90 mg or 180 mg; Povidone K-30 (polyvinylpyrrolidone) 2.5 mg, 5 mg or 10 mg; potato starch 27.5 mg, 55 mg or 110 mg; croscarmellose sodium 5 mg, 10 mg or 20 mg; talc 3.75 mg, 7.5 mg or 15 mg; magnesium stearate 1.25 mg, 2.5 mg or 5 mg;

shell: for tablets 40 mg - Opadry® II Pink: hypromellose 1.3600 mg, lactose monohydrate 1,1200 mg, titanium dioxide 1,0348 mg, macrogene 0.4800 mg, iron dye oxide red 0.0036 mg, iron oxide dye yellow 0.0012 mg, indigo carmine aluminum lacquer 0.0004 mg); for tablets 80 mg - Opadry® II Pink: hypromellose 2.7200 mg, lactose monohydrate 2,2400 mg, titanium dioxide 2,0336 mg, macrogol 0.9600 mg, iron oxide red oxide 0.0464 mg); for tablets 160 mg - Opadry^® II Pink: hypromellose 5,4400 mg, lactose monohydrate 4,4800 mg, titanium dioxide 3,4192 mg, macrogol 1,9200 mg, dye crimson [Ponso 4R] 0.6656 mg, quinoline yellow dye 0.0752 mg.

Description:

Round, biconvex tablets, coated with a white film with a pinkish tint of color (for a dosage of 40 mg), or a light pink color (for a dosage of 80 mg) or pink (for a dosage of 160 mg).

On the cross-section the nucleus is white.

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 receptors of the subtype AT₁, which are responsible for the effects of angiotensin II. The consequence of the blockade AT₁ receptors is an increase in plasma concentrations of angiotensin II, which can stimulate blocked 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 likelihood of coughing with valsartan is very low, due to the absence of an 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 during the treatment with an ACE inhibitor,in the treatment of valsartan, this complication was noted in 19.5% of cases, and in the treatment with 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 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 (CHF) is based on its ability to eliminate the negative effects of chronic hyperactivation of the renin-angiotensin-aldosterone system (RAAS) and its main effector, angiotensin II, 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 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 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 plasma.

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 plasma 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 using valsartan with food AUC decreases 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_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:

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 of valsartan is increased by a factor of 2 compared to 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;

- CHF 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 systolic dysfunction of the left ventricle, in the presence of stable indicators of hemodynamics.

Contraindications:

- Hypersensitivity to any of the components of the drug;

- 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;

- age to 18 years;

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the preparation contains lactose).

Carefully:

With bilateral stenosis of the renal arteries; stenosis of the artery of a single kidney; primary hyperaldosteronism; while observing a diet with restriction of consumption of table salt; at conditions accompanied by a decrease in the volume of circulating blood (BCC) (including diarrhea, vomiting); with hepatic insufficiency of mild and moderate severity of non-biliary genesis without the phenomena of cholestasis; with renal insufficiency (creatinine clearance less than 10 ml / min), including patients,who are on hemodialysis (no clinical data); mitral or aortic stenosis, hypertrophic obstructive cardiomyopathy, in patients after kidney transplantation; CHF 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:

The use of the drug is 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, so do not use the drug during breastfeeding.

Dosing and Administration:

Take inside without chewing.

Arterial hypertension

The recommended initial dose of the drug is 80 mg once a day, 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 those patients who can not achieve an adequate therapeutic response, the daily dose of the drug can be increased to a maximum daily dose of 320 mg or diuretics should be additionally applied.

Chronic heart failure

The recommended initial dose is 40 mg twice daily. The dose of the drug 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 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 a day is recommended by the end of the third month of therapy with the drug. 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:

The frequency of side effects was estimated as follows: very often (> 1/10); often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); rarely (> 1/10000, <1/1000); very rarely (<1/10000),the frequency is unknown (the incidence of side effects can not be estimated from the available data).

Patients with hypertension:

Violations of the blood and lymphatic system: frequency unknown - decreased hemoglobin, hematocrit, neutropenia, thrombocytopenia;

Immune system disorders: frequency unknown - hypersensitivity reactions, including serum sickness;

Hearing disorders and labyrinthine disturbances: infrequently - vertigo;

Vascular disorders: frequency unknown - vasculitis;

Disturbances from the respiratory system, organs of the breast gland and mediastinum: infrequently - cough;

Disorders from the gastrointestinal tract: infrequently - vomiting, pain in the abdomen;

Disorders from the liver and bile ducts: frequency unknown - impaired liver function, including increased bilirubin concentration in blood plasma;

Disturbances from the skin and subcutaneous tissues: very rarely - angioedema; skin rash, itching; frequency unknown - bullous dermatitis;

Disturbances from the musculoskeletal and connective tissue: frequency unknown - myalgia;

Disorders from the kidneys and urinary tract: frequency unknown - impaired renal function, increased serum creatinine concentration;

General violations and violations at the place of introduction: infrequently - increased fatigue;

Laboratory and instrumental data: frequency is unknown - an increase in serum potassium, hyponatremia.

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

Violations of the blood and lymphatic system: frequency unknown - thrombocytopenia;

Immune system disorders: frequency unknown - hypersensitivity reactions, including serum sickness;

Metabolic disorders: infrequently hyperkalemia;

Disturbances from the nervous system: often - dizziness, postural dizziness; infrequently - a syncope, a headache;

Hearing disorders and labyrinthine disturbances: infrequently - vertigo;

Heart Disease: infrequently - increased symptoms of CHF;

Vascular disorders: often - marked decrease in blood pressure, orthostatic hypotension; frequency unknown - vasculitis;

Disturbances from the respiratory system of the chest and mediastinum: infrequently - cough;

Disorders from the gastrointestinal tract: infrequently - nausea, diarrhea;

Disturbances from the liver and bile ducts: frequency unknown - impaired liver function;

Disturbances from the musculoskeletal and connective tissue: rarely - rhabdomyolysis, frequency unknown - myalgia;

Disorders from the kidneys and urinary tract: often - impaired renal function; infrequently - acute renal failure, an increase in the concentration of creatinine in the blood plasma; frequency unknown - increase in urea nitrogen in blood plasma;

General violations and violations at the site of introduction: infrequently - asthenia, increased fatigue. Also in clinical trials in patients with arterial hypertension, the following undesirable phenomena were observed, the cause-and-effect relationship with taking the drug was not established:

Impaired nervous system: dizziness;

Disturbances from the respiratory system, chest and mediastinal organs: pharyngitis, rhinitis, sinusitis, upper respiratory tract infections;

Disorders from the gastrointestinal tract: nausea, diarrhea;

Disturbances from the musculoskeletal and connective tissue: arthralgia, back pain;

General violations and violations at the place of introduction: asthenia, insomnia, peripheral edema, decreased libido; viral infections.

Overdose:

Symptoms: In overdose, 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, 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. Recommended control of blood pressure, kidney function and the content of electrolytes in patients taking valsartan 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:

With the simultaneous use of ACE inhibitors and angiotensin II receptor antagonists with lithium preparations, an increase in lithium in the blood plasma and an increase in its toxic effect are noted. Valsartan It is not recommended to use simultaneously with lithium preparations (experience of use is limited). If it is necessary to simultaneously use 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 or potassium-containing salts, can lead to an increase in potassium in the blood plasma and in patients with heart failure to increase the concentration of creatinine in the blood plasma.If such combination treatment is considered necessary, care should be taken.

Protein vectors:

By the results of the study in vitro on liver cultures valsartan is a substrate for OAT31B1 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 increase the systemic exposure of valsartan (C_mOh and AUC).

Special instructions:

Deficiency in the body of sodium and / or decrease in 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 the drug may occur arterial hypotension, accompanied by clinical manifestations. Before beginning treatment with the drug should be corrected the content 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 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 levels in blood plasma should be performed.

Stenosis of the renal artery:

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

Impaired renal function:

Patients with impaired renal function do not need a dose adjustment.However, with pronounced impairment of kidney function (when the SC 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 valsartan in patients who undergone 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 the drug, these patients should be very careful.

Quincke's Edema:

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.Admission of the drug in the case of the development of edema Quincke should be immediately canceled, the resumption of the drug 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.

Chronic heart failure / period after myocardial infarction:

In patients with CHF or after a myocardial infarction, starting treatment with the drug, there is often a slight decrease in blood pressure, and therefore 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 discontinue the drug 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 AH1F inhibitors and angiotensin II receptor antagonists may be accompanied by oliguria and / or augmentation of azotemia and (rarely) acute renal failure and / or fatal.Therefore, in these categories of patients before the use of the drug, and also periodically during therapy with the drug, it is necessary to assess the function of the kidneys.

Combination therapy with arterial hypertension:

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

Combined therapy in the post-myocardial infarction period:

It is possible to use the drug 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, the use of the drug is not recommended simultaneously 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 for CHF:

With CHF, the drug 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-blocker and valsartan.

Aortic and mitral stenosis. Obstructive hypertrophic cardiomyopathy:

As with other vasodilating agents, caution should be exercised when taking Valsartan MC in patients with aortic and mitral stenosis and obstructive hypertrophic cardiomyopathy.

Pregnancy:

The intake of angiotensin II receptor antagonist is contraindicated during pregnancy. Patients planning pregnancy should choose treatment with alternative drugs that have a confirmed safety profile during pregnancy. If pregnancy is diagnosed during treatment with Valsartan MS, it should be canceled as soon as possible and an alternative treatment is prescribed.

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:

For 7 or 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 30, 50, 60 or 100 tablets in cans of polymeric.

Each bank or 2, 3, 4 contour cell packs of 7 tablets or 1, 3, 5, 6, 10 contour cell packs of 10 tablets with instructions for use are placed in a pack of cardboard.

Storage conditions:

In a dry, protected from light place, at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004022

Date of registration:22.12.2016

Expiration Date:22.12.2021

The owner of the registration certificate:MEDISORB, CJSC MEDISORB, CJSC Russia

Manufacturer: & nbsp

MEDISORB, CJSC Russia

Information update date: & nbsp20.01.2017

Illustrated instructions

Instructions

Valsartan MS (Valsartan MS)