Lozap plus

General characteristics. Structure:

Active agents: lozartana of potassium of 50 mg and hydrochlorothiazide of 12,5 mg

Excipients
Mannitolum, cellulose microcrystallic, croscarmellose sodium, povidone, magnesium stearate, a gipromelloza 2910/5, a macrogoal 6000, talc, an emulsion simetikona, Opaspry yellow M-1-22801 (Opaspray yellow M-1-22801) (which part is: the water purified titanium the dioxide, ethanol denatured (alcohol metilirovanny BP) (99% etanol:1% methanol), a gipromelloza, dye Quinolinic yellow (Quinolin Yellow) (E 104), dye Crimson [Ponso 4R] (Pounceau 4R) (E 124)).

DESCRIPTION 
Oblong tablets of light yellow color, film coated, with dividing in half risky on both parties.

Pharmacological properties:

Pharmacodynamics. The combined drug, has hypotensive effect. Contains лозартан potassium - the antagonist of receptors of angiotensin II (AT1 subtype) and a hydrochlorothiazide - diuretic.
Lozartan is a specific antagonist of receptors of angiotensin II (AT1 subtype). Does not suppress a kinase of II - the enzyme destroying bradykinin. Reduces the general peripheric vascular resistance (GPVR), concentration in blood of adrenaline and Aldosteronum, the arterial pressure (AP), 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 chronic heart failure.
Hydrochlorothiazide - thiazide diuretic. Reduces Na+ reabsorption, strengthens allocation with K+ urine, a hydrocarbonate and phosphates. Lowers the ABP due to reduction of the volume of the circulating blood (VCB), change of reactivity of a vascular wall, decrease in pressor influence of vasoconstrictive substances and strengthening of depressor influence on a ganglion.

Pharmacokinetics. Lozartan is quickly absorbed from digestive tract. Bioavailability - about 33%. Has effect of "the first passing" through a liver, it is metabolized by a carboxylation with formation of an active metabolite. Communication with proteins of a blood plasma - 99%. Time of achievement of the maximum concentration of a lozartan makes 1 h, an active metabolite of 3 - 4 h, after intake. Elimination half-life of 1,5 - 2 h, and its main metabolite of 3 - 4 h, respectively. About 35% of a dose are removed with urine, about 60% - through intestines.
The hydrochlorothiazide is quickly absorbed from digestive tract. The elimination half-life makes 5,8 - 14,8 h. It is not metabolized by a liver. About 61% are removed by kidneys in not changed look.

Indications to use:

- Arterial hypertension (at patients for whom the combination therapy is optimum);
- Decrease in risk of cardiovascular diseases and mortality at patients with arterial hypertension and a hypertrophy of a left ventricle.

Route of administration and doses:

Inside, regardless of meal.

Arterial hypertension
The usual initial and maintenance dose of drug LOZAP PLUS makes 1 tablet a day. For those patients from whom at this dosage it is not possible to achieve adequate control of the ABP a dose LOZAPA PLUS can be increased to 2 tablets once a day.
The maximum dose makes 2 tablets once a day. In general, the maximum hypotensive effect is reached within 3 weeks after an initiation of treatment. There is no need for special selection of an initial dose to patients of elderly age.

Decrease in risk of cardiovascular diseases and mortality at patients with arterial hypertension and a hypertrophy of a left ventricle
Standard initial dose ЛОЗАПа (lozartana) 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 ЛОЗАПа (lozartan) of 50 mg/days need selection of therapy by a combination of a lozartan with low doses of a hydrochlorothiazide (12,5 mg) - LOZAP PLUS, and, in case of need, it is necessary to increase a dose to 2 tablets of drug LOZAP PLUS (only 100 mg of a lozartan and 25 mg of a hydrochlorothiazide a day once).

Features of use:

LOZAP PLUS it is possible to appoint together with other antihypertensives.
There is no need for special selection of an initial dose by the patient of elderly 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 Ca2 + with urine and to cause passing slight increase of concentration of Ca2 + 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 ренинангиотензин 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 of mother. Therapy by diuretics does not prevent development of toxicosis of pregnancy.
There is no information on influence on ability to drive the car and other mechanisms.

Side effects:

Side reactions are limited observed earlier at use of a lozartan of potassium and/or a hydrochlorothiazide. At treatment of essential hypertensia refer dizziness to the most frequent side effects.
Allergic reactions: a Quincke's disease, including hypostasis of a throat and/or language that led to obstruction of respiratory tracts, and/or a face edema, lips, the drinks and/or language which were occasionally noted at reception of a lozartan. Some of these patients had a Quincke's disease earlier at use of other drugs including APF inhibitors. Extremely seldom at reception of a lozartan manifestations of a vasculitis, including Shenlyayn-Genokh's disease were noted.
From cardiovascular system: decrease in the ABP.
From a digestive tract: at reception of a lozartan were registered rare (<1%) hepatitis cases, diarrhea.
From a respiratory organs: at reception of a lozartan - cough.
From integuments: small tortoiseshell.
Laboratory indicators: seldom (<1%) hyperpotassemia (serum potassium more than 5,5 mmol/l), increase in activity of "hepatic" transaminases.

Interaction with other medicines:

Lozartan strengthens effect of other antihypertensives. Clinically significant interaction with a hydrochlorothiazide, digoxin, indirect anticoagulants, Cimetidinum, phenobarbital, ketokenazoly, erythromycin is noted. As well as other drugs blocking angiotensin II or its effect, co-administration of kaliysberegayushchy diuretics (for example, Spironolactonum, Triamterenum, amiloride), drugs of potassium or the deputies of salt containing potassium can lead to a hyperpotassemia.
Hydrochlorothiazide
The following medicines can interact with thiazide diuretics at appointment, simultaneous with them:
Barbiturates, narcotic analgetics, ethanol - there can be a potentiation of orthostatic hypotension.
Hypoglycemic means (peroral means and insulin) - dose adjustment of hypoglycemic means can be required.
Other antihypertensives - the additive effect is possible.
Colestyraminum reduces absorption of a hydrochlorothiazide.
Corticosteroids, AKTG - strengthening of loss of electrolytes, in particular potassium.
Pressor amines - perhaps insignificant decrease in effect of pressor amines which is not interfering their use.
Not depolarizing muscle relaxants (for example, tubocurarine) - strengthening of action of muscle relaxants is possible.
Lithium drugs - diuretics reduce renal clearance of Li + and increase risk of intoxication lithium therefore simultaneous use is not recommended.
Non-steroidal anti-inflammatory drugs (NPVP) - at some patients, use of NPVP can reduce diuretic, natriuretic and hypotensive effects of diuretics.

Impact on results of laboratory researches
Thanks to impact on excretion of calcium, a tiazida can influence results of the analysis of function of parathyroid glands.

Contraindications:

- hypersensitivity to drug components;
- anury;
- the expressed arterial hypotension;
- the expressed abnormal liver functions and kidneys (clearance of creatinine? 30 ml / c);
- a hypovolemia (including against the background of high doses of diuretics);
- pregnancy and period of a lactation;
- age up to 18 years (efficiency and safety are not established).

With ostorozhnostyyupatsiyenta with a bilateral renal stenosis or a stenosis of an artery of the only kidney.
With care drug is appointed at patients with a diabetes mellitus, hypercalcemia, hyperuricemia and/or gout, and also to patients with the burdened allergological anamnesis and bronchial asthma, and also at general diseases of connecting fabric (including a system lupus erythematosus).

Overdose:

Symptoms: лозартан - the expressed decrease in the ABP, tachycardia, bradycardia (as a result of vagal stimulation). A hydrochlorothiazide - loss of electrolytes (a hypopotassemia, a hyperchloremia, a hyponatremia), and also dehydration arising owing to an excess diuresis.
Treatment: symptomatic and maintenance therapy. If drug is accepted recently, it is necessary to wash out a stomach; if necessary carry out correction of water and electrolytic disturbances.
Lozartan and his active metabolites are not removed by means of a hemodialysis.

Storage conditions:

List B. To store at a temperature not above 30 °C. To store in the place, unavailable to children! Period of validity 2 years. Drug cannot be used after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets film coated 50 mg / 12,5 mg. On 14 tablets in the blister from a foil of Al/PVC. On 2 blisters together with the application instruction place in a cardboard pack.
On 10 tablets in the blister from a foil of Al/PVC, on 1, 3 or 9 blisters (10, 30 or 90 tablets) together with the application instruction place in a cardboard pack.