Ramizes

General characteristics. Structure:

Active ingredient: ramipril;

1 tablet contains a ramipril of 1,25 mg, 2,5 mg, 5 mg, 10 mg;

 excipients: tablets on 1,25 mg: Natrii hydrocarbonas, lactoses monohydrate, sodium of a kroskarmeloz, starch prezhelatinizirovanny 1500, magnesium stearate;

tablets on 2,5 mg: Natrii hydrocarbonas, lactoses monohydrate, sodium of a kroskarmeloz, starch prezhelatinizirovanny 1500, magnesium stearate, ferrous oxide yellow (Е 172);

tablets on 5 mg: Natrii hydrocarbonas, lactoses monohydrate, sodium of a kroskarmeloz, starch prezhelatinizirovanny 1500, magnesium stearate, ferrous oxide yellow (Е 172), ferrous oxide red (Е 172);

tablets on 10 mg: Natrii hydrocarbonas, lactoses monohydrate, sodium of a kroskarmeloz, starch prezhelatinizirovanny 1500, magnesium stearate.

Pharmacological properties:

Pharmacodynamics. Ramizes - anti-hypertensive means, APF inhibitor. Suppressing angiotensin II synthesis, drug reduces its vasopressor action and the stimulating influence on secretion of Aldosteronum. Increases activity of a renin in plasma, and also inhibits metabolism of bradikinin.

Reception of a ramipril causes noticeable decrease in resistance of peripheral arteries. Generally the renal plazmotok and a glomerular filtration rate significantly do not change. Introduction of a ramipril to patients with arterial hypertension leads to a lowering of arterial pressure in a prone position and standing, without the compensatory growth of heart rate. At most of patients the anti-hypertensive effect after oral administration of a single dose is shown in 1-2 hours. The maximum effect of a single dose is, as a rule, reached in 3-6 h and usually lasts 24 h. The maximum anti-hypertensive effect at long treatment ramiprily is observed in 3-4 weeks. At long therapy it remains for 2 years. In response to the sharp termination of reception of a ramipril there is no bystry and expressed growth of arterial pressure.

At patients with clinical displays of heart failure which treatment was begun in 3-10 days after an acute myocardial infarction ramiprit reduced risk of mortality by 27% in comparison with placebo. Also decrease in other risks, including risk of unexpected death (for 30%) and risk of progressing of a disease before development of serious/persistent heart failure was revealed (for 23%). Besides, the probability of late hospitalization in connection with heart failure decreased by 26%.

At patients with not diabetic or diabetic nephropathy ramiprit reduces the speed of a progression of a renal failure and approach of a final stage of a renal failure and thereof — the need for carrying out dialysis or transplantation of a kidney. At patients with not diabetic or diabetic initial nephropathy ramiprit reduces albumine excretion.

At patients who have the increased cardiovascular risk in connection with existence of diseases of vessels or a diabetes mellitus ramiprit reduces the frequency of approach of a myocardial infarction, stroke or cardiovascular death. Besides, ramiprit reduces the general mortality and emergence of need for carrying out revascularization, and also detains emergence and a progression of congestive heart failure. Ramipril reduces risk of development of a nephropathy in the general group of patients and at patients with diabetes. Ramipril also significantly reduces the frequency of emergence of a microalbuminuria. Such effects were observed at patients both with arterial hypertension, and with a normotenziya.

Pharmacokinetics. Presistemny metabolism of a ramipril happens to formation of an active metabolite of a ramiprilat in a liver. Except such activation with formation of a ramiprilat, ramiprit is exposed to a glyukuronization and turns in ramiprit diketopiperazine (ether). Ramiprilat also glyukuronizirutsya and turns in рамиприлат diketopiperazine (acid).

Bioavailability of a ramiprilat after oral administration of 2,5 and 5 mg of a ramipril makes about 45%. It is established that ramiprit gets into breast milk.

Ramipril is quickly absorbed after oral administration. Absorption of a ramipril makes not less than 56%. Reception of a ramipril together with food did not reveal considerable influence on absorption. The maximum plasma concentration of a ramipril is reached in 1 hour after oral administration. The elimination half-life of a ramipril makes about 1 hour. Peak concentration of a ramiprilat in a blood plasma is observed between 2 and 4 hours after oral administration of a ramipril.

Decrease in concentration of a ramiprilat in plasma happens in several phases. The half-cycle of an initial phase of distribution and elimination makes about 3 hours. After that there comes the transitional phase (with a half-cycle about 15 hours), and then — a final phase during which plasma concentration of a ramiprilat very low, with a half-cycle about 4-5 days.

Existence of a final phase is caused by slow dissociation of a ramiprilat from close, but saturated communication with APF.

Despite a long final phase of removal, after a single dose of a ramipril in a dose of 2,5 mg and above, steady state is reached already approximately in 4 days. After multiple dose the "effective" elimination half-life, depending on a dose, makes 13-17 hours. Time of dissociation of a ramiprilat with APF — 10,7 hours that testifies to high activity.

Linkng of a ramipril and ramiprilat with serum proteins makes about 73% and

56% respectively. At healthy volunteers at the age of 65-76 years the kinetics ramiprit and the ramiprilata is similar that at healthy volunteers of young age. At a renal failure removal of a ramiprilat decreases, the renal clearance of a ramiprilat decreases in proportion to clearance of creatinine. It causes increase in plasma concentration of a ramiprilat which decrease much more slowly, than at persons with normal function of kidneys. At introduction of high doses (10 mg), at liver depression of function, transformation of a ramipril in рамиприлат happens later, plasma concentration of a ramipril increase and removal of a ramiprilat is slowed down. As well as at healthy volunteers and patients with arterial hypertension, after oral administration of 5 mg of a ramipril of 1 times a day for 2 weeks at patients with congestive heart failure of considerable cumulation of a ramipril and ramiprilat it was not observed.

Pharmaceutical characteristics.

Main physical and chemical properties.

Tablets on 1,25 mg: tablets of a ploskotsilindrichesky form, white or almost white color with a facet, with a slight specific smell or inodorous. On a surface of tablets the insignificant mramornost is allowed;

tablets on 2,5 mg: tablets of a ploskotsilindrichesky form, light yellow color with a facet and risky, with a slight specific smell or inodorous. On a surface of tablets insignificant impregnations and a mramornost are allowed;

tablets on 5 mg: tablets of a ploskotsilindrichesky form, light pink color with a facet and risky, with a slight specific smell or inodorous. On a surface of tablets insignificant impregnations and a mramornost are allowed;

tablets on 10 mg: tablets of a ploskotsilindrichesky form, white or almost white color with a facet and risky, with a slight specific smell or inodorous. On a surface of tablets the insignificant mramornost is allowed.

Indications to use:

Arterial hypertension (as monotherapy or in a combination with other hypotensive drugs, for example, diuretics or antagonists of calcium).
Congestive heart failure (also in a combination with diuretics).
The congestive heart failure which arose for the first several days after an acute myocardial infarction.
Not diabetic or diabetic explicit glomerular or initial nephropathy.
Decrease in risk of a myocardial infarction, stroke or cardiovascular death at patients with the increased cardiovascular risk (the expressed coronary heart disease (with or without myocardial infarction in the anamnesis), a stroke in the anamnesis, a disease of peripheral vessels in the anamnesis or a diabetes mellitus with at least one accessory factor of cardiovascular risk (a microalbuminuria, arterial hypertension, the increased general level of cholesterol, low level of cholesterol of lipoproteins of high density, smoking)).

Route of administration and doses:

Ramizes accept irrespective of meal. It is necessary to swallow of tablets whole, without chewing, washing down with a large amount of water.

Treatment of arterial hypertension. The initial dose of drug usually makes 2,5 mg once a day. Further, in case of insufficient anti-hypertensive effect, the dose of drug is recommended to be increased by its doubling every 2-3 week. The usual maintenance dose makes 2,5-5 mg a day. The most admissible daily dose for adults - 10 mg. An alternative of increase in a dose over 5 mg of Ramizes a day can be additional use, for example, of diuretic or the antagonist of calcium.

Treatment of congestive heart failure. An initial dose - 1,25 mg once a day. At insufficient therapeutic effect the daily dose can be increased, doubling it each 1-2 weeks. If the necessary dose makes 2,5 mg of Ramizes or above, it can be accepted in the form of a single dose or to divide into two receptions. The maximum daily dose should not exceed 10 mg.

Treatment after an acute myocardial infarction. The initial daily dose makes 5 mg (on

2,5 mg in the morning and in the evening). At bad portability it is necessary to reduce this dose to 2,5 mg a day (on 1,25 mg in the morning and in the evening for two days).

Then, depending on reaction of the patient, the dose can be increased. It is recommended to increase a dose by its doubling every 1-3 day.

Further the general daily dose which was divided at first into two can be accepted disposable. The most admissible daily dose - 10 mg of Ramizes.

Experience of treatment of patients with heavy (degree IV on NYHA classification – the Yyu-Yorksky cordial association) heart failure right after a myocardial infarction has not enough. If it is decided to treat such patients this means, it is recommended to begin therapy with the smallest effective daily dose (1,25 mg of Ramizes once a day) and to carry out its any increase very carefully.

For decrease in risk of a myocardial infarction, a stroke or cardiovascular death at patients with the increased cardiovascular risk the recommended initial dose of Ramizes makes 2,5 mg once a day. The dose is gradually increased depending on portability of drug. It is recommended to double a dose in one week, and in three weeks to increase it to a usual maintenance dose – 10 mg once a day. Use of a dose over 10 mg was studied insufficiently once a day.

Use by patients with a heavy renal failure and clearance of creatinine

<36 ml/min. were investigated insufficiently.

Diabetic or not diabetic nephropathy. The initial dose of drug makes

1,25 mg a day. Depending on therapeutic effect the daily dose can increase to a maintenance dose which makes 5 mg once a day. Doses over 5 mg were studied insufficiently once a day.

Special categories of patients.

Elderly patients. An initial dose - 1,25 mg a day.

Dosing for patients with a renal failure. If the clearance of creatinine makes from 50 to 20 ml/min. on 1,73 sq.m of surface area of a body, the initial daily dose of 1,25 mg of Ramizes is usually applied. The most admissible daily dose in this case makes 5 mg of Ramizes.

Patients with an abnormal liver function. At patients with an abnormal liver function the maximum daily dose makes 2,5 mg. Such patients at early stages of treatment by Ramizes demand careful medical observation.

Patients with incompleteness the compensated insufficiency of liquid or salt in an organism, patients with the expressed arterial hypertension, as well as patients for whom hypotensive reaction can make extra risk (for example, with clinically significant stenosis of coronary vessels or vessels, krovosnabzhayushchy a brain): it is necessary to apply the reduced initial dose of 1,25 mg a day.

Patients who were treated previously by diuretics. It is desirable to stop reception of diuretics in 2-3 days or, depending on duration of effect of diuretic, even earlier, prior to treatment by Ramizes, or at least to lower a diuretic dose. The initial daily dose usually makes 1,25 mg.

At patients with arterial hypertension who are on a hemodialysis: ramiprit slightly gives in to dialysis. The initial dose makes 1,25 mg a day, and the maximum daily dose – 5 mg; drug needs to be used in several hours after a hemodialysis.

Features of use:

Ramizes it is necessary to apply under constant observation of the doctor.

At patients who were treated by APF inhibitors cases of a Quincke's disease of the person, extremities, lips, language, a glottis or throat were observed.

Urgent treatment of a Quincke's disease which threatens life includes urgent introduction of Epinephrinum (subcutaneously or slowly intravenously), in parallel with control of an ECG and arterial pressure. Hospitalization, observation of the patient for 12-24 hours at least is recommended. It is possible to write out it only after symptoms completely disappear.

At patients who were treated by APF cases of a Quincke's disease of intestines were observed. These patients complained of an abdominal pain (with or without nausea or vomiting); in certain cases also the Quincke's disease of the person was observed. Symptoms of a Quincke's disease of intestines disappeared after the termination of reception of APF inhibitors. There is no sufficient corresponding therapeutic experience of use of Ramizes to children, patients with a heavy renal failure (the clearance of creatinine is lower than 20 ml/min. on 1,73 sq.m of surface area of a body) and to the patients who are on dialysis.

Patients with a superactivity a system renin-angiotenzinovoy. At treatment of patients, with a superactivity a system renin-angiotenzinovoy, it is necessary to be especially careful. Such patients have risk of an unexpected and considerable lowering of arterial pressure and deterioration in function of kidneys as a result of APF inhibition, especially when APF inhibitor or the accompanying diuretic are appointed for the first time or for the first time in higher dose. In an initiation of treatment or at increase in a dose it is necessary to carry out by drug careful control of arterial pressure until there is a threat of its sharp decrease. Superactivity a renin-angiotenzinovoy of system can be expected, in particular at patients with heavy, especially malignant arterial hypertension; at patients with heart failure, especially with heavy, or such which was treated by other drugs which can reduce arterial pressure; patients with hemodynamically significant difficulty of inflow or outflow have blood from a left ventricle (for example, because of a stenosis of an aorta or a stenosis of the mitral valve or a hypertrophic cardiomyopathy); at patients with hemodynamically significant renal artery stenosis. This category of patients on an initial phase of treatment needs special medical observation. There can be a need to stop the begun treatment by diuretics: at patients who accepted previously diuretics. If the termination of reception or a dose decline of diuretic is impossible, in an initial phase of treatment strict medical observation is necessary; at patients with threat or disturbance of water and electrolytic balance (as a result of insufficient consumption of liquid or salt or, for example, in connection with diarrhea, vomiting or an excessive potovydeleniye, in cases when compensation of a lack of liquid and salt is insufficient).

Correction of a condition of dehydration, hypovolemia or deficit of salt prior to treatment is recommended (however for patients with heart failure such adjusting measures should be estimated carefully from the point of view of possible risk of a volume overload). At clinically significant states treatment by Ramizes can be begun or continued only when the appropriate measures according to the prevention of an excessive lowering of arterial pressure and depression of function of kidneys are at the same time applied.

Patients with liver diseases. Patients with an abnormal liver function can have a response to treatment by Ramizes either is raised, or lowered. Besides, at patients with heavy cirrhosis with hypostases and/or ascites activity the renin-angiotenzinovoy of system can be significantly raised. Therefore during treatment of these patients it is necessary to be especially careful.

Special medical control is necessary for patients for whom the considerable lowering of arterial pressure represents extra risk (for example, patients with hemodynamically significant stenosis of coronary arteries or vessels of a brain) in an initial phase of treatment.

Elderly people. Elderly people can have more expressed reaction to APF inhibitors. At the beginning of their treatment assessment of renal function is recommended. Monitoring of renal function. It is recommended to carry out monitoring of function of kidneys, first of all in the first weeks of treatment by APF inhibitor. Especially careful control is necessary for patients with heart failure; depression of function of kidneys; transplantirovanny kidney; a renovascular disease, including patients with hemodynamically significant unilateral renal artery stenosis. In the last group of patients even the insignificant growth of level of creatinine in blood serum can testify to unilateral depression of function of kidneys.

Combination with methods of extracorporal therapy. At Ramizes's reception it is impossible to carry out procedures of extracorporal therapy from which the contact of blood with negatively charged surfaces because of risk of development of a heavy acute anaphylaxis results. Therefore, at use of drug it is not necessary to carry out the procedure of dialysis or haemo filtering using weed (akrilonitrinovy, sodium-2-metilsulfonatnykh) membranes with high ultrafiltrational activity (for example, ""AN 69") and the procedure of an aferez LLD (lipoproteins of low density) using a sulfate dextran.

Hyperpotassemia. At some patients receiving APF inhibitors, including ramiprit, observed a hyperpotassemia. The risk of emergence of a hyperpotassemia is higher at patients with a renal failure, 70 years, with not controlled diabetes mellitus, at those who receive potassium salts, kaliysberegayushchy diuretics, and also other active agents increasing potassium level or at such states as dehydration, an acute cordial decompensation, a metabolic acidosis are more senior than persons. If combined use of the listed drugs is considered expedient, regular monitoring of level of potassium in blood serum is recommended.

Neutropenia/agranulocytosis. Neutropenia/agranulocytosis cases, and also thrombocytopenia and anemia are observed seldom. There are messages on a possibility of oppression of marrow. It is recommended to control quantity of white blood cells for identification of a possible leukopenia. It is necessary to carry out to a bowl hemolitic monitoring to patients with an impaired renal function, with the accompanying collagenoses (a system lupus erythematosus or a scleroderma) and in an initial phase of treatment or if the patient accepts other drugs which can cause change of a picture of blood.

Cough. At some patients at use of APF inhibitors cough is observed. It is characteristic that cough unproductive, persistent and passes after the therapy termination. The probability of the cough caused by APF inhibitors has to be considered when carrying out differential diagnosis of cough.

Drug contains lactose therefore patients should not appoint it with rare hereditary forms of intolerance of a galactose, deficit of lactase or a syndrome of glyukozo-galaktozny malabsorption.

Ability to influence speed of response at control of motor transport or work with other mechanisms. 

Some side effects (for example, some symptoms of a lowering of arterial pressure, in particular dizziness) can negatively influence ability of the patient to concentrate attention and speed of psychomotor reactions, especially in an initiation of treatment or upon transition from treatment by other drugs. After reception of the first dose or further increase in a dose it is not desirable to manage motor transport or to work with other mechanisms for several hours.

Side effects:

Side reactions are classified by emergence frequency: very often (≥1/10), it is frequent (from ≥1/100 to <1/10), infrequently (from ≥1/1000 to <1/100), is rare (from ≥1/10000 to <1/1000), is very rare (from ≥1/100000 to <1/10000), frequency is not determined (it is impossible to establish according to the available data).

From cardiovascular system: often – arterial hypotension, an orthostatic lowering of arterial pressure, a syncope; infrequently – myocardium ischemia, including stenocardia or a myocardial infarction, tachycardia, arrhythmia, a heart consciousness, peripheral hypostases, reddening; seldom – a stenosis of vessels, hypoperfusion, a vasculitis; very seldom – the short-term ischemic attack, an ischemic stroke; frequency is not determined – Reynaud's phenomenon.

From an urinary system: infrequently – a renal failure, including an acute renal failure, increase in amount of urine, aggravation of a background proteinuria, increase in level of urea of blood and creatinine.

From respiratory system: often – the unproductive, irritating cough, bronchitis, sinusitis; infrequently – a nose congestion, a bronchospasm, including an exacerbation of asthma; seldom - диспноэ.

From a digestive tract, a liver and a pancreas: often – an inflammation in an oral cavity and digestive tract, digestive disturbances, dyspepsia, diarrhea, nausea, vomiting; infrequently – increase in level of enzymes of a pancreas, a Quincke's disease of a small intestine, including gastritis, a lock, dryness in a mouth, increase in level of hepatic enzymes and/or conjugates of bilirubin; seldom – a glossitis, a sensation of discomfort in an abdominal cavity, a stomach ache, cholestatic jaundice, damage of hepatic cells; frequency is not determined – aphthous stomatitis; in isolated cases – pancreatitis, disturbance of perception of a smell and taste (for example, metal smack); sometimes - total loss of taste, an acute liver failure, cholestatic or cytolytic hepatitis – with a fatal outcome).

From a nervous system, sense bodys and mentality: often – a headache, dizziness; infrequently – вертиго, paresthesia, an ageusia, a dysgeusia, a vision disorder, including a sight illegibility, decrease in mood, alarm, nervousness, concern, a sleep disorder, including a somnolention; seldom – a tremor, disorder of balance, conjunctivitis, a hearing disorder, a ring in ears, confusion of consciousness; frequency is not determined – cerebral ischemia, including an ischemic stroke and the tranzitorny ischemic attack, disturbance of psychomotor functions, a burning sensation, a parosmiya, disturbance of attention.

Allergic and immunopathological reactions: frequency is not determined – anaphylactic and anaphylactoid reactions, increase in level of anti-nuclear antibodies.

Reactions from skin: often – rash, an itch, urticaria; infrequently – the Quincke's disease, obstruction of respiratory tracts owing to a Quincke's disease can have fatal effects, пруритус, a hyperhidrosis; seldom – exfoliative dermatitis, an urtikariya, an onycholysis; very seldom – photosensitivity reaction; frequency is not determined – makulopapulyozny rash, a pemphigus, a toxic epidermal necrolysis, Stephens-Johnson's syndrome, a multiformny erythema, a pempigus, an aggravation of a course of psoriasis, psoriasis dermatitis, a pemfigoidny or lichenoid dieback or an enantema, an allopecia.

Musculoskeletal frustration and frustration from connecting fabric: often – muscular spasms, a mialgiya; infrequently – an arthralgia.

Disorders of metabolism and food: often – increase in level of potassium in blood; infrequently – anorexia, a loss of appetite; frequency is not determined – decrease in level of sodium in blood.

From system of a hemopoiesis and lymphatic system: infrequently – an eosinophilia; seldom – reduction of quantity of white cells (including a neutropenia and an agranulocytosis), reduction of quantity of red cells, decrease in level of hemoglobin, reduction of quantity of thrombocytes; frequency is not determined – insufficiency of marrow, a pancytopenia, hemolitic anemia.

General frustration: often – thorax pain, an adynamy; infrequently – a pyrexia; seldom – weakness, drowsiness, fatigue.

Frustration from reproductive function and mammary glands: infrequently – tranzitorny erectile dysfunction, impotence, decrease in a libido;

frequency is not determined - a gynecomastia.

Interaction with other medicines:

To apply with care. Anti-hypertensive medicines (for example, diuretics) and other drugs are capable to reduce arterial pressure (for example, nitrates, tricyclic antidepressants, anesthetics): it is necessary to expect strengthening of hypotensive effect of a ramipril. It is regularly recommended to control serumal concentration of sodium at patients who at the same time receive treatment by diuretics.

Vasoconstrictive sympathomimetics can weaken effect of a lowering of arterial pressure of Ramizes. It is recommended to control arterial pressure especially carefully.

Allopyrinolum, immunodepressants, corticosteroids, procaineamide, cytostatics and other medicines which can cause changes in a gemogramma can increase probability of emergence of hematologic reactions at simultaneous use with ramiprily.

Lithium salts. Lithium excretion under the influence of APF inhibitors can decrease. Such decrease can lead to growth of concentration of lithium in blood serum and to increase in toxicity of lithium. In this regard it is necessary to control concentration of lithium. Antidiabetic means (for example, insulin and derivatives of sulphonylurea). APF inhibitors can increase effect of insulin. In some cases it can lead to development of hypoglycemic reaction in patients who at the same time apply antidiabetic means. In an initiation of treatment especially careful monitoring of level of glucose in blood is recommended.

Non-steroidal anti-inflammatory drugs (NPVS). Easing of effect of pressure decrease of blood under the influence of Ramizes is possible. Besides, simultaneous treatment by APF and NPVS inhibitors can cause increase in risk of depression of function of kidneys and increase in level of potassium in blood serum.

Heparin. Increase in potassium concentration in blood serum is possible.

Alcohol. Vasodilatation increases. Ramizes can strengthen effect of alcohol.

The increased consumption of salt can weaken anti-hypertensive action of Ramizes.

Owing to inhibition of APF the probability of emergence and weight of anaphylactic and anaphylactoid reactions to poison of insects increases. It is considered that such effect can be also observed and concerning other allergens.

Contraindications:

Hypersensitivity to other APF inhibitors or to any of drug components;
Quincke's disease in the anamnesis;
renal artery stenosis (unilateral or bilateral);
hypotensive or hemodynamically unstable states;
primary hyper aldosteronism;
pregnancy, feeding period breast;
children's age.
During Ramizes's reception it is impossible to carry out the procedure of dialysis or haemo filtering using weed (akrilonitrinovy, sodium-2-metilsulfonatnykh) membranes with high ultrafiltrational activity (for example, ""AN 69") and the procedure of an aferez LLD (lipoproteins of low density) using a sulfate dextran because of risk of development of a heavy acute anaphylaxis.

Overdose:

Symptoms. The overdose can cause excessive expansion of peripheral vessels (with the expressed arterial hypotension, shock), bradycardia, disturbance of balance of electrolytes and a renal failure.

Treatment. The general actions (a gastric lavage, reception of absorbent carbon and sodium of sulfate if it is possible, for the first 30 min.). At arterial hypotension in addition to the actions directed to recovery of volume of liquid and salt balance it is necessary to apply agonists α1-адренергических receptors (for example, Norepinephrinum, a dopamine).

There are no data on efficiency of an artificial diuresis, change рН urine, haemo filtering or dialysis, from the point of view of acceleration of elimination of a ramipril or a ramiprilat.

Use during pregnancy or feeding by a breast.  

 

Ramizes is contraindicated at pregnancy. Before its use it is necessary to exclude pregnancy, and also to prevent its approach, using an adequate method of contraception. If pregnancy occurred during Ramizes's reception, it should be replaced with the drug which is not containing APF inhibitor at once.

Feeding by a breast is a contraindication for drug use.

Children.

 

Due to the lack of sufficient clinical experience Ramizes children cannot appoint.

Storage conditions:

 Period of storage. 2 years. Tablets on 1,25 mg – 1 year 6 months. Not to use drug after the termination of the period of validity specified on packaging. To store in the unavailable to children, protected from light place at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in the blister. On 1 or 3 blisters enclosed in a pack.