Эналаприл-Акри®

General characteristics. Structure:

Active ingredients: 0,005 g or 0,01 g of enalapril.

Excipients: sugar milk, potato starch, talc, magnesium stearate.

Pharmacological properties:

Pharmacodynamics. ^{Эналаприл-Акри®} - anti-hypertensive drug, 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, systolic and diastolic arterial pressure, post-and preload of a myocardium goes down.

Expands arteries more than veins, at the same time reflex increase in heart rate is not noted. Reduces degradation of bradikinin, increases prostaglandin synthesis. The hypotensive effect is more expressed at the high level of a renin of a blood plasma, than normal or its reduced level. The lowering of arterial pressure in therapeutic limits does not exert impact on cerebral circulation, the blood stream in vessels of a brain is supported at the sufficient level against the background of reduced 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 resistant type decreases, prevents progressing of 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. Enalapril is "pro-medicine": as a result of its hydrolysis enalaprilat which inhibits APF is formed. Time of approach of hypotensive effect at intake - 1 hour, reaches a maximum in 4-6 hours and remains till 24 o'clock.

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 use - 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 hour, enalaprilat - in 3-4 hours.

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 hours. Enalapril generally through kidneys of 60% (20% in the form of enalapril and 40% in the form of enalaprilat), through intestines - 33% is removed (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:

^{Эналаприл-Акри®} appoint at various forms of arterial hypertension, including renovascular hypertensia. Drug is also effective at chronic heart failure (as a part of a combination therapy).

Route of administration and doses:

Эналаприл-Акри® appoint inside irrespective of meal time. At monotherapy of arterial hypertension an initial dose - 5 mg once a day. 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 within 2 hours and in addition 1 hour, is not stabilized arterial pressure yet. If necessary and rather good tolerance, it is possible to increase a dose to 40 mg a day for 1-2 receptions. In 2-3 weeks pass to the maintenance dose equal 10-40 mg a day divided into 1-2 receptions. At moderate hypertensia the average daily dose makes about 10 mg. The maximum daily dose - 40 mg.

If it is necessary to appoint Enalapril-Akri® to the patient who accepts diuretics, treatment by diuretics needs to be stopped in 2-3 days prior to use of Enalaprila-Akri®. If it is impossible, then the initial dose of Enalaprila-Akri® 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 at increase in concentration of creatinine in blood serum more than 0,14 mmol/l are appointed by Enalapril-Akri® in an initial dose of 2,5 mg of 1 times a day.

At renovascular hypertensia an initial dose - 2,5-5 mg/days. The maximum daily dose makes 20 mg.

At chronic heart failure an initial dose of Enalaprila-Akri® - 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 in dependence on sizes 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/days with a dose. Selection of a dose has to be carried out within 2-4 weeks or if necessary and opportunities to shorter terms. An average maintenance dose - 5-20 mg/days for 1-2 receptions.

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

At a chronic renal failure cumulation of enalapril comes at decrease in filtering less than 10 ml/min. At the clearance of creatinine (CC) of 80-30 ml/min. the dose of enalapril has to make 5-10 mg/days, at decrease in 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 lowering of arterial pressure the dose of Enalaprila-Akri® 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 purpose of drug 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 arterial pressure, 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 rise in arterial pressure). Patients with the indication 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 underwent 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 function ^{of Enalapril-Akri® epithelial bodies} it is necessary to cancel. During treatment it is not recommended to take alcoholic beverages as alcohol strengthens hypotensive effect of drug. During treatment it is necessary to refrain from driving of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions as 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 lowering of arterial pressure because of decrease in volume of the circulating blood). Before surgical intervention (including stomatology) it is necessary to warn the surgeon/anaesthesiologist about use of APF inhibitors.

Side effects:

From cardiovascular system: the excessive lowering of arterial pressure, an 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, a headache, weakness, insomnia, alarm, confusion of consciousness, 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, dispeptic 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 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.
Other side effects: alopecia, decrease in a libido, inflows.

Interaction with other medicines:

At co-administration ^{of Enalaprila-Akri®} with non-steroidal anti-inflammatory drugs decrease in hypotensive effect is possible. Use of drug together with kaliysberegayushchy diuretics (Spironolactonum, Triamterenum, amiloride) can lead to a hyperpotassemia, with lithium salts - to delay of removal of lithium in a blood plasma (control of concentration of lithium in a blood plasma is shown).

The concomitant use ^{of Enalaprila-Akri®} with febrifugal and soothing drugs can reduce efficiency of enalapril.

Enalapril weakens effect of the medicines containing theophylline. Hypotensive effect of enalapril diuretics, beta adrenoblockers, Methyldopum strengthen, nitrates, blockers of "slow" 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 up to death.

Contraindications:

^{Эналаприл-Акри®} it is contraindicated at hypersensitivity to enalapril and other inhibitors of the angiotensin-converting enzyme (ACE), in the presence 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.

With care it is necessary to apply ^{Enalapril-Akri®} at primary 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, general 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 are shown. In more hard cases the actions directed to stabilization of arterial pressure are recommended: intravenous administration of normal saline solution, plasma substitutes, and if necessary - angiotensin II, a hemodialysis (speed of removal of enalapril averages 62 ml/min.).

Storage conditions:

List B. At a temperature not above 25 °C, in the dry, protected from light place unavailable to children. Not to apply after the expiry date specified on packaging. A period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

Tablets on 0,005 g or 0,01 g. On 10 tablets in a blister strip packaging. On 2, 3 or 10 blister strip packagings in a pack.