Берлиприл®

General characteristics. Structure:

1 tablet of the drug Берлиприл® 5/10/20 contains active agent - enalapril a maleate 5/10 / 20 mg. respectively.

Excipients:

ÜÑÓ½¿»Ó¿½® 5

gelatin, lactoses monohydrate, magnesium stearate, magnesium carbonate the main, silicon dioxide colloid, sodium salt of carboxymethylstarch.

ÜÑÓ½¿»Ó¿½® 10/20

lactoses monohydrate, magnesium carbonate easy, gelatin, carboxymethylstarch sodium salt, magnesium stearate, brown iron oxide pigment (Е 172).

Pharmacological properties:

Pharmacodynamics. Enalapril - anti-hypertensive drug, from group of APF inhibitors. Enalapril is "pro-medicine": as a result of its hydrolysis enalaprilat which inhibits APF is formed. The mechanism of its action is connected with reduction of education from angiotensin I of angiotensin II which decrease in contents leads to direct reduction of allocation of Aldosteronum. At the same time the general peripheric vascular resistance, the systolic and diastolic arterial pressure (AP) goes down, post preload of a myocardium.

Expands arteries more than veins, at the same time reflex increase in heart rate is not noted.

The hypotensive effect is more expressed at the high level of a renin of a blood plasma, than at normal or its reduced level. Decrease in the ABP in therapeutic limits does not exert impact on cerebral circulation, the blood stream in vessels of a brain is supported at the sufficient level and against the background of reduced arterial pressure. Strengthens a coronary and renal blood stream.

At prolonged use the hypertrophy of a left ventricle of a myocardium and myocytes of walls of arteries of resistive type decreases, prevents to progress heart failure and slows down development of dilatation of a left ventricle. Improves blood supply of an ischemic myocardium. Reduces aggregation of thrombocytes.

Has some diuretic effect.

Time of approach of hypotensive effect at intake - 1 h, reaches a maximum in 4-6 h and remains to 24 h. At some patients therapy for several weeks is necessary for achievement of optimum level of arterial pressure. At heart failure the noticeable clinical effect is observed at prolonged treatment - 6 months and more.

Pharmacokinetics. After intake 60% of drug are absorbed. Meal does not influence enalapril absorption.

Enalapril to 50% contacts proteins of a blood plasma. Enalapril is quickly metabolized in a liver with formation of an active metabolite of enalaprilat which is more APF active inhibitor, than enalapril. Bioavailability of drug of 40%.

The maximum concentration of enalapril in a blood plasma is reached in 1 h, enalaprilat - 3-4 h. Enalaprilat easily passes through gistogematichesky barriers, excepting hematoencephalic, a small amount gets through a placenta and into breast milk.

Enalaprilat elimination half-life about 11 h. Enalapril preferential by kidneys - 60% is removed (20% - in the form of enalapril and 40% - in the form of enalaprilat). through intestines - 33% (6% - in the form of enalapril and 27% - in the form of enalaprilat).

Is removed at a hemodialysis (speed of 62 ml/min.) and peritoneal dialysis.

Indications to use:

- arterial hypertension (including renovascular hypertensia),
- at chronic heart failure (as a part of a combination therapy),
- asymptomatic dysfunction of a left ventricle (as a part of a combination therapy).

Route of administration and doses:

Берлиприл® appoint inside irrespective of meal time.

At monotherapy of arterial hypertension - an initial dose of 5 mg of 1 times a day (1 tablet Берлиприл® 5, 1/2 of the tablet Берлиприл® 10, 1/4 of the tablet Берлиприл® 20).

In the absence of clinical effect in 1-2 weeks the dose is raised on 5 mg. After reception of an initial dose patients have to be under medical observation during 2 h and in addition 1 h the ABP is not stabilized yet. If necessary and rather good tolerance, the dose can be increased to 40 mg/days in 2 receptions (8 tablets Берлиприл® 5, 4 of the tablet Берлиприл® 10, 2 of the tablet Берлиприл® 20). In 2-3 weeks pass to a maintenance dose - 10-40 mg/days, divided into 1-2 receptions. At moderate arterial hypertension the average daily dose makes about 10 mg (2 tablets Берлиприл® 5, 1 the tablet Берлиприл® 10, 1/2 the tablet Берлиприл® 20).

The maximum daily dose of drug makes 40 mg/days.

In case of appointment the patients who are at the same time receiving diuretics, treatment by diuretic need to stop in 2-3 days prior to purpose of Berlipril®. If it is impossible, then the initial dose of drug has to make 2,5 mg/days.

The patient with a hyponatremia (concentration of ions of sodium in blood serum less than 130 mmol/l) or concentration of creatinine in blood serum more than 0,14 mmol/l an initial dose - 2,5 mg of 1 times a day.

At renovascular hypertensia an initial dose - 2,5-5 mg/days. The maximum daily dose - 20 mg (4 tablets Берлиприл® 5, 2 of the tablet Берлиприл® 10, 1 the tablet Берлиприл® 20).

At chronic heart failure an initial dose of Berlipril® – 2,5 mg once, then increase a dose by 2,5-5 mg every 3-4 day according to clinical reaction to the most tolerable doses depending on the size of arterial pressure, but it is not higher than 40 mg/days once or in 2 receptions. At patients with low systolic pressure (less than 110 mm hg) therapy it is necessary to begin 1,25 mg with a dose. Selection of a dose has to be carried out during 2-4 weeks or to shorter terms. An average maintenance dose - 5-20 mg/days for 1-2 receptions.

At elderly more expressed hypotensive effect and lengthening of time of effect of drug is more often observed that it is connected with reduction of speed of removal of enalapril therefore the recommended initial dose elderly – 1,25 mg.

At asymptomatic dysfunction of a left ventricle - on 2,5 mg 2 times a day. The dose is selected taking into account portability to 20 mg/days, divided into 2 receptions.

At a chronic renal failure cumulation comes at decrease in filtering less than 10 ml / is lovely. At the clearance of creatinine (CC) of 80-30 ml/min. the dose usually makes 5-10 mg/days at KK to 30-10 ml/min. - 2,5-5 mg/days, at KK less than 10 ml/min. - 1,25-2,5 mg/days only in days of dialysis. Duration of treatment depends on efficiency of therapy. At too expressed decrease in the ABP the drug dose is gradually reduced.

Drug is used both in monotherapy, and in combination with other anti-hypertensive means.

Features of use:

It is necessary to be careful at appointment to patients with the reduced volume of the circulating blood (as a result of therapy by diuretics, at restriction of consumption of table salt, carrying out a hemodialysis, diarrhea and vomiting) - the risk of the sudden and expressed lowering of arterial pressure after use even of an initial dose of APF inhibitor is increased.

Tranzitorny hypotension is not a contraindication for treatment continuation by drug after stabilization of the arterial pressure (AP). In case of the repeated expressed decrease in the ABP it is necessary to reduce a dose or to cancel drug.

At development of an excessive lowering of arterial pressure of the patient transfer to horizontal position with a low headboard, if necessary enter normal saline solution and plasma substituting drugs.

Use of high-flowing dialysis membranes increases risk of development of anaphylactic reaction. Correction of the mode of dosing in days, free from dialysis, has to be carried out depending on the level of arterial pressure. Before treatment by APF inhibitors control of arterial pressure, blood indicators (hemoglobin, potassium, creatinine, urea, activity of "hepatic" enzymes), a squirrel in urine is necessary.

It is necessary to watch carefully patients with heavy heart failure, coronary heart disease and diseases of vessels of a brain at which the sharp lowering of arterial pressure can lead to a myocardial infarction, a stroke or a renal failure. Sudden cancellation of treatment does not lead to a syndrome of "cancellation" (sharp raising of the ABP).

Patients with the instruction on development of a Quincke's disease in the anamnesis, have an increased risk of its development at reception of APF inhibitors.

For newborns and babies who were exposed to pre-natal influence of APF inhibitors it is recommended to conduct careful observation for early detection of the expressed lowering of arterial pressure, oligurias, a hyperpotassemia and neurologic frustration, possible owing to reduction of the renal and brain blood-groove at a lowering of arterial pressure caused by APF inhibitors. At an oliguria maintenance of arterial pressure and renal perfusion by administration of the corresponding liquids and vasoconstrictors is necessary.

At patients with reduced function of kidneys it is necessary to reduce a single dose or to increase intervals between administrations of drug.

Before a research of functions of Berlipril® epithelial bodies it is necessary to cancel.

During treatment it is not recommended to use alcoholic nalitka since alcohol strengthens hypotensive effect of drug.

During treatment it is necessary to abstain from driving of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions since dizziness, especially after an initial dose of APF inhibitor at the patients accepting diuretic means is possible.

It is necessary to be careful when performing physical exercises at hot weather (risk of development of dehydration and excessive decrease in the ABP because of decrease in volume of the circulating blood). Before surgical intervention (including stomatology) it is necessary to warn the surgeon / anesthesiologist about use of APF inhibitors.

Side effects:

Берлиприл® in general it is well transferred and in most cases does not cause the side reactions demanding drug withdrawal.

From cardiovascular system:
the excessive lowering of arterial pressure, orthostatic collapse, is rare - a retrosternal pain, stenocardia, a myocardial infarction (are usually connected with the expressed lowering of arterial pressure), arrhythmias (atrial bradi-or tachycardia, atrial fibrillation), heartbeat, a thromboembolism of branches of a pulmonary artery, pain in heart, a syncope.

From a nervous system:
dizziness, headache, weakness, sleeplessness, alarm, confusion of consciousness, increased fatigue, drowsiness (2-3%), is very rare at use of high doses - nervousness, a depression, paresthesias.

From sense bodys:
disturbances of a vestibular mechanism, hearing disorder and sight, sonitus.

From digestive tract:
dryness in a mouth, anorexia, disiptichesky frustration (nausea, diarrhea or a lock, vomiting, pains in a stomach), intestinal impassability, pancreatitis, an abnormal liver function and a zhelchevydeleniya, hepatitis, jaundice.

From respiratory system:
unproductive dry cough, intersticial pneumonitis, bronchospasm, asthma, rhinorrhea, pharyngitis.

Allergic reactions:
skin rash, Quincke's disease of the person, extremities, lips, language, glottis and/or throat, dysphonia, polymorphic erythema, exfoliative dermatitis, Stephens-Johnson's syndrome, toxic epidermal necrolysis, pempigus, itch, small tortoiseshell, photosensitization, serositis, vasculitis, miositis, arthralgia, arthritis, stomatitis, glossitis.

From laboratory indicators:
giperkreatininemiya, increase in content of urea, increase in activity of "hepatic" transaminases, hyperbilirubinemia, hyperpotassemia, hyponatremia. Decrease in a hematocrit and a hemoglobin content, increase SOE, thrombocytopenia, a neutropenia, an agranulocytosis (at patients with autoimmune diseases), an eosinophilia are noted in certain cases.

From an urinary system:
renal failure, proteinuria.

Others:

alopecia, decrease in a libido, inflows.

Interaction with other medicines:

At co-administration of enalapril with non-steroidal anti-inflammatory drugs (NPVP) decrease in hypotensive effect of enalapril is possible; with kaliysberegayushchy diuretics (Spironolactonum, Triamterenum, amiloride) can lead to a hyperpotassemia; with lithium salts - to lithium removal delay (control of concentration of lithium in a blood plasma is shown).

Enalapril weakens effect of the drugs containing theophylline.

Hypotensive effect of enalapril diuretics, beta adrenoblockers, Methyldopum strengthen, nitrates, digidroperidinovy blockers of calcium channels, гидралазин, Prazozinum.

Immunodepressants, Allopyrinolum, cytostatics strengthen a gematotoksichnost. The drugs causing oppression of marrow increase risk of development of a neutropenia and/or agranulocytosis.

The concomitant use with febrifugal and soothing drugs can reduce efficiency of drug.

Contraindications:

Hypersensitivity to enalapril and other inhibitors of an angiotensin-converting enzyme, existence in the anamnesis of the Quincke's disease connected with treatment by APF inhibitors, porphyrias, pregnancies in the period of a lactation, aged up to 18 years (efficiency and safety are not established).

With care to apply Berlipril® at primary hyper aldosteronism, a bilateral stenosis of renal arteries, a stenosis of an artery of the only kidney, a hyperpotassemia, a state after transplantation of a kidney; an aortal stenosis, a mitral stenosis (with disturbances of a hemodynamics), an idiopathic hypertrophic subaortal stenosis, diseases of connecting fabric, coronary heart disease, cerebrovascular diseases, a diabetes mellitus, a renal failure (a proteinuria more than 1 g/days), a liver failure, at the patients keeping to a diet with restriction of salt or being on a hemodialysis at a concomitant use with immunodepressants and saluretics at elderly people (65 years are more senior).

Overdose:

Symptoms: the expressed lowering of arterial pressure up to development of a collapse, a myocardial infarction, an acute disorder of cerebral circulation or tromboembolic episodes, spasms, a stupor.

Treatment: the patient is transferred to horizontal position with a low headboard. In mild cases the gastric lavage and intake of saline solution, in more hard cases - the actions directed to stabilization of the ABP are shown: intravenous administration of normal saline solution, plasma substitutes, if necessary - administration of angiotensin II, a hemodialysis (enalaprilat removal speed - 62 ml/min.).

Storage conditions:

List B. To store at a temperature not above 25 °C. To store in the place unavailable to children. Period of validity. 3 years.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in the blister from aluminum foil. On 3 blisters together with the application instruction place in a cardboard box.