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

40 mg: Oval biconvex tablets white or almost white, film-coated,with a risk on both sides. Cross-sectional view: the outer ring of the shell, as well as the core of the tablet is white or almost white.

80 mg: Oval biconvex tablets from red to red with a pinkish tinge color, covered with a film sheath, with a risk on both sides. View of the transverse cut, outer shell ring from red to red with a pinkish hue of color, and the core of the tablet is white or almost white.

160 mg: Oval, biconvex tablets are yellow, film-coated, with a risk on both sides. Cross-sectional view: the outer ring of the shell is yellow and the core of the tablet is white or almost white.

220 mg: Oval, biconvex tablets are yellow, film-coated, with a risk on one side. Cross-sectional view: the outer ring of the shell is yellow and the core of the tablet 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:

Valsartan - a specific antagonist of angiotensin II receptors, intended for oral administration.It exerts an antagonistic action selectively on the AT subtype receptors₁, 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. Does not have any expressed agonist 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 active hormone of the renin-angiotensin-aldosterone system (RAAS) is angiotensin II, which is formed from angiotensin I with the participation of an angiotensin-converting enzyme (ACE). Angiotensin II binds to specific receptors located on cell membranes in various tissues. Has a wide range of physiological effects, including, primarily, both direct and indirect participation in the regulation of blood pressure (BP).

Being a potent vasoconstrictor, angiotensin II causes a direct pressor response. In addition, it promotes sodium retention and stimulates the secretion of aldosterone.

In the treatment of valsartan in patients with arterial hypertension, there is a decrease in blood pressure, not accompanied by a change in the heart rate (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, Depending on the dose taken, it is usually achieved in 2-4 weeks and maintained at the achieved level during prolonged therapy.

The sudden discontinuation of valsartan is not accompanied by a sharp increase in blood pressure or other undesirable clinical consequences.

Tolerance to physical activity

When assessing the effect of valsartan (prescribed additionally to the standard therapy of heart failure) on the tolerability of physical activity in patients with chronic heart failure (CHF) II-IV functional classes by classification NYHA and with a left ventricular ejection fraction (LVEF) of less than 40%, there was an increase in exercise time compared to baseline.

Pharmacokinetics:

Suction. After taking the drug, suction of valsartan takes place quickly, but the degree of absorption varies widely. The average absolute bioavailability of valsartan is 23%. The time to reach the maximum concentration (TC_m_Oh) - 2 h.

In the range of doses studied, the kinetics of valsartan is linear. With repeated use of the drug, no changes in the kinetic parameters were noted.

When taking valsartan with food, the area under the concentration-time curve decreases (AUC) by 48%. However, 8 hours after taking the drug, plasma concentrations of valsartan taken on an empty stomach and with food are 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.

Distribution. When taking the drug once a day, cumulation is negligible. Concentrations of the drug in blood plasma in women and men are the same. Valsartan to a significant extent (by 94-97%) binds to blood serum proteins, mainly with albumin. The volume of distribution during the equilibrium period is low (about 17 liters).

Metabolism. The drug is metabolized by the enzyme system CYP2C9.

Excretion. In comparison with the hepatic blood flow (about 30 l / h), the plasma clearance of valsartan occurs relatively slowly (about 2 L / h). The half-life (T_1/2) is 9 hours. It is excreted through the intestine - 70%, by the kidneys - 30%, mainly in unchanged form (20% in the form of metabolites).

Pharmacokinetics in selected patient groups

Elderly patients (over 65 years of age)

In some elderly patients, the systemic effect of valsartan was somewhat more pronounced than in young patients, however, no clinical significance of this was shown.

Patients with impaired renal function

There was no correlation between renal function and systemic exposure to valsartan, which was to be expected, given that for this substance, the kidney clearance is only 30% of the total clearance value. Therefore, in patients with impaired renal function, dose adjustment is not required. 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 amount absorbed dose of the drug is excreted with bile, mostly unchanged. Valsartan does not undergo significant biotransformation, and, as can be expected, systemic exposure to valsartan does not correlate with the degree of hepatic impairment. Therefore, patients with hepatic insufficiency of non-biliary origin and in the absence of cholestasis do not require a dose adjustment of valsartan. In patients with biliary liver cirrhosis or bile duct obstruction AUC valsartan is approximately 2-fold increased.

Indications:

- Arterial hypertension;

- chronic heart failure (II-IV functional class by classification NYHA) - as part of complex therapy on the background of standard therapy and in patients not receiving ACE inhibitors;

- reduction of cardiovascular mortality in stable patients who developed left ventricular failure / dysfunction due to myocardial infarction.

Contraindications:

- Hypersensitivity to any of the components of the drug;

- pregnancy, lactation period;

- age under 18 years (effectiveness and safety not established);

- Lactase deficiency, lactose intolerance, glucose-galactose malabsorption (the preparation contains lactose);

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

- hereditary angioedema, use in patients with angioedema has developed during previous therapy with ACE inhibitors or angiotensin receptor antagonists (APA).

Carefully:

Two-sided stenosis of the renal arteries, stenosis of the artery of a single kidney, with a diet with restriction of consumption of table salt, in conditions accompanied by a decrease in the volume of circulating blood (including diarrhea, vomiting), mild and moderate violations of the liver function of non-biliary genesis without the phenomena of cholestasis, renal failure (creatinine clearance less than 10 ml / min), including in patients on hemodialysis, mitral or aortic stenosis, hypertrophic obstructive cardiomyopathy, use in the patient in after kidney transplantation, primary aldosteronism, systemic lupus erythematosus.

Pregnancy and lactation:

The use of the drug Tantordio is not recommended during pregnancy, as well as in women,planning pregnancy. Given the mechanism of action of angiotensin II receptor antagonists, the risk to the fetus can not be ruled out. The action of ACE inhibitors (drugs that affect RAAS) on the fetus, if used in the second and third trimester of pregnancy, can lead 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 during pregnancy accidentally received valsartan. When using drugs 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 diagnosed during therapy with Tantordio, treatment should be discontinued as soon as possible.

There is no data on the isolation of valsartan in breast milk. Therefore, the question of stopping breastfeeding or abolishing therapy for Tantordio drugs should be addressed.

Dosing and Administration:

Take the tablets inside without chewing, regardless of food intake.

With arterial hypertension the recommended dose is 80 mg 1 time / day daily, regardless of the age and sex of the patient. Antihypertensive effect is observed in the first 2 weeks of treatment; The maximum effect is observed after 4 weeks. Patients who can not achieve an adequate reduction in blood pressure, a daily dose of the drug can be increased to 160 mg or additionally prescribed diuretics. The maximum daily dose is 320 mg per day (in two divided doses). Patients with renal and hepatic impairment of non-biliary origin and without cholestasis are not required to change the dose of the drug. Possible simultaneous use with diuretics.

With chronic heart failure the recommended initial dose is 40 mg 2 times a day. It is possible to gradually increase the dose 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 divided into 2 divided doses, and a dose reduction of concomitantly taken diuretics may be required.

In patients who are simultaneously receiving diuretics, as well as in patients with chronic heart failure regular monitoring of renal function, blood pressure.At the appearance of clinical signs of arterial hypotension, it is necessary to reduce the dose.

In patients with mild and moderate impairment of liver function non-biliary genesis without the phenomena of cholestasis the drug should be used with caution, the daily dose should not exceed 80 mg.

After a recent myocardial infarction: treatment is started within 12 hours after myocardial infarction in an initial dose of 20 mg twice a day, followed by an increase in the dose (40 mg, 80 mg, 160 mg twice a day) 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.

Side effects:

To assess the frequency of adverse events, the following criteria were used: very often (≥1 / 10), often (≥1 / 100, but <1/10), infrequently (≥1 / 1000, but <1/100), rarely (≥1 / 10 000, but <1/1000), very rarely (<1/10 000, including single messages).

From the central nervous system: often - headache, dizziness, including postural; infrequently - insomnia; Vertigo, fainting (when used after a heart attack), decreased libido.

From the respiratory system: often - cough, pharyngitis, rhinitis, sinusitis.

From the cardiovascular system: often - marked decrease in blood pressure and orthostatic hypotension; infrequently (when used after a heart attack, myocardial infarction) - heart failure.

From the gastrointestinal tract: infrequently - nausea, diarrhea, abdominal pain.

From the musculoskeletal system: infrequently - back pain, myalgia, arthralgia.

From the genitourinary system: very rarely - renal dysfunction, acute renal failure.

Allergic reactions: very rarely - angioedema, skin rash, itching, hypersensitivity reactions, including serum sickness and vasculitis.

From the laboratory parameters: rarely - reduction of hemoglobin and hematocrit, neutropenia, thrombocytopenia, hypercreatinemia, hyperbilirubinemia, increased activity of "hepatic" transaminases, increased serum urea nitrogen, hyperkalemia.

Other: often - viral infections, general weakness; infrequently - peripheral edema, asthenia, fatigue, upper respiratory tract infections.

Overdose:

Symptoms: despite the lack of sufficient data, the main expected manifestation of an overdose of the drug will be tachycardia and a marked decrease in blood pressure, which can lead to collapse and / or shock.

Treatment: there is no specific antidote. If the drug is taken recently, you should induce vomiting, rinse the stomach, take Activated carbon. With a marked decrease in blood pressure, the usual method of treatment is an intravenous injection of 0.9% sodium chloride solution. Hemodialysis is ineffective.

Interaction:

Clinically significant interactions with such drugs as: cimetidine, warfarin, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine and glibenclamide not found.

Because the valsartan does not undergo any significant metabolism, it is unlikely that clinically significant interactions with other drugs at the metabolic level, which are the result of induction or inhibition of the cytochrome P450 system.

Although valsartan is largely associated with blood plasma proteins, there is no significant interaction with diclofenac and furosemide.

Simultaneous use with potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride), preparations of potassium or salts containing potassium, can lead to an increase in potassium in the blood serum. If such simultaneous application is considered necessary, care must be taken.

With the simultaneous use of lithium preparations with ACE inhibitors, there have been reports of a reversible increase in lithium content in the blood plasma and an increase in its toxicity. In very rare cases, such changes were observed when taking lithium preparations with antagonists of the angiotensin II receptor. Caution is advisable to use lithium preparations with Tantordio. If this combination is necessary, then it is recommended to control the lithium content in the blood plasma.

Special instructions:

Deficiency in the body of sodium and / or reduced 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, clinically pronounced arterial hypotension may occur at the onset of treatment with Tantordio.

Before the start of treatment, a correction should be made in the body of sodium and / or the volume of circulating blood, for example, by decreasing the dose of the diuretic. In the case of development of arterial hypotension, the patient should be placed on his back, and, if necessary, an intravenous infusion of 0.9% sodium chloride solution. After the BP stabilizes, the treatment can be continued.

Stenosis of the renal artery

Given that other drugs that affect RAAS can cause an increase in serum urea and creatinine in patients with bilateral or unilateral stenosis of the renal artery, systematic monitoring of these indications is recommended as a precautionary measure.

Renal impairment

Patients with impaired renal function do not need a dose adjustment for Tantordio. However, with pronounced disorders (when creatinine clearance is less than 10 ml / min.), It is recommended that caution be exercised.

Impaired liver function

Patients with hepatic insufficiency do not need to adjust the dose of the drug. Valsartan is mainly excreted unchanged with bile, but in patients with bile duct obstruction the valsartan clearance is reduced.When prescribing Tantordio, these patients should be very careful.

Chronic heart failure

Due to oppression of RAAS in sensitive patients, changes in renal function are possible. In patients with severe chronic heart failure, treatment with ACE inhibitors and angiotensin receptor antagonists may be accompanied by oliguria and / or increased azotemia and (rarely) acute renal failure and / or fatal. Therefore, it is necessary to assess the degree of impaired renal function in patients with heart failure.

Pediatric Use

Since there have been no controlled trials of the efficacy and safety of valsartan in children and adolescents under the age of 18, it is not possible to formulate specific recommendations for use in this group of patients.

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

Studies to study the effect of the drug Tantordio on the ability to drive vehicles and use of technical means were not conducted. However, care should be taken, as dizziness or fatigue may occur during treatment.

Form release / dosage:

Tablets coated with a coating, 40 mg, 80 mg, 160 mg and 320 mg.

Packaging:

7 or 10 tablets in a blister of aluminum foil.

1, 2, 3, 4, 5, 6, 7, 8 blisters with instructions for use in a cardboard box.

Storage conditions:

Store in a dry place at a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the date shown on the package.

Terms of leave from pharmacies:On prescription

Registration number:PL-000843

Date of registration:11.10.2011

Date of cancellation:2016-10-11

The owner of the registration certificate:Torrent Pharmaceuticals Co., Ltd.Torrent Pharmaceuticals Co., Ltd. India

Manufacturer: & nbsp

TORRENT PHARMACEUTICALS, Ltd. India

Representation: & nbspTORRENT PHARMACEUTICALS LTD. TORRENT PHARMACEUTICALS LTD. India

Information update date: & nbsp07.12.2015

Illustrated instructions

Instructions

Tandordio (Tantordio)