Klosart

General characteristics. Structure:

Active ingredient: losartan; 1 tablet contains a lozartan of potassium of 25 mg or 50 mg.

Auxiliary veshchestva:tsellyuloza microcrystallic, sodium of a kroskarmelloz, magnesium stearate, silicon dioxide colloid anhydrous, covering of Opadray of O3B 52014 yellow.

Pharmacological properties:

Pharmacodynamics. Angiotensin II, a powerful vasoconstrictor, is active hormone a renin-angiotenzinovoy of system and one of the most important factors of a pathophysiology of hypertensia. Angiotensin II contacts a receptor of AT1 which is found in many fabrics (for example, in unstriated muscles of vessels, epinephral glands, kidneys and heart), defining a number of important biological effects, including vasoconstriction and release of Aldosteronum. Angiotensin II also stimulates proliferation of smooth muscle cells. The second receptor of AT2 angiotensin was identified as subtype of receptors of AT2, but its value in a cardiovascular homeostasis is not established. Lozartan – strong substance, synthetic, active at oral administration. It selectively contacts AT1 receptor. In conditions іп vitro and іп vivo лозартан and it pharmacological an active metabolite – carboxyl acid (E-3174) – block all physiologically powerful influences of angiotensin II, irrespective of a source or a way of synthesis. Lozartan selectively contacts AT1 receptor, does not communicate and does not block other receptors of hormones or ion channels which play an important role in regulation of cardiovascular system. Moreover, лозартан APF (a kininaza of II) – enzyme which renders assistance of disintegration of bradikinin does not oppress. Thereof the effects which are directly not connected with blockade of a receptor of AT1 such as strengthening of influences which mediator is bradykinin, or formation of hypostases are not associated using a lozartan. Use of a lozartan allows to reduce total quantity of cases of death for the cardiovascular reason, a stroke and a myocardial infarction at patients with arterial hypertension with a hypertrophy of a left ventricle, provides protection of kidneys at patients with a diabetes mellitus ІІ type with a proteinuria.

Pharmacokinetics. Absorption. After oral administration лозартан well is soaked up and exposed to metabolism of the first origin with formation of an active metabolite of carboxyl acid and inactive metabolites. System bioavailability of tablets of a lozartan makes about 33%. Average peak concentration of a lozartan and its active metabolite are reached, respectively, in 1 hour and 3–4 hours. When drug was used together with the standardized food, clinically powerful influence on a concentration profile in plasma of a lozartan was not observed.

Distribution. Lozartan and his active metabolite on ³ 99% contact plasma proteins, first of all albumine. The volume of distribution of a lozartan makes 34 l. Researches indicate what лозартан badly gets through a blood-brain barrier if at all gets through it.

Metabolism. About 14% of a dose of the lozartan accepted inside are converted into its active metabolite. After oral administration of the 14C-marked lozartan of potassium the circulating plasma radioactivity first of all is connected with lozartany and its active metabolite. Except an active metabolite, inactive metabolites, including two important metabolites created by a hydroxylation of a chain of a butyl row and also a small metabolite – M-2-tetrazolglyukuronid form.

Elimination. The Plazmovy clearance of a lozartan and its active metabolite makes respectively 600 ml/min. and 50 ml/min. The renal clearance of a lozartan and its active metabolite makes, respectively, about 74 ml/min. and 26 ml/min. When лозартан apply orally, about 4% of a dose are allocated in not changed view with urine, and about 6% of a dose are allocated with urine in the form of an active metabolite. Pharmacokinetic properties of a lozartan and its active metabolite linear at peroral doses of a lozartan of potassium to 200 mg.
After oral administration of concentration in plasma of a lozartan and its active metabolite, respectively, about 2 hours and 6–9 hours decrease polieksponentsialno with terminal time of semi-removal. After oral administration of the 14C-marked lozartan by the person, about 35% of radioactivity define in urine, and 58% – in excrements.

Indications to use:

Indications:
- Arterial hypertension.
- Arterial hypertension and a hypertrophy of a left ventricle (for the purpose of reduction of risk of complications and mortality owing to cardiovascular disturbances).
- A diabetes mellitus of the II type with a proteinuria (for delay of progressing of a disease of kidneys, and also for reduction of a proteinuria).

Route of administration and doses:

Arterial hypertension.
The usual initial and maintenance dose for most of patients makes 50 mg of drug once a day. The maximum anti-hypertensive effect is reached on 3–6 week from initiation of treatment КЛОСАРТ®ом. For some patients more favorable can be an increase in a dose of drug to 100 mg a day.
Patients with a reduced intravascular volume (for example, owing to treatment by high doses of diuretics) need to begin therapy with a dose of 25 mg of 1 times a day. At appointment КЛОСАРТ®а to elderly people or patients with disturbances of renal function, including to those which are on dialysis it is not necessary to carry out initial dose adjustment. The dose decline can be required at patients with signs of an abnormal liver function.
For reduction of risk of complications and mortality for the cardiovascular reasons at patients with arterial hypertension and a hypertrophy of a left ventricle
The usual initial dose makes 50 mg of КЛОСАРТ®á 1 times a day. Depending on changes of level of arterial pressure add a low dose of a hydrochlorothiazide and/or increase dose КЛОСАРТ®а to 100 mg of 1 times a day.

Protection of kidneys at patients with a diabetes mellitus of the II type with a proteinuria
The usual initial dose makes 50 mg of 1 times a day. It is possible to increase a dose to 100 mg once a day, depending on changes of level of arterial pressure. КЛОСАРТ® it can be appointed together with other anti-hypertensive means (for example, with diuretics, blockers of calcium channels, alpha or beta-blockers and drugs of the central action), and also with insulin and other widespread hypoglycemic means (for example, derivatives of sulphonylurea, a glitazonama and inhibitors of glucosidase).
КЛОСАРТ® it can be applied irrespective of meal.
Drug can be appointed together with other anti-hypertensive means.

Features of use:

КЛОСАРТ® it is possible to accept irrespective of food.
Patients with deficit of sodium and dehydration (owing to use of high doses of diuretics, the limited use of liquid, diarrhea, vomiting) can have a symptomatic arterial hypotension. For its prevention correction of the specified disturbances before an initiation of treatment lozartany or decrease in an initial dose of drug is recommended.
The risk of emergence of an electrolytic imbalance increases at patients with damage of kidneys, including in the presence of a diabetes mellitus which demands the corresponding medical control.
Pharmacokinetic data indicate important increase in concentration of a lozartan in plasma of patients with cirrhosis that demands dose decline КЛОСАРТ®а from patients with abnormal liver functions, including in the anamnesis.
It is necessary to be careful, appointing КЛОСАРТ® to patients with the expressed renal failures, patients with a bilateral stenosis of renal arteries, a renal artery stenosis of the only kidney, after operation of transplantation of kidneys. In the specified cases drugs which influence a renin-angiotenzinovuyu system can cause increase in levels of urea and creatinine in blood.
In the available clinical trials differences concerning efficiency and safety of use КЛОСАРТ®а depending on age were not revealed. Nevertheless, patients of advanced age can have hypersensitivity to effect of drug, even at use of usual doses.

Ability to influence speed of response at control of motor transport or work with other mechanisms.
There are no data on influence of drug on ability to direct the car and to work with a difficult technique.
Nevertheless, before definition of individual reaction on лозартан it is necessary to adhere to care at control of motor transport and occupations potentially dangerous types of activity which demand concentration of attention and speed of psychomotor reactions.

Use during pregnancy or feeding by a breast.
Prescription of medicines which exert direct impact on a renin-angiotenzinovuyu system is contraindicated during pregnancy. At once after pregnancy establishment use of a lozartan needs to be stopped immediately.
It is not known whether it is allocated лозартан in mother's milk. That a significant amount of medicines is excreted in milk, and also considering interests of mother and child, it is necessary to make the decision or on the feeding termination, or on drug withdrawal.

Children. Safety and efficiency of use of a lozartan at treatment of children are not proved therefore it is not necessary to appoint КЛОСАРТ® this age category.

Side effects:

At essential hypertensia in controlled clinical trials dizziness was the only, connected using drug, side reaction which arose with bigger, than for placebo, frequency at ≥ 1% of patients who were treated КЛОСАРТ®ом. Besides, dozozavisimy orthostatic effects were observed less than at 1% of patients. It was occasionally reported about rashes though their frequency was smaller, than for group of placebo. Dizziness, adynamy/fatigue were the most frequent side effects connected using drug at patients with arterial hypertension and a hypertrophy of a left ventricle in controlled clinical trial.
The adynamy/fatigue, dizziness, hypotension and hyperpotassemia were the most widespread side effects at patients with a diabetes mellitus of the II type and a proteinuria in controlled clinical trial connected using drug.
- Organism generally: abdominal pain, adynamy/fatigue, thorax pain, hypostases/puffiness.
- Cardiovascular system: heart consciousness, tachycardia.
- Digestive tract: diarrhea, dyspepsia, nausea.
- Liver: in isolated cases – hepatitis; aberrations of indicators of function of a liver.
- Musculoskeletal system: dorsodynia, muscular spasms, mialgiya.
- Central nervous system: discomfort, headache, sleeplessness.
- Respiratory system: cough, cold, pharyngitis, sinusitis, upper respiratory tract infection.
- Blood: anemia.
- Allergic reactions: seldom – a Quincke's disease, including hypostasis of a throat and uvula which leads to obstruction of respiratory tracts and/or a face edema, lips, a throat and/or language; urticaria, itch.
- Laboratory indicators: hyperpotassemia (serum potassium> 5,5 ¼Ø¬ó/l), increase in ALT.

Interaction with other medicines:

Drug can be appointed with other anti-hypertensive means (diuretics, blockers of calcium channels, beta adrenoblockers, etc.). Still clinically powerful interactions of a lozartan with a hydrochlorothiazide, digoxin, warfarin, Cimetidinum, phenobarbital, ketokonazoly and erythromycin are not revealed.
Rifampicin and флуконазол are capable to reduce concentration of an active metabolite of a lozartan in a blood plasma. Clinical effects of these interactions were not estimated.
As well as at use of other drugs which block angiotensin II or its effects, simultaneous use of kaliysokhranyayushchy diuretics (for example, Spironolactonum, Triamterenum, amiloride) of potassium drugs or salt substitutes which contain potassium can lead to increase in contents of potassium in blood serum.
Non-steroidal anti-inflammatory drugs (NPVS), including the selection inhibitors of cyclooxygenase-2 (TsOG-2), can weaken anti-hypertensive effect of antagonists of receptors of angiotensin ІІ.
At some patients with an impaired renal function who receive treatment of NPVS including TsOG-2 inhibitors, simultaneous use of antagonists of receptors of angiotensin ІІ can lead to further deterioration in function of kidneys. These effects usually are reverse.
Co-administration of a lozartan and APF inhibitors is studied insufficiently.

Contraindications:

Hypersensitivity to a lozartan or any other component of drug. Period of pregnancy and feeding by a breast. Children's age up to 18 years.

Overdose:

The overdoses given relatively lozartany limited. The most probable manifestations of overdose are hypotension and tachycardia; bradycardia can be a consequence of parasympathetic (vagal) stimulation. If there is symptomatic hypotension, it is necessary to appoint the supporting treatment.
лозартан, its active metabolite are not removed at a hemodialysis.
At accidental overdose it is necessary to carry out a symptomatic and maintenance therapy. The recommended measures is stimulation of vomiting and a gastric lavage.

Storage conditions:

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

Issue conditions:

According to the recipe

Packaging:

On 14 tablets in the blister; on 1 or 2 blisters in cardboard packaging.