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

core: (mixture of microcrystalline cellulose 98% and colloidal dioxide 2% silicon dioxide), 33.5 mg, sorbitol 9.25 mg, magnesium carbonate 90 (90% magnesium carbonate mixture, pregelatinized starch 9% and water 1%) 9, 25 mg, corn pregelatinized corn starch - 3 mg, povidone K-25 - 7.5 mg, sodium stearyl fumarate - 4 mg, sodium lauryl sulfate - 1 mg, crospovidone Type A - 13 mg, silicon dioxide colloidal anhydrous - 2 mg;

film sheath: Opadrai® OY-L-28900 (mixture of lactose monohydrate 36%, hypromellose 2910 28%, titanium dioxide 26% and macrogol 10%) - 3 mg, ferric oxide red oxide - 0.2 mg.

Tablets 160 mg

active substance: valsartan - 160 mg;

Excipients:

core: (mixture of microcrystalline cellulose 98% and colloidal dioxide 2% silica) 67 mg, sorbitol 18.5 mg, magnesium carbonate 90 (magnesium carbonate 90%, pregelatinized starch 9% and water 1%) 18.5 mg , corn pregelatinized corn starch - 6 mg, povidone K-25 - 15 mg, sodium stearyl fumarate - 8 mg, sodium lauryl sulfate - 2 mg, crospovidone Type A - 26 mg, silicon dioxide colloidal anhydrous - 4 mg;

film sheath: Opadrai® OY-L-28900 (mixture of lactose monohydrate 36%, hypromellose 2910 28%, titanium dioxide 26% and macrogol 10%) - 6 mg, iron oxide oxide yellow 0.4 mg,ferric oxide brown oxide 0.1 mg.

Description:

Tablets 80 mg: round biconvex tablets, covered with a film shell of dark pink color, with a risk on one side. The core on the transverse section is white or almost white.

Tablets 160 mg: round biconvex tablets covered with a film coating of a brownish-yellow color, with a risk on one side. The core on the transverse section is white or almost white.

Pharmacotherapeutic group:Angiotensin II receptor antagonist

ATX: & nbsp

C.09.C.A.03 Valsartan

C.09.C.A Angiotensin II antagonists

Pharmacodynamics:

Specific antagonist of angiotensin II receptors. Selectively blocks receptors of the subtype AT₁, which are responsible for the known 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 AT subtype receptors₁ approximately 20,000 times higher than to the AT subtype receptors₂.

The likelihood of coughing with valsartan is very low, due to the lack of influence on the angiotensin-converting enzyme (ACE),kininase II, which is responsible for the degradation of bradykinin.

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.

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 valsartan is not accompanied by a sharp increase in blood pressure or other undesirable clinical 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). 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.

Pharmacokinetics:

Suction:

After taking the drug, suction of valsartan takes place quickly, but the degree of absorption varies widely. The average absolute bioavailability 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. Food reduces the effect of valsartan by approximately 40% and the maximum concentration in the blood plasma (C_mOh) by approximately 50%, although approximately 8 hours after taking a dose of valsartan in the blood plasma in the food group and in the fasting group were the same. However, this decrease in concentration is not accompanied by a clinically significant decrease in the therapeutic effect, therefore valsartan can be administered regardless of the meal.

Distribution

The volume of distribution of valsartan in the equilibrium state after intravenous administration is about 17 liters, indicating that valsartan is distributed in tissues not intensively. Valsartan to a large extent (94-97%) binds to blood serum proteins, mainly with albumin.

Metabolism

Valsartan is not significantly metabolized. Only about 20% dose is found in the form of metabolites. In the blood plasma, a pharmacologically inactive hydroxymetabolite is found.

Excretion

In comparison with the hepatic blood flow (about 30 l / h) the plasma clearance of valsartan occurs relatively slowly (about 2 l / h). Half-life (T_1/2) is about 9 hours.The amount of valsartan emitted through the intestine is 70% (of the amount taken internally in the dose). The kidneys excreted about 30%, mostly unchanged.

Pharmacokinetics in special patient groups

Elderly patients

In some elderly patients, the systemic effect of valsartan was somewhat more pronounced than in young patients, but it was not shown to have any clinical significance.

Patients with impaired renal function

There was no correlation between renal function and systemic valsartan. In patients with impaired renal function (creatinine clearance more than 10 ml / min), dose adjustment is not required. The experience of safe use of the drug in patients with creatinine clearance less than 10 ml / min and those on hemodialysis is absent. but valsartan has a high degree of binding to blood plasma proteins, so its elimination in hemodialysis is unlikely.

Patients with impaired hepatic function

About 70% of the absorbed dose of valsartan is excreted through the intestine, mostly unchanged. Valsartan does not undergo significant biotransformation, the systemic action of valsartan does not correlate with the degree of impaired hepatic function. Therefore, patients with hepatic insufficiency of non-biliary origin and in the absence of cholestasis do not require a dose adjustment of valsartan. The use of valsartan in patients with severe impairment of liver function has not been studied.

Patients with chronic heart failure

The average time to reach maximum concentration and the half-life of valsartan in patients with CHF are similar to those in healthy volunteers. The maximum concentration in the blood plasma (C_mOh) and the area under the curve "concentration-time" (AUC) increase linearly and practically proportionally with increasing dose in the interval of clinical doses (from 40 to 160 mg twice a day).

Indications:

- Arterial hypertension;

- chronic heart failure (II-IV functional class by classification NYHA) in patients receiving standard therapy, including diuretics, cardiac glycosides, as well as angiotensin-converting enzyme (ACE) inhibitors or beta-blockers (not simultaneously).The use of each of these drugs is not mandatory;

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

Contraindications:

- Hypersensitivity to the components of the drug;

- severe violations of liver function, biliary cirrhosis and cholestasis;

- age to 18 years;

- pregnancy, lactation;

- lactose intolerance, lactase deficiency or syndrome, glucose-galactose malabsorption.

Carefully:

With bilateral stenosis of the renal arteries; stenosis of the artery of a single kidney; 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 and vomiting); in patients with severe renal insufficiency (creatinine clearance less than 10 ml / min), including hemodialysis, when used in patients after kidney transplantation; with primary hyperaldosteronism; light and moderate violations of the liver function of non-biliary originwithout the phenomena of cholestasis; with mitral and aortic stenoses; with hypertrophic obstructive cardiomyopathy.

Pregnancy and lactation:

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 Zentiva, like any other drug that directly affects RAAS, should not be used during pregnancy. If pregnancy is detected during treatment with Valsartan Zentiva, the drug should be discontinued as soon as possible.

Data on the isolation of valsartan with breast milk are absent. Therefore, do not prescribe the drug during breastfeeding.

Dosing and Administration:

Inside, not liquid, regardless of food intake.

Arterial hypertension

The recommended initial dose is 80 mg once a day, regardless of the race, sex and age of the patient. The onset of antihypertensive action is observed within 2 hours, the maximum decrease in blood pressure is achieved within 4-6 hours. The antihypertensive effect persists for more than 24 hours. The maximum daily dose is 320 mg. It is possible to combine with diuretics.

Chronic heart failure

For 40 mg (1/2 tablets of 80 mg) 2 times a day, with a gradual increase to 80 mg 2 times a day, with good tolerability - up to 160 mg 2 times a day. The maximum daily dose is 320 mg in 2 divided doses.

The period after the transferred myocardial infarction

Treatment is started within 12 hours after myocardial infarction with an initial dose of 20 mg twice a day, followed by an increase in the dose (40 mg, 80 mg, 160 mg twice daily) for several weeks, until the target dose of 160 mg 2 times a day. Reaching a dose of 80 mg 2 times a day is recommended by the end of the second week, 160 mg twice a day - by the end of the third month of therapy. The maximum daily dose is 320 mg in 2 divided doses. Achieving the target dose depends on the tolerability of the drug during the titration period.

Elderly patients

Dose adjustments in elderly patients are not required.

Impaired liver and kidney function

In patients with impaired renal function with creatinine clearance greater than 10 ml / min, dose adjustment is not required. In patients with mild and moderate impairment of liver function without development of cholestasis, the maximum daily dose of the drug should not exceed 80 mg.

Side effects:

Frequency of side effects: very often (> 10%); often (> 1% and <10%); infrequently (> 0.1% and <1%); rarely (> 0.01% and <0.1%); very rarely (<0.01%), including individual reports; frequency - can not be set.

Patients with hypertension

From the cardiovascular system: unspecified frequency - vasculitis.

From the respiratory system: infrequently - cough.

From the digestive system: infrequently - pain in the abdomen.

From the skin: very rarely - angioedema, skin rash, itching.

From the musculoskeletal system: Unspecified frequency - myalgia.

From the urinary system: unspecified frequency - impaired renal function, increased serum creatinine concentration.

On the part of the organs of hematopoiesis: Unspecified frequency - decreased hemoglobin and hematocrit, neutropenia, thrombocytopenia.

Allergic reactions: unspecified frequency - the reaction of hypersensitivity, serum sickness.

From the sense organs: infrequently - vertigo.

Other: infrequently - increased fatigue.

Laboratory indicators: unspecified frequency - abnormal liver function, hyperbilirubinemia, increased activity of "liver" transaminases; increase of potassium concentration in blood serum.

Patients after a previous myocardial infarction and / or CHF

From the cardiovascular system: often - orthostatic hypotension and pronounced decrease in blood pressure (BP); infrequently - increased symptoms of CHF; unspecified frequency - vasculitis.

From the respiratory system: infrequently - cough.

From the digestive system: infrequently diarrhea, nausea.

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

From the sense organs: infrequently - vertigo.

From the hematopoiesis: Unspecified frequency - thrombocytopenia.

Allergic reactions: unspecified frequency - the reaction of hypersensitivity, serum sickness.

From the side of the musculoskeletal system: rarely - rhabdomyolysis; Unspecified frequency - myalgia.

From the skin: very rarely - angioedema; unspecified frequency - skin rash, itching.

From the side of the urinary tract: often - renal dysfunction; infrequently acute renal failure.

From the side of metabolism: infrequently hyperkalemia.

Other: infrequently - increased fatigue, asthenia.

Laboratory indicators: unspecified frequency - a violation of liver function, hypercreatininaemia, an increase in the concentration of urea nitrogen in the blood serum.

Overdose:

Symptoms: a marked decrease in blood pressure, which can lead to loss of consciousness and to collapse and / or shock.

Treatment: washing the stomach, taking a sufficient amount of activated charcoal, intravenous injection of 0.9% sodium chloride solution.

Valsartan is not excreted during dialysis due to active binding to plasma proteins.

Interaction:

With simultaneous use of lithium preparations with ACE inhibitors, a reversible increase in lithium content in plasma and the development of toxic effects were reported.Because of the lack of experience in the simultaneous use of valsartan and lithium, this combination is not recommended. If necessary, this combination is recommended to control the lithium content in the blood plasma.

Potassium-sparing diuretics, potassium preparations, salts containing potassium, drugs that increase the potassium content in the blood plasma (such as heparin) increase the development of hyperkalemia. If it is necessary to use together with valsartan, it is recommended to monitor the potassium content in the blood plasma.

The antihypertensive effect of the drug may be weakened when combined with non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2 (COX-2).

When treating arterial hypertension with valsartan, there were no clinically significant interactions with other concomitant medications (for example, cimetidine, warfarin, digoxin, atenolol, amlodipine, glibenclamide, furosemide, indomethacin, hydrochlorothiazide).

Other antihypertensives and diuretics increase the antihypertensive effect.

Special instructions:

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

In patients with severe sodium deficiency and / or reduced bcc, for example, receiving high doses of diuretics, in rare cases after the initiation of therapy with Valsartan Zentiva, severe arterial hypotension may occur. Before the start of treatment, it is necessary to adjust the sodium and / or BCC deficiency, for example, by lowering the dose of the diuretic.

Stenosis of the renal artery

The use of short course valsartan in twelve patients with reninvascular hypertension, which developed secondary due to unilateral stenosis of the renal artery, did not lead to 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 renal artery stenosis, it is recommended to monitor these indicators as a precautionary measure.

Chronic heart failure / period after myocardial infarction

In patients with CHF or after myocardial infarction, starting treatment with valsartan, there is often a slight decrease in blood pressure, and therefore it is recommended to monitor BP at the beginning of therapy.If you follow the recommendations on the dosing regimen, you usually do not need to cancel the drug because of hypotension.

Due to inhibition of RAAS in sensitive patients, changes in kidney function are possible. In patients with severe CHF, treatment with ACE inhibitors and angiotensin receptor antagonists may be accompanied by oliguria and / or augmentation of azotemia and, in some cases, acute renal failure and / or fatal outcome. Therefore, it is necessary to assess the extent of renal dysfunction in patients with heart failure and patients who underwent acute myocardial infarction.

Impaired renal function

The experience of safe use in patients with creatinine clearance less than 10 ml / min and in patients on hemodialysis is absent, therefore, it is necessary to use Valsartan Zentiva with caution in such patients. In patients with creatinine clearance greater than 10 ml / min, dose adjustment is not required.

During treatment with valsartan, the kidney function and the potassium content in the blood plasma must be carefully monitored.

Liver failure

In patients with mild or moderate hepatic insufficiency without the phenomena of cholestasis, Valsartan Zentiva should be used with caution.

Combination Therapy

With CHF valsartan can be prescribed both in monotherapy and in conjunction with other agents - diuretics, cardiac glycosides, as well as ACE inhibitors or beta-blockers. In patients with CHF, caution should be exercised when using a combination of an ACE inhibitor, a beta adrenoblocker and a valsartan.

With arterial hypertension, Valsartan Zentiva can be administered both in monotherapy and in conjunction with other antihypertensive agents, in particular diuretics. It is possible to use valsartan in combination with other drugs prescribed after a myocardial infarction: thrombolytics, acetylsalicylic acid as antiplatelet agents, beta-blockers and inhibitors of HMG-CoA reductase (statins).

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

Patients taking Valsartan Zentiva should be careful when driving vehicles and occupations requiring increased concentration of attention and speed of psychomotor reactions (during therapy, dizziness and fainting may occur).

Form release / dosage:

Tablets, film-coated, 80 mg, 160 mg.

Packaging:

For 14 or 15 tablets in a blister of PVC / PE / PVDC / Al.

For 2 or 6 blisters together with instructions for use in a cardboard bundle.

Storage conditions:

At a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-001726

Date of registration:02.07.2012 / 23.03.2015

Expiration Date:02.07.2017

The owner of the registration certificate:Zentiva c.s.Zentiva c.s. Czech Republic

Manufacturer: & nbsp

ZENTIVA, k.s. Czech Republic

Representation: & nbspZENTIVA PHARMA, LLCZENTIVA PHARMA, LLC

Information update date: & nbsp20.01.2017

Illustrated instructions

Instructions

Valsartan Zentiva (Valsartan Zentiva)