Теветен® Plus

General characteristics. Structure:

Active agents: an eprosartana мезилат 735,8 mg (there correspond 600 mg of an eprosartan); hydrochlorothiazide of 12,5 mg

Excipients: MKTs — 43,3 mg; lactoses monohydrate — 43,3 mg; starch corn gelated — 43,3 mg; кросповидон — 38,5 mg; magnesium stearate — 7,2 mg; the water purified — 50,9 mg  

Cover: Opadry (OY3736) — 31 mg (a gipromelloza, a macrogoal 400, dyes: titanium E171 dioxide, ferrous oxide black E172, ferrous oxide yellow E172).

Pharmacological properties:

Pharmacodynamics. Eprosartan. Selectively affects the AT1 receptors located in vessels, heart, kidneys and bark of adrenal glands forms with them strong communication with the subsequent slow dissociation. Prevents development or weakens effects of angiotensin II, activity a system renin-angiotenzinovoy oppresses. Reduces arterial vasoconstriction, OPSS, pressure in a small circle of blood circulation, a reabsorption of water and sodium in a proximal segment of renal tubules, secretion of Aldosteronum. Renders the vazodilatiruyushchy, hypotensive and mediated diuretic action. At prolonged use suppresses proliferative influence of angiotensin II on cells of unstriated muscles of vessels and a myocardium. The permanent anti-hypertensive effect remains during 24 h without development of orthostatic arterial hypotension and reflex tachycardia in response to the first dose. Has nefroprotektivny effect, reducing removal of albumine, at preservation of a renal autoregulyation, regardless of degree of a renal failure. Does not exert impact on lipidic, carbohydrate and purine metabolism. At the termination of treatment does not cause a syndrome of "cancellation". Eprosartan does not strengthen such effects connected with bradikinin, and mediated by APF as, for example, cough.

Hydrochlorothiazide. The hydrochlorothiazide is thiazide diuretic. Tiazida influence mechanisms of a reabsorption of electrolytes in renal tubules, increasing removal of liquid, ions of sodium and chlorine. Thanks to diuretic action of a hydrochlorothiazide plasma volume decreases, activity of a renin in a blood plasma increases, secretion of Aldosteronum amplifies that causes increase in losses of potassium and bicarbonates with urine and decrease in potassium concentration in blood serum. The mechanism of hypotensive action of a hydrochlorothiazide — combined diuretic and vascular effects.

Теветен® Plus. At patients with raised the GARDEN эпросартан provides its statistically significant decrease. Addition to a single daily dose (600 mg) of an eprosartan of 12,5 mg of a hydrochlorothiazide provided additional statistically significant decrease the GARDEN in comparison with daily reception only of an eprosartan. The combined introduction of an eprosartan with a hydrochlorothiazide reduces the potassium loss connected with diuretic effect. The beginning of a diuresis takes place during the first 2 h, and peak effect — in 4 h. The maximum hypotensive effect develops, as a rule, in 2–3 weeks of treatment.

Pharmacokinetics. Eprosartan. After intake bioavailability — about 13%. Linkng with proteins of a blood plasma — high (98%) also remains to constants in all therapeutic range of concentration. 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 a slight or moderate renal failure, but decreases at a heavy renal failure. Cmax of drug is defined by 1–2 h after intake. At reception of an eprosartan along with food clinically insignificant decrease in absorption (less than 25%), Cmax and AUC is observed. Distribution volume — 13 l, the general Cl — 130 ml/min. At intake it is removed generally in not changed look: with a stake — 90%, with urine — 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. The body weight, sexual and racial distinctions do not exert impact on pharmacokinetics of an eprosartan. At persons under 18 the pharmacokinetics was not studied. At treatment eprosartany at patients with moderate degree of a chronic renal failure — Cl of creatinine from 30 to 59 ml/min., AUC and Cmax for 30%, and with heavy degree (Cl of creatinine from 5 to 29 ml/min.) is 50% higher in comparison with healthy people. At a liver failure AUC value (but not Cmax) increases, on average, almost for 40%. Correction of the mode of dosing at a liver failure, and also at advanced age is not required.

Hydrochlorothiazide. The hydrochlorothiazide eliminirutsya quickly by kidneys. Not less than 61% of a peroral dose eliminirutsya in not changed look during 24 h. The hydrochlorothiazide passes through a placental barrier, is allocated with breast milk.

Теветен® Plus. Simultaneous introduction of a hydrochlorothiazide and eprosartan from the clinical point of view does not make any significant impact on pharmacokinetics of both components. Meal does not influence bioavailability of an eprosartan and hydrochlorothiazide, but detains them absorption. Tmax of an eprosartan in plasma makes 4 h after reception, Tmax of a hydrochlorothiazide is 3 h.

Indications to use:

Arterial hypertension.

Route of administration and doses:

Inside, according to 1 tab. a day, in the morning, irrespective of meal.

Selection of a dose of the drug Teveten® Plus at elderly patients, patients with easy and moderate abnormal liver functions, and also patients with a renal failure (creatinine Cl more than 30 ml/min.) is not required.

Features of use:

Proceeding from pharmakodinamichesky properties, Teveten® Plus should not exert impacts on ability to driving and use of cars and mechanisms. During treatment of hypertensia 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 because there can be dizziness and weakness.

Patients with renal failures. At treatment of patients the tone of vessels and which function of kidneys preferential depend on activity system renin-angiotensin-aldosteronovoy, for example at patients with heavy heart failure of III-IV on NYHA, at a bilateral renal artery stenosis or a stenosis of an artery of the only kidney needs to be provided careful observation of function of kidneys. If during a course of treatment deterioration in renal function is observed, treatment should be reconsidered. At patients with a renal failure the azotemia connected using a hydrochlorothiazide can take place.

Patients with abnormal liver functions. The hydrochlorothiazide should be applied with care at patients with moderate or heavy forms of an abnormal liver function. There is no clinical experience of use of the drug Teveten® Plus for patients with severe damage of a liver yet.

Metabolic and endocrine effects. The hydrochlorothiazide can reduce tolerance to glucose that can demand dose adjustment of hypoglycemic means from patients with a diabetes mellitus. During a course of treatment of Tevetenom® Plus can be shown a latent diabetes mellitus. At the dose of a hydrochlorothiazide of 12,5 mg which is available in Tevetene® Plus only insignificant metabolic or endocrine effects were observed so far.

Electrolytic imbalance. The hydrochlorothiazide can lead to a hypopotassemia, a hyponatremia, a hypercalcemia, a hypomagnesiemia and a gipokhloremichesky alkalosis. For all patients who are receiving medical treatment for diuretics it is necessary to provide periodic definition of electrolytes of serum. Kaliysberegayushchy diuretics, drugs of potassium it is necessary to appoint together with Tevetenom® Plus with care.

Symptomatic hypotension. At decrease in OTsK, dehydration or decrease in content of electrolytes (for example during treatment by high doses of diuretics, repeated vomiting, long diarrhea, an electrolyte-deficient and hyposalt diet), administration of drug can cause sharp decrease in the ABP (symptomatic hypotension). Before purpose of Tevetena® Plus such disturbances should be eliminated with correction of concentration of sodium in blood and deficit of OTsK. Tranzitorny decrease in the ABP is not the reason of drug withdrawal since in this case the ABP is stabilized at further reception.

Side effects:

The general frequency of the side effects registered at the patients accepting эпросартан is comparable with that at placebo reception. These actions, as a rule, were poorly expressed and short so the termination of reception was required only from 4,1% of the patients who were receiving medical treatment eprosartany during placebo - controlled clinical trials (6,5% — at group placebo).
From TsNS: seldom — a headache, dizziness, weakness.
From skin: seldom — the fast-passing rash, a skin itch, a small tortoiseshell.
From cardiovascular system: very seldom — decrease in the ABP, a Quincke's disease.

The hydrochlorothiazide did not increase the frequency of emergence of by-effects. For long-term experience of use of a hydrochlorothiazide in clinical practice the following side effects were recorded:
from a GIT: anorexia, nausea, vomiting, diarrhea, lock, jaundice, pancreatitis;
from a nervous system: dizziness, weakness, paresthesia, adynamy, headache, concern;
from cardiovascular system: hypotension, orthostatic hypotension;
from the hemopoietic and lymphatic systems: leukopenia, agranulocytosis, thrombocytopenia, aplastic and hemolitic anemias;
from kidneys: intersticial nephrite, renal failure;
from lungs: pneumonitis, fluid lungs;
from skin: the fast-passing rash, a vasculitis, a toxic and epidermal necrolysis, a system lupus erythematosus;

metabolism: hyperglycemia, hyperuricemia, gout, hyponatremia, hypopotassemia, hypochloraemia, hypercalcemia, hypomagnesiemia, hypercholesterolemia, gipertriglitseridemiya;
others: spasms, disturbance of sexual function, fever, anaphylactic reactions.

Interaction with other medicines:

The hypotensive effect can amplify at parallel use with other antihypertensives. At use together with peroral hypoglycemic means it is necessary to carry out correction of their dose since the hydrochlorothiazide can reduce tolerance to glucose. Perhaps reversible increase in concentration of lithium in plasma and increase in risk of emergence of its toxic effects (careful monitoring of concentration of lithium at the patients who are at the same time accepting Teveten® Plus and lithium is necessary). NPVS can reduce diuretic and hypotensive effect of Tevetena® Plus. Reducing potassium level, the hydrochlorothiazide can strengthen effect of cardiac glycosides and some antiarrhytmic HP. The hydrochlorothiazide increases risk of emergence of a hypopotassemia at its appointment together with the drugs causing loss by a potassium organism, for example with the diuretics having potassiumuretic effect, laxatives, glyukokortikortikoida and adrenocorticotropic hormone (AKTG). The hydrochlorothiazide can strengthen action of not depolarizing muscle relaxants (for example tubocurarine). Absorption of a hydrochlorothiazide decreases at joint reception of the anion-exchange pitches, for example Colestyraminum or a kolestipol.

Contraindications:

- hypersensitivity to any of components of drug and to streptocides;
- pregnancy;
- breastfeeding period;
- renal failure (creatinine Cl <30 ml/min.);
- age up to 18 years (efficiency and safety are not established).

With care:
- heavy heart failure of III-IV (on NYHA);
- bilateral stenosis of renal arteries, renal artery stenosis of the only kidney;
- decrease in OTsK, dehydration, loss of electrolytes, treatment by high doses of diuretics, repeated vomiting, long diarrhea, electrolyte-deficient diet;
- the moderated or expressed abnormal liver function;
- diabetes mellitus.

Use at pregnancy and feeding by a breast
Contraindicated at pregnancy. For the period of treatment it is necessary to stop breastfeeding.

Overdose:

There are no data on overdose now.

Symptoms: possible — excessive decrease in the ABP, dehydration and an electrolytic imbalance (a hypopotassemia, a hypochloraemia, a hyponatremia) which are shown in the form of nausea and drowsiness.

Treatment: depending on time which passed after meal, the taken measures have to include stimulation of vomiting, a gastric lavage and/or reception of absorbent carbon. At sharp decrease in the ABP it is recommended to lay the patient on a back, to raise legs, if necessary to enter plasma substituting liquids. At dehydration and disturbance of water-salt balance the symptomatic and maintenance therapy is recommended. The hemodialysis is inefficient.

Storage conditions:

In the dry place, at a temperature not above 25 °C.
To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

In the blister of 14 pieces; in a pack cardboard 1, 2 or 4 blisters.