medicalmeds.eu Medicines Angiotensin-converting enzyme inhibitor (APF inhibitor). Enalapril-Darnitsa

Enalapril-Darnitsa

Препарат Эналаприл-Дарница. ЗАО "Фармацевтическая фирма "Дарница" Украина

Producer: CJSC Pharmaceutical Firm Darnitsa Ukraine

Code of automatic telephone exchange: C09AA02

Release form: Firm dosage forms. Tablets.

Indications to use: Unstable stenocardia. Acute myocardial infarction. Heart failure. Renovascular hypertensia. Idiopathic hypertensia.

General characteristics. Structure:

Active ingredient: enalapril;

1 tablet contains maleate enalapril (in terms of 100% dry matter) 10 mg; excipients: cellulose microcrystallic, potato starch, lactose monohydrate, calcium stearate.

Pharmacological properties:

Pharmacodynamics. Enalapril - inhibitor of an angiotensin-converting enzyme (APF). The enalapril metabolite - enalaprilat has pharmacological activity. Drug oppresses formation of angiotensin II and removes its vasoconstrictive action, reduces Aldosteronum level in a blood plasma, blocks disintegration of bradikinin, strengthens synthesis of prostaglandins. Has anti-hypertensive effect, reduces the general peripheric vascular resistance, reduces before - and an afterload, pressure in the right auricle and a small circle of blood circulation reduces.

Pharmacokinetics. After intake about 60% of the accepted dose are absorbed from a digestive tract. In a liver enalapril is exposed to hydrolysis therefore enalaprilat is formed that blocks action of an angiotensin-converting enzyme and formation of angiotensin P. The maximum concentration of enalapril in blood serum is reached in 1 h, enalaprilat - in 3 - 4 h after reception, duration of action-12 - 24 h. The beginning of removal of drug from plasma occurs already in 6 h, full excretion comes in 30 - 35 h. It is generally removed by kidneys, 94% of the applied enalapril are removed in the form of enalaprilat. An elimination half-life - about 11 h.
Pharmaceutical characteristics.

Main physical and chemical properties: tablets of a ploskotsilindrichesky form with a hyphen, white color.

Indications to use:

• Essential hypertensia of any stage.

• Renovascular hypertensia.

• Heart failure of any stage.

At patients with clinically expressed heart failure of Enalapril-Darnitsa apply on purpose:

• survival improvements;

• delays of progressing of heart failure;

• decrease in frequency of hospitalization concerning heart failure.
Prevention of development of clinically expressed heart failure.

At patients with asymptomatic dysfunction of a left ventricle of Enalapril-Darnitsa promotes:

• to delay of development of clinically expressed heart failure;

• to reduction of number of hospitalization concerning heart failure.
Prevention of coronary ischemia at patients with dysfunction of a left ventricle on purpose:

• reduction of frequency of development of a myocardial infarction;

• reduction of frequency of hospitalization concerning unstable stenocardia.

Route of administration and doses:

Doses are appointed by the doctor individually for each patient depending on his state.

Pill is taken inside whole, with a small amount of water, irrespective of reception

food. Drug needs to be accepted at the same time every day. It is impossible to accept

two doses at the same time.

Esseptsialny hypertensia.

The initial dose of drug for adults makes 10 - 20 mg once a day depending on

hypertensia degrees. At slight hypertensia the recommended initial dose makes 10 mg

in day. At other degrees of hypertensia the initial dose makes 20 mg once a day.

Maintenance dose — 1 tablet of 20 mg once a day. The dose should be selected individually for each patient, but it should not exceed 40 mg a day.

Renovascular hypertensia.

At adult patients of this group it is necessary to begin therapy with a low initial dose, for example, from 5 mg or less (use of other drugs containing 2,5 mg of enalapril is possible). Then the dose is selected according to need of the patient. It is possible to expect that at most of patients drug will be effective at everyday reception of 1 tablet of 20 mg. It is necessary to be careful at treatment of Enalaprilom-Darnitsa of patients who shortly before it accepted diuretics.

The accompanying treatment of arterial hypertension diuretics.

After the first reception of Enalaprila-Darnitsa there can be arterial hypotension. Such

effect the most probable at the patients receiving treatment by diuretics. In this case

drug is recommended to appoint with care as at .taky patients deficit of liquid or sodium can be observed. Treatment by diuretics should be stopped in 2 - 3 days prior to treatment of Enalaprilom-Darnitsa. If it is impossible, then it is necessary to lower an initial dose of enalapril (to 5 mg or less) to define primary influence of drug on arterial pressure. Further the dose should be selected according to need of the patient.

Cordial insufficiency / asymptomatic disfunkiiya of a left ventricle.

The initial dose makes 2,5 mg once a day; dose adjustment depends on portability

drug. At absence or after effective treatment of symptomatic hypotension

the dose needs to be increased gradually to the usual supported dose 20 mg which is accepted once or in 2 receptions.

Titration of a dose is recommended to spend each 2 or 4 weeks. The maximum daily

the dose makes 40 mg every day, distributed on several receptions.

Week the Dose in mg/day

Week 1 1-3 day: 2,5 mg/day once 4-7 day: 5 mg/day in 2 receptions

Week of 2 10 mg once or in 2 receptions

Week of 3 and 4 20 mg once or in 2 receptions

In need of use of a dose of 2,5 mg it is necessary to use drug in corresponding

to dosage.

During treatment of Enalaprilom-Darnitsa it is recommended to control function of kidneys and potassium concentration in serum.

Dosing at renal an enalapril nedostatochnosti:doza for patients from chronic

renal failure depend on clearance of creatinine; it is necessary to extend intervals between

receptions and/or to lower doses.

Clearance of creatinine Initial dose, mg/day

30-80 ml/min. 5 - 10 mg

10 - 30 ml/min. 2,5 mg

≤ 10 ml/min. 2,5 mg in days of carrying out dialysis *

* In days when dialysis is not carried out, the doctor adjusts dosing depending on

level of arterial pressure.

The medical dose for patients of advanced age has to answer a functional state

kidneys.

Features of use:

Use during pregnancy or feeding by a breast.

Do not apply.
Children.

Efficiency and safety of use of Enalaprila-Darnitsa for treatment of children are not established therefore it is not appointed to patients of this age category.

Drug needs to be accepted at the same time every day. With care use drug the patient with abnormal liver functions, to persons with autoimmune diseases.

Clinically expressed arterial hypotension.

Arterial hypotension is observed more often at the patients with heart failure of heavy degree applying high doses of loopback diuretics with a hyponatremia or renal failures. Such patients need to begin treatment of Enalaprilom-Darnitsa under observation of the doctor. At change of a dose of Enalaprila-Darnitsa and/or diuretic control has to be especially careful. It is similarly necessary to watch patients with coronary heart disease, and also with diseases of vessels of a brain at which the sharp lowering of arterial pressure can lead to a myocardial infarction or a stroke. At development of arterial hypotension of the patient it is necessary to put and if it is necessary, to enter intravenously normal saline solution. Tranzitorny arterial hypotension at reception of Enalaprila-Darnitsa is not a contraindication for treatment by drug which can be prolonged after recovery of volume of liquid and normalization of arterial pressure. At some patients with heart failure and normal or reduced arterial pressure of Enalapril-Darnitsa can reduce the level of arterial pressure in addition. Such reaction to administration of drug can be expected, and it should not be regarded as the basis for the treatment termination. When arterial hypotension becomes resistant to treatment, it is necessary to lower a dose and/or to stop treatment by diuretic and/or Enalaprilom-Darnitsa.

Aortal stenosis / hypertrophic kaudiomiopatiya.

As well as patients need to appoint all vazodilatator, APF inhibitors with care with obstruction of the leaving opening of a left ventricle.

Disturbance of a day lily of kidneys.

Some patients have an arterial gigtotenziya developing after an initiation of treatment APF inhibitors, can lead to deterioration in function of kidneys. In certain cases reported about development of an acute renal failure, usually reversible character. Patients with a renal failure can have a need for a dose decline and/or frequencies of administration of drug.

It is necessary to avoid purpose of drug to patients with a bilateral stenosis of renal arteries or a stenosis of an artery of the only kidney.

Before an initiation of treatment and during therapy it is necessary to carry out monitoring of function of kidneys. At some patients at whom diseases of kidneys to an initiation of treatment were not revealed Enalapril-Darnitsa in a combination with diuretics rendered usually slight and rapid increase of level of urea in blood and creatinine in blood serum. In such cases, perhaps, it is necessary to reduce a dose and/or to cancel diuretic and/or Enalapril-Darnitsa.

Гиперчувствительностъ / Quincke's disease.

At use of APF inhibitors, inclusive with Enalaprilom-Darnitsa, isolated cases of a Quincke's disease of the person, extremities, lips, language, a glottis and/or throat which arose during the different periods of treatment were described. In these cases it is necessary to stop immediately treatment of Enalaprilom-Darnitsa and to establish constant observation of the patient to make sure of total disappearance of symptoms. Only after this observation it is possible to stop. If hypostasis is limited to the site of the person and lips, usually special treatment is not required.

The Quincke's disease of a throat can lead to a fatal outcome. When hypostasis is localized in the site of language, a glottis or throat and can serve as the reason of obstruction of respiratory tracts, it is necessary to begin quickly the corresponding therapy which can include hypodermic administration of solution of adrenaline 1:1000 (0,3 - 0,5 ml) and/or measures for ensuring passability of respiratory tracts.

The patients having a Quincke's disease which is not connected using APF inhibitors in the anamnesis can have the increased risk of its emergence and at treatment by APF inhibitor (see also section "Contraindications").

Occasionally at the patients applying APF inhibitors during desensitization allergen from poison of Hymenoptera anaphylactoid reactions which could be menacing for life of patients developed. Similar reactions can be avoided if prior to the beginning of desensitization it is temporary to stop APF inhibitor use.

The patients who are on a hemodialysis.

At the patients who are on dialysis with use of membranes of high capacity (for example, AN 69^) and which apply at the same time APF inhibitor, in certain cases developed anaphylactoid reactions. Therefore for such patients use of dialysis membranes of other type or antihypertensive of other group is recommended.

Cough.

It was reported about developing of cough at treatment by APF inhibitors, Usually cough has unproductive, resistant character and disappears after drug withdrawal that needs to be considered at differentsionny diagnosis of cough.

Patients with a diabetes mellitus.

Due to the delay of destruction of bradikinin sensitivity of cells to insulin increases and glucose utilization increases. With a diabetes mellitus like II which use insulin or glucose-lowering drugs Enalapril-Darnitsa needs to be applied to prevention of development of a hypoglycemia in patients in smaller doses or to reconsider dosing of anti-diabetic means.

Hyperpotassemia.

Enalapril-Darnitsa interferes with potassium loss therefore at its joint therapy there is no need to use kaliysberegayushchy diuretics and drugs of potassium. In case of their use development of a hyperpotassemia, especially at patients with renal is possible

insufficiency and diabetes mellitus. Before a research of function of epithelial bodies

Enalapril-Darnitsa it is necessary to cancel.

Lactose.

As drug contains lactose, it is contraindicated to patients with a lactose intolerance.

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

During treatment of Enalaprilom-Darnitsa it is necessary to abstain from control of motor transport or work with other difficult mechanisms.

Side effects:

Disturbances from system of blood and lymphatic system:

often: anemia (including aplastic and hemolitic);

seldom: neutropenia, decrease in hemoglobin, decrease in a hematocrit, thrombocytopenia,

agranulocytosis, oppression of activity of marrow, pancytopenia, lymphadenopathy,

autoimmune diseases. Metabolic disturbances:

infrequently: hypoglycemia.

Disturbances from a nervous system and mental disorders:

often: headache, depression, dizziness;

infrequently: confusion of consciousness, drowsiness, sleeplessness, nervousness, paresthesia,

dizziness;

seldom: sleep disorder.

Disturbances from an organ of sight:

very often: the obscured sight.

Disturbances from cardiovascular system:

often: arterial hypotension (including orthostatic hypotension), a syncope, a heart attack

myocardium or stroke, breast pain, disturbance of a cordial rhythm, stenocardia,

tachycardia;

infrequently: the accelerated heartbeat;

seldom: sindty Reynaud.

Disturbances from a respiratory organs:

very often: cough;

often: asthma;

infrequently: rhinorrhea, throat inflammation, dysphonia, bronchospasm/asthma;

seldom: infiltration of lungs, rhinitis, allergic alveolitis / eosinophilic pneumonia.

Disturbances from a digestive tract:

very often: nausea;

often: diarrhea, abdominal pain, taste alteration;

infrequently: impassability of intestines, pancreatitis, vomiting, dyspepsia, a lock, anorexia, dryness in a mouth, round ulcers;

seldom: stomatitis / aphthous ulcers, glossitis. Disturbances from a liver and a gall bladder:

seldom: liver failure; hepatocellular or cholestatic hepatitis; гепатонекроз; a cholestasia, including jaundice.

Disturbances from skin and hypodermic fabrics:

often: rash, hypersensitivity / Quincke's disease;

infrequently: the strengthened potovydeleniye, an itch, urticaria, an alopecia;

seldom: polymorphic erythema, Stephens-Johnson's syndrome, exfoliative dermatitis, toksikodermalny necrolysis, pempigus, erythrosis.

It is informed on a complex of symptoms: a fever, a serositis, a vasculitis, миалгия / a miositis, arthralgia/arthritis, a positive take on antinuclear antibodies, increase SOE, an eosinophilia and a leukocytosis.

Disturbances from an urinary system:

infrequently: renal failure, renal failure, proteinuria;

seldom: oliguria.

Disturbances from a reproductive system and mammary glands:

infrequently: impotence;

seldom: gynecomastia. General disturbances:

very often: adynamy;

often: fatigue;

infrequently: muscular spasms, inflows, a ring in ears, a sensation of discomfort. Laboratory indicators:

often: a hyperpotassemia, increase in level of creatinine in blood serum;

infrequently: increase in level of urea in blood, a hyponatremia;

seldom: increase in level of enzymes of a liver, increase in bilirubin in serum.

Interaction with other medicines:

The drugs containing Cimetidinum prolong action of Enalaprila-Darnitsa. Parallel use of Enalaprila-Darnitsa and drugs containing lithium can strengthen side effects of lithium.

Combined use of Enalaprila-Darnitsa and non-steroidal anti-inflammatory drugs and analgetik can (as a result of prostaglandin synthesis braking) to lead to reduction of efficiency of Enalaprila-Darnitsa and increase in risk of a renal failure and/or heart failure.

Parallel treatment of Enalaprilom-Darnitsa and cyclosporine needs to be carried out with care in connection with a possible renal failure.

At simultaneous use of Enalaprila-Darnitsa and theophylline the theophylline elimination half-life can decrease.

Simultaneous use of Enalaprila-Darnitsa with the diuretics or other drugs reducing arterial pressure increases efficiency of these means. Combined use of Enalaprila-Darnitsa and cardiac glycosides, beta-blockers, Methyldopums, nitrates, antagonists of calcium, a gidralazin or Prazozinum is followed by abstinent synergy effect.

Simultaneous use of Enalaprila-Darnitsa and Spironolactonum, amiloride, Triamterenum or drugs of potassium can lead to a hyperpotassemia, especially at patients with a chronic renal failure.

Contraindications:

Hypersensitivity to enalapril or to other inhibitors of an angiotensin-converting enzyme, or to any component of drug. To patients with the Quincke's disease recorded in the anamnesis connected using APF inhibitors. Hereditary or idiopathic neurotic hypostasis. Bilateral renal artery stenosis; renal artery stenosis of the only kidney. Hyperpotassemia; anury. Pregnancy and period of feeding by a breast. Children's age.

Overdose:

There are limited data on overdose of drug at the person. The expressed arterial hypotension developing approximately in 6 h after administration of drug is the main signs of overdose, according to the existing data, and the renin angiotensin, and a stupor matches blockade of system. The enalaprilat levels in a blood plasma exceeding the maximum levels which are reached at reception of therapeutic doses in 100 and 200 times were registered after reception respectively 300 mg and 440 mg of enalapril. For treatment of overdose intravenous infusions of 0,9% of solution of sodium of chloride are recommended. At an opportunity angiotensin II infusion can be useful. If drug was accepted recently, the gastric lavage is recommended. Enalaprilat can be removed from system blood circulation by means of a hemodialysis (see. "Features of use, the patients who are on a hemodialysis").