Лориста® N

General characteristics. Structure:

Active agents: лозартан potassium of 50 mg; hydrochlorothiazide of 12,5 mg
Excipients: starch prezhelatinizirovanny, cellulose microcrystallic, lactoses monohydrate, magnesium stearate.
COVER:
gipromelloza, macrogoal 4000, dye quinolinic yellow, E104, titanium dioxide, El71, talc.

Description
Oval, slightly biconvex tablets, film coated from color, yellow to yellow with a greenish shade, with risky on one party.

Pharmacological properties:

Pharmacodynamics. Lorista of N - the combined drug; has hypotensive effect.

Lozartan is the selection antagonist of receptors of angiotensin II (AT1 type) for intake, the nonprotein nature. In vivo and in vitro лозартан 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 AT2-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 of a lozartan 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 лозартан does not exert clinically significant impact on the heart rate (HR). Lozartan is effective at men and women, and also at elderly (> 65 years) and younger patients (<65 years).

Hydrochlorothiazide. Thiazide diuretic which diuretic effect is connected with disturbance of a reabsorption of ions of sodium, chlorine, potassium, magnesium, water in distal department of nephron; removal of calcium ions, uric acid detains. Has anti-hypertensive properties; hypotensive action develops due to expansion of arterioles. Practically does not exert impact on the normal arterial pressure (AP). The diuretic effect occurs in 1-2 hours, reaches a maximum in 4 hours and 6-12 hours proceed. Anti-hypertensive action comes in 3-4 days, but for achievement of optimum therapeutic effect 3-4 weeks can be required.

Pharmacokinetics. The pharmacokinetics of a lozartan and hydrochlorothiazide at a concomitant use does not differ from that at their separate appointment.

Lozartan.
Lozartan 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. Tstakh-1 hour after intake, and its active metabolite (EHR-3174) - 3-4 hours.

More than 99% of a lozartan and EHR-3174 contact proteins of a blood plasma, preferential, albumine. The volume of distribution of a lozartan is equal to 34 l. Very badly gets through a blood-brain barrier.

Lozartan 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 of a lozartan 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 of a lozartan 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 of a lozartan and an active metabolite makes 2 hours and 6-9 hours, respectively. It is removed preferential with bile of-58%, kidneys - 35%.

Hydrochlorothiazide
After intake absorption of a hydrochlorothiazide makes 60-80%. The maximum concentration of a hydrochlorothiazide in blood is reached in 1-5 hours after intake.

Communication with proteins of a blood plasma of a hydrochlorothiazide - 64%. The hydrochlorothiazide is not metabolized and quickly removed through kidneys. The elimination half-life makes 5-15 hours.

Indications to use:

• Arterial hypertension (patients to whom the combination therapy is shown).
• Decrease in risk of cardiovascular incidence and mortality at patients with arterial hypertension and a hypertrophy of a left ventricle.

Route of administration and doses:

Inside, irrespective of meal. Lorist of N can combine with other anti-hypertensive means.

Arterial hypertension
The initial and maintenance dose makes 1 tablet of Lorista of N (50/12,5 mg) of 1 times a day. The maximum anti-hypertensive effect is reached within three weeks of therapy. For achievement of more expressed effect increase in a dose of drug up to 2 tablets of Lorista of N (50/12,5 mg) of 1 times a day is possible. The maximum daily dose - 2 tablets of drug of Lorist N.

At patients with a reduced volume of the circulating blood (for example, against the background of reception of high doses of diuretics) the recommended initial dose of a lozartan at patients with a hypovolemia makes 25 mg once a day. In this regard therapy of N by Lorista needs to be begun after cancellation of diuretics and correction of a hypovolemia.

Correction of an initial dose is not required from elderly patients and patients with a moderate renal failure, including being on dialysis.

Decrease in risk of cardiovascular incidence and mortality at patients with arterial hypertension and a hypertrophy of a left ventricle

The standard initial dose of a lozartan makes 50 mg of 1 times a day. Patients at whom it was not succeeded to reach the target objectives of the ABP against the background of reception of a lozartan of 50 mg/days need selection of therapy by a combination of a lozartan with low doses of a hydrochlorothiazide (12,5 mg), and, in case of need, it is necessary to increase a dose of a lozartan to 100 mg in combination with a hydrochlorothiazide in a dose of 12,5 mg/days, further - to increase to 2 tablets of Lorista of N 50/12,5 mg of all (100 mg of a lozartan and 25 mg of a hydrochlorothiazide a day once).

Features of use:

It is possible to appoint together with other antihypertensives.

There is no need for special selection of an initial dose by the patient of advanced age. Drug can increase concentration of urea and creatinine in a blood plasma at patients with a bilateral stenosis of renal arteries or a renal artery stenosis of the only kidney.

The hydrochlorothiazide can strengthen arterial hypotension and disturbances of water and electrolytic balance (reduction of volume of the circulating blood, a hyponatremia, a gipokhloremichesky alkalosis, a hypomagnesiemia, a hypopotassemia), to break tolerance to glucose, to reduce removal of calcium with urine and to cause passing, slight increase of concentration of calcium in a blood plasma, to increase concentration of cholesterol and triglycerides, to provoke emergence of a hyperuricemia and/or gout. Reception of the medicines which are directly operating on system a renin angiotensin during II and III trimesters of pregnancy can lead to death of a fruit. At emergence of pregnancy drug withdrawal is shown.

Use of diuretics usually is not recommended to pregnant women in connection with risk of developing of jaundice at a fruit and the newborn, thrombocytopenia at mother. Therapy by diuretics does not prevent development of toxicosis of pregnancy.

The special preventions concerning excipients:
Lorista of N contains lactose therefore it cannot be appointed at the following states: deficit of lactase, galactosemia or sprue of a glucose/galactose.

Influence on ability to drive the car and other mechanisms
Practically all patients during therapy of N by Lorista can perform the tasks requiring special attention (for example, driving). At individuals at the beginning of therapy drug can cause to affect, thus, indirectly decrease in the ABP and dizziness their psychoemotional state. For safety, before the activity requiring special attention, patients have to estimate at first the reaction to the carried-out treatment.

Side effects:

From blood and lymphatic system: infrequently: anemia, Shenleyn-Genokh's purpura.

From immune system:
seldom: anaphylactic reactions, a Quincke's disease (including hypostasis of a throat and language,
causing obstruction of respiratory tracts and/or face edema, lips, a throat).

From TsNS and peripheral nervous system: 
often: headache, rotatory and not rotatory vertigo, sleeplessness, fatigue;
infrequently: migraine.

From cardiovascular system:
often: orthostatic hypotension (dozozavisimy), heartbeat, tachycardia;
seldom: vasculites.

From respiratory system:
often: cough, infections of upper parts of respiratory tracts, pharyngitises, rhinedema.

From digestive tract:
often: diarrhea, dyspepsia, nausea, vomiting, abdominal pain.

From gepatobiliarny system:
seldom: hepatitis, abnormal liver function.

From integuments and a hypodermic fatty tissue:
infrequently: urticaria, skin itch.

From a musculoskeletal system and connecting fabric:
often: mialgiya, dorsodynia;
infrequently: arthralgias.

Others:
often: adynamy, weakness, peripheral hypostases, stethalgia.

Laboratory indicators:
often: a hyperpotassemia, increase in concentration of hemoglobin and a hematocrit (clinically it is not significant);
infrequently: moderate increase in level of urea and creatinine in blood serum;
very seldom: increase in activity of enzymes of a liver and bilirubin.

Interaction with other medicines:

Lozartan
In clinical trials of interactions of pharmacokinetics clinically significant interactions of drug with a hydrochlorothiazide, digoxin, warfarin, Cimetidinum, phenobarbital, ketokonazoly and erythromycin are not revealed. Rifampicin and флуконазол reduce the level of an active metabolite (clinically this interaction is not studied).

The combination of a lozartan to kaliysberegayushchy diuretics (Spironolactonum, Triamterenum, amiloride), kaliysberegayushchy additives or salts of potassium can lead to a hyperpotassemia.

NPVP, including the selection inhibitors of cyclooxygenase-2 can reduce effect of diuretics and other antihypertensives, including лозартан. At the patients with an impaired renal function receiving therapy of NPVP (including cyclooxygenase-2 inhibitors), therapy by antagonists of receptors of angiotensin II can lead to further deterioration in function of kidneys, including an acute renal failure which is usually reversible.

The hypotensive effect of a lozartan, as well as other antihypertensives, can be reduced at indometacin reception.

Hydrochlorothiazide
With thiazide diuretics such medicines as ethanol, barbiturates and drugs, can exponentiate risk of development of orthostatic hypotension.

Hypoglycemic means (for intake and insulin) - dose adjustment of hypoglycemic means can be required.
Other antihypertensives - the additive effect.
Colestyraminum and колестипол - in the presence of anion exchange pitches absorption of a hydrochlorothiazide is broken.

Corticosteroids, AKTG (adrenocorticotropic hormone) - the expressed decrease in levels of electrolytes, in particular a hypopotassemia.

Pressory amines (for example, Epinephrinum, Norepinephrinum) - decrease in expressiveness of the response to reception of pressor amines.

Muscle relaxants of not depolarizing action type (for example, tubocurarine) - strengthening of effect of muscle relaxants.

Lithium - diuretics reduce renal clearance of lithium and increase risk of development of toxic effect of lithium; simultaneous use is not recommended.

NPVP (including cyclooxygenase-2 inhibitors) - can reduce diuretic, natriuretic and hypotensive effect of diuretics.

Due to the influence on calcium metabolism their reception can distort results of a research of function of epithelial bodies.

Contraindications:

Hypersensitivity to a lozartan, to means, the being derivatives of sulfonamides and to other components of drug, an anury, the expressed renal failures (the clearance of creatinine (CC) less than 30 ml/min.), a hyperpotassemia, dehydration (including against the background of reception of high doses of diuretics), the expressed abnormal liver functions, a refractory hypopotassemia, pregnancy, the lactation period, arterial hypotension, age up to 18 years (efficiency and safety are not established), deficit of lactase, a galactosemia or a sprue of a glucose/galactose.

With care: disturbances of water and electrolytic balance of blood (a hyponatremia, a gipokhloremichesky alkalosis, a hypomagnesiemia, a hypopotassemia), a bilateral stenosis of renal arteries or a stenosis of an artery of the only kidney, a diabetes mellitus, a hypercalcemia, a hyperuricemia and/or gout, the burdened allergological anamnesis (at some patients the Quincke's disease developed earlier at reception of other medicinal substances, including APF inhibitors) and bronchial asthma, general diseases of blood (including a system lupus erythematosus), co-administration of non-steroidal anti-inflammatory drugs (NPVP), including, cyclooxygenase-II inhibitors (SOH-2 inhibitors).

Use at pregnancy and in the period of a lactation
There are no data on use of a lozartan 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 of a lozartan in the second and third trimesters. At pregnancy establishment therapy of N by Lorista has to be immediately stopped. In need of purpose of drug in the period of a lactation it is necessary to stop breastfeeding.

Overdose:

Lozartan
Symptoms: the expressed decrease in the ABP, tachycardia; the bradycardia caused by parasympathetic (vagal) stimulation.
Treatment: the artificial diuresis, symptomatic therapy, a hemodialysis is inefficient.

Hydrochlorothiazide
Symptoms: the most frequent symptoms are a consequence of deficit of electrolytes (a hypopotassemia, a hypochloraemia, a hyponatremia) and dehydrations owing to an excessive diuresis. At a concomitant use of cardiac glycosides the hypopotassemia can aggravate the course of arrhythmias.
Treatment: symptomatic.

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. Period of validity 3 years. Not to use after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 50 mg + 12,5mg.
On 7, 10 or 14 tablets in the blister.
On 2,4, 8, 12 or 14 blisters (the blister on 7 tablets) together with the application instruction in a cardboard pack.
On 3, 6 or 9 blisters (the blister on 10 tablets) together with the application instruction in a cardboard pack.
On 1, 2, 4, 6 or 7 blisters (the blister on 14 tablets) together with the application instruction in a cardboard pack.