Теветен®

General characteristics. Structure:

Active agent: an eprosartana мезилат — 735,8 mg that corresponds to 600 mg of an eprosartan.

Excipients: cellulose of microcrystallic 43,3 mg, lactoses monohydrate of 43,3 mg, starch of prezhelatinizirovanny 43,3 mg, кросповидон 38,5 mg, magnesium stearate of 7,2 mg, the water purified 50,9 mg.

Cover: Опадрай® white (OY-S-9603) of 38,5 mg, (gipromelloza of 23,0 mg, macrogoal of 3,08 mg, mg polysorbate 80 0,39, dye: titanium dioxide (E171) of 12,03 mg).

Description

Tablets, film coated white color of an oval form biconvex with an engraving "5046" on one party. On cross section of a tablet of white color.

Pharmacological properties:

Pharmacodynamics. The antagonist of a retseptorovangiotenzin of II, selectively affects the angiotenzinovy receptors located in vessels, heart, kidneys and bark of adrenal glands forms with them strong communication with the subsequent slow dissociation. Angiotensin II contacts AT1-receptors in many fabrics (for example, in smooth muscles of vessels, adrenal glands, kidneys, heart) and causes vasoconstriction, a delay of ions of sodium and release of Aldosteronum, damage of target organs — a hypertrophy of a myocardium and vessels.

Eprosartan prevents development or weakens effects of angiotensin II, activity the system renin-angiotensin-aldosteronovoy (SRAA) oppresses. Renders vazodilatiruyushchy, hypotensive and indirectly — diuretic action.

Reduces arterial vasoconstriction, the general peripheric vascular resistance (GPVR), pressure in a small circle of blood circulation, a reabsorption of liquid and ions of sodium in a proximal segment of renal tubules, secretion of Aldosteronum. At prolonged use suppresses proliferative influence of angiotensin II on cells of unstriated muscles of vessels and a myocardium.

Hypotensive action after reception of a single dose remains within 24 hours, the lasting therapeutic effect is shown at regular reception — in 2-3 weeks without change of the heart rate (HR).

Does not cause development of orthostatic hypotension in response to reception of the first dose of drug.

At patients with arterial hypertension эпросартан does not influence concentration of triglycerides, the general cholesterol or cholesterol as a part of the lipoproteids of the low density (LPNP) in blood defined on an empty stomach. Besides, эпросартан does not influence concentration of glucose in blood on an empty stomach.

Raises a renal blood stream and a glomerular filtration rate, reduces removal of albumine (nefroprotektorny action), at preservation of renal self-control regardless of degree of manifestation of a renal failure.

Does not influence purine exchange, does not exert significant impact on removal of uric acid kidneys.

Less than inhibitors of an angiotensin-converting enzyme (APF), emergence of the effects connected with bradikinin causes (including dry persistent cough).

Frequency of cases of dry, persistent cough at the patients receiving эпросартан — 1,5%. When replacing APF inhibitor eprosartany at patients with cough, the frequency of dry persistent cough corresponds to placebo.

The treatment termination eprosartany is not followed by a syndrome of "cancellation".

During clinical trials use of drug in a daily dose to 1200 mg within 8 weeks was effective without visible dependence between a dose and frequency of the registered by-effects.

Eprosartan does not oppress isoenzymes of CYP1A, 2A6, 2S9/8, 2S19, 2D6, 2E and ZA of system of in vitro P450 cytochrome.

Pharmacokinetics. After intake of a single dose of 300 mg bioavailability makes about 13%. Communication with proteins of a blood plasma — high (98%) also remains therapeutic concentration, constant after achievement, in a blood plasma. Extent of linkng with proteins of a blood plasma does not depend on a sex, age, function of a liver and does not change at slightly expressed or moderate degree of a renal failure, but can decrease at a heavy renal failure. The maximum concentration of drug is defined by 1-2 h after intake. Meal reduces absorption by 25% (clinically not significantly), and also the maximum concentration (Cmax) and the area under a curve "concentration/time" (AUC). Distribution volume — 13 l, the general clearance −130 ml/min.

Elimination half-life (T1/2) — 5-9 h.

It is removed generally in not changed look — through intestines of 90%, kidneys — 7%. An insignificant part (less than 2%) is removed by kidneys in the form of glucuronides. 20% of concentration in urine are made by an acylglucuronide of an eprosartan, 80% — not changed drug. Practically does not kumulirut. Body weight, sexual and race do not exert impact on pharmacokinetics of an eprosartan. At patients more young than 18 years the pharmacokinetics was not studied.

Increase in advanced age of Cmax and AUC value, on average, twice that, however, does not demand correction of the mode of dosing.

At a liver failure AUC value (but not Cmax) increases, on average, for 40% that does not demand correction of the mode of dosing.

At treatment eprosartany than patients with moderate degree of the chronic renal failure (CRF) (the clearance of creatinine (CC) from 30 to 59 ml/min.) of AUC and Cmax for 30%, and with heavy degree (KK from 5 to 29 ml/min.) — is 50% higher in comparison with healthy volunteers.

Indications to use:

Arterial hypertension.

Route of administration and doses:

Inside, irrespective of meal. The recommended daily dose makes 1 tablet of the drug Teveten® once a day.

Eprosartan it is possible to apply as separately, and in a combination with other anti-hypertensive drugs. The maximum lowering of arterial pressure (ABP) at most of patients is reached in 2-3 weeks of treatment. Dose adjustment is not required for patients of advanced age and patients with a renal failure of easy and moderate severity clearance of creatinine ≥ 30 ml/min.).

For patients with a moderate and heavy renal failure (KK less than 60 ml/min.) the daily dose should not exceed 600 mg.

Features of use:

Symptomatic arterial hypotension

With reduced OTsK (as a result of therapy by diuretics), at restriction of consumption of table salt, at long and repeated vomiting administration of drug of Teveten® can cause development of symptomatic arterial hypotension in patients. Before an initiation of treatment the drug Teveten® it is necessary to carry out correction of OTsK.

Renal failure, heavy chronic heart failure

At patients whose renal function depends on activity of RAAS (for example, at heavy chronic heart failure of the IV functional class on NYHA classification) during treatment by APF inhibitors the oliguria and/or the progressing azotemia, and, in rare instances, a heavy renal failure can develop.

Due to the insufficient experience of use of antagonists of receptors of angiotensin II for patients with heavy chronic heart failure or a renal artery stenosis of the only kidney, it is impossible to exclude disturbances of renal function against the background of drug Teveten® use, owing to suppression of RAAS.

Before purpose of the drug Teveten® patients with a renal failure and, periodically, in the course of a course of therapy should control function of kidneys. If during this period deterioration in renal function is observed, it is necessary to reconsider expediency of continuation of treatment by the drug Teveten®.

Antagonists of angiotensin reduce pressure less effectively at the patients of negroid race having arterial hypertension because of higher prevalence of the states which are characterized by the low level of a renin.

Influence on ability of driving of motor transport or control of the mechanisms requiring special attention

Influence of an eprosartan on ability to driving and work with mechanisms was not studied, but on the basis of pharmakodinamichesky properties, it is possible to say that it does not exert similar impacts.

During treatment by the drug Teveten® it is necessary to be careful during the driving of motor transport and occupation potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions in connection with possibility of dizziness and weakness.

Side effects:

Most often at the patients receiving эпросартан it was reported about such side reactions on drug as a headache and not specific complaints to a state from the alimentary system, arising approximately at 11% and 8% of patients, respectively.

Frequency of the side reactions given below was defined according to the following: very often (≥1/10); often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); seldom (> 1/10000, <1/1000); very seldom (<1/10000), including separate messages.

From the central nervous system: very often — a headache, it is frequent — dizziness, an adynamy.

From cardiovascular system: infrequently — the expressed decrease in the ABP.

From respiratory system, bodies of a thorax and a mediastinum: rhinitis

From integuments and a hypodermic fatty tissue: often — allergic skin reactions (for example, skin rash, an itch), infrequently — a Quincke's disease (including persons, lips, language, a throat).

From the alimentary system: often — nonspecific complaints from digestive tract (for example, nausea, diarrhea, vomiting).

From immune system: infrequently — hypersensitivity.

From urinogenital system: the renal failure, including an acute renal failure, especially at patients is risk groups (for example, with a renal artery stenosis).

Interaction with other medicines:

Eprosartan does not influence pharmacokinetics of digoxin and a pharmacodynamics of warfarin or Glibenclamidum.

Ranitidine, кетоконазол, флуконазол do not influence pharmacokinetics of an eprosartan.

Eprosartan it is possible to apply in combination with thiazide diuretics (including with Hydrochlorthiazidum) and blockers of "slow" calcium channels, including nifedipine of the prolonged action, without expecting clinically significant undesirable interactions, at the same time there is mutual strengthening of hypotensive effect.

The combined use of Tevetena® about potassium the saving diuretics, nutritional supplements containing potassium, the substitutes of table salt containing potassium and other drugs increasing potassium level in blood serum (for example, heparin) can cause increase in level of potassium in blood serum. During treatment by the drugs influencing a renin-angeotenzin-aldosteronovuyu system development of a hyperpotassemia, especially, at patients with a renal and/or liver failure is possible.

Anti-hypertensive action of Tevetena® can be potentiated by other anti-hypertensive drugs. Cases of reversible increase in concentration of lithium in blood serum and development of toxic reactions are known at a concomitant use of drugs of lithium with APF inhibitors. It is impossible to exclude a possibility of development of similar effect after reception of an eprosartan, in this regard control of concentration of lithium in a blood plasma at a concomitant use is recommended with eprosartany.

Combined use with NPVS can result in the increased risk of deterioration in function of kidneys, including a possibility of development of an acute renal failure, and to increase in level of potassium in blood serum, especially at patients with already available renal failure. Such combinations should be applied with care, especially at elderly patients. It is recommended to patients to carry out objemzamestitelny therapy and to control function of kidneys.

Contraindications:

Hypersensitivity to drug components; pregnancy; lactation period; age up to 18 years (efficiency and safety are not established); hemodynamically significant bilateral stenosis of renal arteries and stenosis of an artery of the only kidney.

Lactose intolerance, deficit of lactase or syndrome of glyukozo-galaktozny malabsorption (drug contains lactoses monohydrate).

With care

Heavy chronic heart failure (the IV functional class on NYHA classification); decrease in the volume of the circulating blood (VCB) and/or excess removal of sodium chloride from an organism (including as a result of vomiting, diarrhea, reception of high doses of diuretics); at the patients who are on a hemodialysis or with KK less than 30 ml/min., a stenosis of aortal and mitral valves and also at a hypertrophic cardiomyopathy.

The company has no data on safety of use of the drug Teveten® for patients with an end-stage of a renal failure and recently executed transplantation of kidneys.

Теветен® it is not recommended to apply to treatment of patients with primary hyper aldosteronism.

It is necessary to observe extra care at purpose of Tevetena® for treatment of patients with an abnormal liver function and coronary heart disease, in connection with insufficient experience of use for these categories of patients.

Use at pregnancy and in the period of a lactation

The drug Teveten® is contraindicated to use during pregnancy.

The patients planning pregnancy have to pass to reception of the alternative anti-hypertensive means possessing the established characteristics of safety for use at pregnancy. Therapy by the drug Teveten® has to be stopped immediately after pregnancy establishment, and alternative therapy has to be in case of need begun.

It is known that therapy by antagonists of receptors of angiotensin II in the second and third trimesters of pregnancy is toxic for a fruit (deterioration in function of kidneys, an oligoamnios, a delay of ossification of bones of a skull) and the newborn (a renal failure, arterial hypotension, a hyperpotassemia). If nevertheless эпросартан it was applied during the period from the second trimester of pregnancy, it is recommended to carry out ultrasonic control of function of kidneys and a condition of a skull of a fruit.

Newborns whose mothers accepted эпросартан have to be observed carefully regarding detection of arterial hypotension.

Lactation period: because of the insufficient number of data on use of Tevetena® during feeding by a breast, whenever possible this drug should be replaced with other anti-hypertensive medicines possessing the established safety profiles, especially when feeding the newborn or premature child.

Overdose:

There are only limited data on overdose. Drug is well transferred at intake.

Symptoms: the expressed decrease in the ABP.

Treatment: symptomatic therapy.

Storage conditions:

In the place, dry, unavailable to children, at a temperature not above 25 °C. Period of validity 3 years. Not to apply after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 600 mg.

On 14 tablets in PVC / / the blister Is scarlet Aklar (PVDH).

On 1, 2, 4 blisters together with the application instruction in a cardboard pack.