Лориста®

General characteristics. Structure:

Kernel:
Active ingredient: lozartana potassium - 12,5 mg; 25 mg; 50 mg; 100 mg.
Excipients: tsellaktoza * (mix of lactose of monohydrate and cellulose), starch prezhelatinizirovanny, starch corn, cellulose microcrystallic, silicon dioxide colloid anhydrous, magnesium stearate.
Cover: gipromelloza, talc, propylene glycol, dye quinolinic yellow **, E104, titanium dioxide, E171.
* - a tsellaktoza - mix of lactose of monohydrate and cellulose.
** - apply at production of tablets a dosage 12,5 mg and 25 mg, do not apply to production of tablets a dosage of 50 and 100 mg.

Description
Tablets of 12,5 mg. Oval, slightly biconvex tablets, film coated from light yellow till yellow color, with a facet.
Tablets of 25 mg. Oval, slightly biconvex tablets, film coated, yellow color, with risky on one party and a facet.
Tablets of 50 mg. Round, slightly biconvex tablets, film coated, white color, with risky on one party, with a facet.
Tablets of 100 mg. Oval, slightly biconvex tablets, film coated, white color.

Pharmacological properties:

Pharmacodynamics. Lozartan is the selection antagonist of receptors of angiotensin II (AT1 type) for intake, the nonprotein nature. In vivo and in vitro lozartan and its biologically active carboxyl metabolite (EHR-3174) block all physiologically significant effects of angiotensin II on AT1 receptors irrespective of a way of its synthesis: leads to increase in activity of a renin of a blood plasma, reduces concentration of Aldosteronum in a blood plasma, etc.
lozartan indirectly causes activation of AT1-receptors due to increase in level of angiotensin II.
lozartan does not suppress activity of a kininaza of II, enzyme which participates in metabolism of bradikinin.
Reduces the general peripheric vascular resistance (GPVR), pressure in a "small" circle of blood circulation; reduces an afterload, renders diuretic effect. Interferes with development of a hypertrophy of a myocardium, increases tolerance to an exercise stress at patients with the chronic heart failure (CHF). Reception lozartana leads to statistically significant decrease in the systolic and diastolic arterial pressure (AP) once a day. lozartan evenly controls pressure for days, at the same time the anti-hypertensive effect corresponds to a natural circadian rhythm. The lowering of arterial pressure (ABP) at the end of action of a dose of drug made about 70-80% of effect for dive of effect of drug, in 5-6 hours after reception. The syndrome of "cancellation" is not observed; also lozartan does not exert clinically significant impact on the heart rate (HR).
lozartan it is effective at men and women, and also at elderly (> 65 years) and younger patients (<65 years).

Pharmacokinetics. Lozartan it is well soaked up from digestive tract. Is exposed to considerable metabolism at "the first passing" through a liver, forming an active metabolite (EHR-3174) with carboxyl acid and other inactive metabolites. Bioavailability makes about 33%. Administration of drug with food does not exert clinically significant impact on its serumal concentration. TCmax - 1 hour after intake, and its active metabolite (EHR-3174) - 3-4 hours.
More than 99% lozartana and EHR-3174 contact proteins of a blood plasma, preferential, albumine. Distribution volume lozartana is equal to 34 l. Very badly gets through a blood-brain barrier.
lozartan it is metabolized with formation of an active (EHR-3174) metabolite (14%) and inactive, including two main metabolites which are formed by a hydroxylation of butilny group of a chain and less significant metabolite, N-2-tetrazole a glucuronide.
The plasma clearance lozartana and its active metabolite is made by about 10 ml/sec. (600 ml/min.) and 0,83 ml/sec. (50 ml/min.) respectively. The renal clearance lozartana and its active metabolite is made by about 1,23 ml/sec. (74 ml/min.) and 0,43 ml/sec. (26 ml/min.). The elimination half-life lozartana and an active metabolite makes 2 hours and 6-9 hours, respectively. It is removed preferential with bile of-58%, kidneys of-35%.

Indications to use:

• Arterial hypertension.
• Decrease in risk of development of a stroke in patients with arterial hypertension and a hypertrophy of a left ventricle.
• Chronic heart failure (as a part of a combination therapy, at intolerance or inefficiency of therapy by APF inhibitors).
• Protection of function of kidneys at patients with a diabetes mellitus 2 types with a proteinuria for the purpose of decrease in a proteinuria, reduction of progressing of damage of kidneys, decrease in risk of development of an end-stage (prevention of need of carrying out dialysis, probability of increase in level of creatinine of blood serum) or approach of death.

Route of administration and doses:

To accept inside, regardless of meal, frequency rate of reception of-1 times a day.

Arterial gipertetiya: the average daily dose makes 50 mg. The maximum anti-hypertensive effect is reached within 3-6 weeks of therapy. At some patients it is possible to reach more expressed effect by increase in a dose of drug up to 100 mg a day in two steps or in one step.
Against the background of reception of high doses of diuretics it is recommended to begin therapy by Lorista with 25 mg a day in one step. At patients of advanced age, and also correction of an initial dose is not required from patients with renal failures, including patients on a hemodialysis.
It is not required to adjust a dose to patients of old age or patients with an impaired renal function, including the patients who are on a hemodialysis.
Patients with abnormal liver functions should appoint lower doses of drug.

Chronic heart failure: the initial dose makes 12,5 mg a day in one step. To reach a usual maintenance dose in 50 mg a day a dose of drug it is necessary to increase gradually, bucketed in one week (for example, 12,5 mg, 25 mg, 50 mg at a single dose in days). Lorista is usually appointed in a combination with diuretics and cardiac glycosides.

The dose of drug has to increase according to the following scheme:
1 week: from 1 to 7 day - on 1 tablet of 12,5 mg once a day.
2 week: from 8 to 14 day - on 1 tablet of 25 mg once a day.
3 week: from 15 to 21 days - on 1 tablet of 50 mg once a day.
4 week; from 22 to 28 day - on 1 tablet of 50 mg once a day.

Decrease in risk of development of a stroke in patients with arterial hypertension and a hypertrophy of a left ventricle: the standard initial dose of Lorista makes 50 mg a day in one step. Further the hydrochlorothiazide in low doses can be added and/or Lorista's dose to 100 mg a day is increased.

Protection of kidneys at patients with a diabetes mellitus 2 types with a proteinuria: the standard initial dose of Lorista makes 50 mg a day in one step. The dose of drug can be increased to 100 mg a day taking into account decrease in the ABP.

Use in pediatrics
Safety and efficiency of drug at children are not established.

Features of use:

At patients with a reduced volume of the circulating blood (for example, at therapy by high doses of diuretics) symptomatic arterial hypotension can develop. Prior to reception lozartana it is necessary to eliminate the available disturbances, or to begin therapy with small doses.
Patients with slight and moderate cirrhosis have concentration lozartana and than its active metabolite in a blood plasma after oral administration is higher, than at healthy. Therefore therapy is recommended to patients with liver diseases in the anamnesis by lower doses.
At patients with a renal failure, both with a diabetes mellitus, and without it, electrolytic disturbances (hyperpotassemia) to which it is necessary to pay attention often develop. However only in rare instances stop treatment owing to a hyperpotassemia. During treatment it is regularly necessary to control potassium concentration in blood, especially at patients of advanced age, at renal failures.
The medicines operating on a renin-angiotenzinovuyu system can increase the content of urea and creatinine in blood serum at patients with a bilateral or unilateral stenosis of an artery of the only kidney. Changes of function of kidneys can be reversible after therapy cancellation. During treatment it is regularly necessary to control concentration of creatinine in blood serum, at regular intervals.
Influence on ability to drive the car and other mechanical means: data on influence lozartana on ability to manage transport or other technical means are absent.

Side effects:

In most cases Lorista is well had, side effects have weak and passing character and do not demand drug withdrawal.

From system of blood: infrequently anemia, Shenlyayna-Genokh's purpura.
Allergic reactions: less than 1% - urticaria, skin rash, an itch, a Quincke's disease (including the hypostasis of a throat and language causing obstruction of respiratory tracts and/or a face edema, lips, a throat). Sometimes the Quincke's disease developed earlier at reception of other medicines, including APF inhibitors.

From the central nervous system and sense bodys: 1% and more - dizziness, an adynamy, a headache, fatigue, sleeplessness; less than 1% - concern, a sleep disorder, drowsiness, dysmnesias, peripheral neuropathy, paresthesias, giposteziya, migraine, a tremor, an ataxy, a depression, a syncope, a ring in ears, disturbance of taste, a vision disorder, conjunctivitis.

From cardiovascular system: orthostatic hypotension (dozozavisimy), heartbeat, takhi-and bradycardia, arrhythmias, stenocardia, vasculitis.

From urinogenital system: less than 1% - imperative desires on an urination, infections of urinary tract, a renal failure, decrease in a libido, impotence.

From respiratory system: 1% and more - a nose congestion, cough *, infections of upper parts of respiratory tracts, pharyngitises, диспноэ, bronchitis, a rhinedema.

From a digestive tract: 1% and more - nausea, diarrhea *, the dispeptic phenomena *, an abdominal pain; less than 1% - anorexia, dryness in a mouth, a dentagra, vomiting, a meteorism, gastritis, a lock, hepatitis, an abnormal liver function.

From integuments: less than 1% - a xeroderma, an erythema, a photosensitization, the increased sweating, an alopecia.

From a musculoskeletal system: 1% and more - spasms, a mialgiya *, a dorsodynia, a thorax, legs; less than 1% - an arthralgia, arthritis, shoulder, knee pain, fibromyalgia.

Laboratory indicators: hyperpotassemia; infrequently: moderate increase in level of urea and creatinine in blood serum; very seldom: increase in activity of enzymes of a liver, hyperbilirubinemia.

Others: gout.

* - side effects which frequency of development is comparable to placebo are marked.

Interaction with other medicines:

Any clinically significant medicinal interactions with Hydrochlorthiazidum, digoxin, indirect anticoagulants, Cimetidinum, phenobarbital, ketokonazoly and erythromycin are noted. During a concomitant use with rifampicin and flukonazoly decrease in level of an active metabolite lozartana potassium was noted. Clinical effects of this phenomenon are not known.
The concomitant use with kaliysberegayushchy diuretics (for example, спнронолактон, Triamterenum, amiloride) and drugs of potassium increases risk of a hyperpotassemia.
At joint reception with non-steroidal anti-inflammatory drugs (NPVP), including the selection inhibitors of cyclooxygenase-2 can reduce effect of diuretics and other antihypertensives.
If lozartan it is appointed along with thiazide diuretics, decrease in the ABP lozartana potassium has the approximately additive character. Strengthens (mutually) effect of other antihypertensives (diuretics, beta adrenoblockers, sympatholytics).

Contraindications:

Hypersensitivity to lozartanu or to other components of drug, arterial hypotension, a hyperpotassemia, dehydration, pregnancy and the period of a lactation, age up to 18 years (efficiency and safety are not established), a lactose intolerance, a galactosemia or a syndrome of the broken absorption of a glucose/galactose.

With care: a liver and/or renal failure, reduced volume of the circulating blood, disturbances of water and electrolytic balance, a bilateral stenosis of renal arteries or a stenosis of an artery of the only kidney.

Pregnancy and period of a lactation
There are no data on use lozartana at pregnancy. Renal perfusion of a fruit which depends on development a system renin-angiotenzinovoy begins to function in the third trimester of pregnancy. The risk for a fruit increases at reception lozartana in the second and third trimesters. At pregnancy establishment therapy lozartanom has to be immediately stopped. There are no data on allocation lozartana in maternal milk. Therefore it is necessary to resolve an issue of the feeding termination by a breast or therapy cancellation lozartanom taking into account its importance for mother.

Overdose:

Symptoms: the expressed decrease in the ABP, tachycardia; as the result of parasympathetic (vagal) stimulation can develop bradycardia. Treatment: artificial diuresis, symptomatic therapy. The hemodialysis is inefficient.

Storage conditions:

List B. To store in the dry place at a temperature not above 30 °C. To store in the place, unavailable to children. A period of validity 2 years for tablets on 12,5 mg, 25 mg and 100 mg, 5 years for tablets on 50 mg. Not to use drug after expiry date.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, on 12,5 mg, 25 mg, 50 mg and 100 mg. On 7, 10, 14 tablets in a blister strip packaging. 2 blister strip packagings on 7 tablets, 1 blister strip packaging on 14 tablets, 3, 6 or 9 blister strip packagings on 10 tablets together with the application instruction place in a pack from a cardboard.