Эналозид® 12,5

General characteristics. Structure:

Active ingredients: enalapril; Hydrochlorthiazidum;

1 tablet contains substance in terms of 100%: maleate enalapril - 10 mg, Hydrochlorthiazidum - 12,5 mg;

excipients: lactoses monohydrate; potato starch; povidone; calcium stearate.

Pharmacological properties:

Pharmacodynamics. Эналозид® 12,5 treats group of the combined anti-hypertensive means. Enalapril the maleate which is a part of drug is inhibitor of an angiotensin-converting enzyme (APF) which turns angiotensin I into angiotensin ІІ. Drug causes expansion of peripheral arteries, decrease in the general peripheric vascular resistance, reduction of preload and afterload of heart, decrease in resistance in vessels of kidneys and reduction of allocation of Aldosteronum. Hydrochlorthiazidum causes moderate diuretic effect, leads to reduction of volume of the circulating blood, reduces the maintenance of ions of sodium in walls of vessels and reduces their sensitivity to vasoconstrictive influences. At simultaneous use of enalapril of a maleate and Hydrochlorthiazidum their anti-hypertensive effect mutually amplifies.

Pharmacokinetics. After intake from digestive tract about 60% of enalapril and about 60-75% of Hydrochlorthiazidum are absorbed. Enalapril is exposed to hydrolysis with formation of the APF active inhibitor - enalaprilat which maximum concentration in blood is observed in 3-4 hours. The diuretic effect of Hydrochlorthiazidum occurs in 2 hours, reaches a maximum in 3-4 hours and lasts till 24 o'clock. Drug is emitted preferential with kidneys. The elimination half-life of enalaprilat makes 11 hours, and Hydrochlorthiazidum – till 10 o'clock. Patients with a severe form of a renal failure have elimination half-lives of enalaprilat and Hydrochlorthiazidum increase.

Pharmaceutical characteristics.

Main physical and chemical properties: tablets of color, white or white with a creamy shade, with a flat surface, a facet and risky, or without risks.

Indications to use:

Treatment of arterial hypertension at patients for whom the combination therapy is considered more reasonable.

Route of administration and doses:

At arterial hypertension. Initial dose of drug 1 tablet (12,5 mg) 1 times/days. If the desired effect is absent, then the daily dose is increased to 2 tablets (25 mg) of 1 times a day. The maximum dose - 2 tablets (on 25 mg) in days.

At a renal failure. For patients with an impaired renal function, at the moderated or expressed renal failure (level of clearance of creatinine of 30 ml/min. and below) tiazida can be insufficiently effective.

If creatinine level in the range from> 30 to <80 ml/min. Эналозид® 12,5 has to be applied only after preliminary selection of a dose of each of components.

At a moderate renal failure the recommended enalapril dose a maleate which is accepted separately makes from 5 to 10 mg.

If the patient already receives diuretics.

If the patient already receives diuretics, then it is recommended to cancel treatment or to reduce a dose of diuretics, in 2-3 days prior to therapy Эналозидом® 12,5, in order to avoid sharp decrease AP (arterial pressure). Symptomatic arterial hypotension can arise at the beginning of therapy Эналозидом® 12,5 and is more often observed at patients in whom the previous therapy by diuretics caused disturbance of water and electrolytic balance.

Features of use:

At some patients development of symptomatic arterial hypotension is possible, as well as at use of other means of anti-hypertensive therapy. Patients have to be inspected for the purpose of identification of clinical signs of disturbance of water and electrolytic balance, such as hyponatremia, a lack of liquid, a gipokhloremichesky alkalosis, a hypomagnesiemia or a hypopotassemia which can arise owing to episodes of diarrhea or vomiting. It is necessary to determine periodically at such patients the level of electrolytes in serum through the corresponding periods.

The excessive lowering of arterial pressure can lead to a myocardial infarction or a stroke at patients with coronary heart disease or cerebrovascular diseases.

At development of arterial hypotension of the patient it is necessary to lay, raise the lower extremities, and if necessary to enter intravenously normal saline solution. Passing arterial hypotension at appointment Эналозида® 12,5 is not a contraindication for further therapy. Therapy can be recovered or in the reduced doses, or with use of each component of drug separately, after normalization of arterial pressure and volume of the circulating liquid.

APF inhibitors (as well as all other vasodilators) have to be applied with care at patients with obstruction of outflow tracts of blood from a left ventricle.

At the moderated or expressed renal failure (when the level of clearance of creatinine of 30 ml/min. and below) tiazida can be insufficiently effective diuretics. At clearance of creatinine <80 ml/min. of Enalozid® should be applied only after the previous selection of a dose of each of components

At therapy by enalapril in combination with Diuretinum some patients, without any symptoms of a disease of kidneys to an initiation of treatment, had a slight and passing increase of level of urea in blood and creatinine in serum. In such cases treatment Эналозидом® 12,5 needs to be stopped; with possible further resuming of therapy in the reduced doses or purpose of each component of drug separately.

At treatment by APF inhibitors of patients with a bilateral stenosis of renal arteries or with a stenosis of an artery of the only kidney observed increase in content of urea in blood and creatinine in serum. These changes were reversible and were normalized after the treatment termination.

Tiazida have to be applied with care at patients with dysfunction or with the progressing liver diseases as even minor changes of water and electrolytic balance can cause a hepatic coma.

During big surgical interventions or during anesthesia using means which cause arterial hypotension enalaprilat blocks formation of angiotensin II for the second time before compensatory release of a renin. If at the same time arterial hypotension which is explained by the similar mechanism develops, it can be adjusted increase in volume of liquid.

Tiazida are capable:
to change tolerance to glucose (correction of doses of anti-diabetic drugs, including insulin is possible);
to reduce calcium excretion with urine which leads to the insignificant and reversible growth of level of calcium in serum (the expressed hypercalcemia can be a sign of the hidden hyperparathyreosis). Before carrying out a research of functions of epithelial bodies reception of tiazid has to be stopped;
to increase the level of cholesterol and triglycerides that too can be connected with therapy by diuretics of a tiazidovy row, but at a dose of Hydrochlorthiazidum of 12,5 mg similar effects or were not observed at all, or were insignificant;
can cause a hyperuricemia and/or gout in some patients, but enalapril can increase the level of uric acid in urine and by that to reduce giperurikemichesky effect of a hydrochlorothiazide.

During treatment by APF inhibitors, including enalapril a maleate, separate cases of a Quincke's disease of the person, extremities, lips, language, a glottis and/or throat were described. In such cases it is necessary to stop immediately treatment by drug and to establish careful observation of a condition of the patient, for the purpose of control of clinical symptoms. Only at their disappearance medical observation can be stopped. If hypostasis extends to the site of the person and lips, therapy by antihistaminic drugs in these cases provides a favorable effect.

Angionevrotichny hypostasis which is followed by throat hypostasis can lead to the fatal end. At localization of hypostasis in the field of language, the glottis or a throat that can lead to obstruction of respiratory tracts, should enter immediately subcutaneously adrenaline 1:1000 solution (0,3-0,5 ml) and to carry out other relevant medical activities.

Patients in whose anamnesis there were cases of a Quincke's disease which are not connected with reception of APF inhibitors are more inclined to emergence of a Quincke's disease against the background of therapy by APF inhibitors.

Patients against the background of therapy have tiazidam, allergic reactions can arise irrespective of existence in the anamnesis of allergic states or bronchial asthma. Patients who received tiazida have data on a recurrence or deterioration in course of a system lupus erythematosus.

Occasionally at patients who receive APF inhibitors heavy anaphylactoid reactions developed during desensitization allergen from poison of Hymenoptera. Similar reactions can be avoided if by the beginning of carrying out desensitization it is temporary to stop reception of APF inhibitors.

Anaphylactoid reactions were observed at patients who were on dialysis with use of membranes with a high capacity (such as AN 69®), and received at the same time treatment by APF inhibitors. At these patients it is necessary to use dialysis membranes of other type or hypotensive drugs of other classes.

Cough cases against the background of therapy were observed by APF inhibitors. Usually cough has unproductive, constant character and stops after drug withdrawal.

Efficiency and portability of enalapril of a maleate and Hydrochlorthiazidum at simultaneous use are similar to effects at elderly and young patients.

Lactose therefore this drug is not recommended to be accepted to patients with inborn intolerance of a galactose, with deficit of lactase or disturbance of absorption of glucose or a galactose is a part of the tablets Эналозида® 12,5.

It is not necessary to take alcohol during treatment Эналозидом® 12,5.

Ability to influence speed of response at control of motor transport or work with other mechanisms. With care to apply in operating time to drivers of vehicles and persons whose profession is connected with the increased concentration of attention (perhaps considerable decrease in the ABP and dizziness, especially in an initiation of treatment).

Side effects:

Treatment Еналозидом® 12,5, as a rule, is well transferred.

Side effects most of which often met: dizziness and the increased fatigue, were insignificant and disappeared at a dose decline and occasionally demanded drug withdrawal.

Side effects which meet frequency - 1-2% of cases: orthostatic effects, including arterial hypotension, a headache, spasms, nausea, an adynamy, cough and impotence.

Side effects which seldom met:

from cardiovascular system: dizziness; not orthostatic hypotension; strong heartbeat; tachycardia; arrhythmia; stethalgia.

From digestive tract: pancreatitis; diarrhea; vomiting; dyspepsia; abdominal pain; meteorism; lock; sialadenitis.

From a nervous system / mentality: sleeplessness; drowsiness; paresthesias; dizziness, nervousness; syncope.

From a respiratory organs: asthma.

Dermatological reactions: multiformny erythema (Stephens-Johnson's syndrome); rash; photosensitization, itch; the increased perspiration, and other dermatological manifestations.

From system of a hemopoiesis: positive test for antinuclear antibodies (ANA), increase in the blood sedimentation rate (BSR), eosinophilia and leukocytosis.

Allergic reactions: hypersensitivity / ангионевротичний swelled. The Angionevrotichny face edema, extremities, lips, language, a glottis and/or a throat met occasionally (see the section "Features of Use").

Datas of laboratory: the hyperglycemia, a hyperuricemia and hypo - or a hyperpotassemia, decrease in indicators of hemoglobin and a hematocrit, increase in level of urea in blood, serumal creatinine, increase in level of liver enzymes and/or bilirubin in serum, a hypoglycemia at patients who accept antihyperglycemic means were seldom noted.

Others: renal dysfunction; renal failure; decrease in a libido; dryness in a mouth; gout; sonitus; arthralgia, fever, serositis, vasculitis, mialgiya, miositis, arthralgia / arthritis, syndrome of disturbance of secretion of antidiuretic hormone.

At appointment Эналозида® 12,5 clinically important changes of laboratory indicators were observed seldom. These indicators were usually normalized after the termination of therapy Эналозидом® 12,5.

Interaction with other medicines:

At a concomitant use of other anti-hypertensive means (tricyclic antidepressants, fenotiazid, ethanol) anti-hypertensive action Эналозида® 12,5 amplifies.

Analgetics antipyretics, non-steroidal anti-inflammatory drugs, the increased content of salt in food, the concomitant use of Colestyraminum or a kolestipol weakens action Эналозида® 12,5.

Under the influence of Hydrochlorthiazidum toxic action of high doses of salicylates on the central nervous system amplifies.

Simultaneous use Эналозида® 12,5 and drugs of lithium can cause intoxication lithium due to decrease in its clearance.

Simultaneous use of kaliysberegayushchy diuretics (Spironolactonum, amiloride, Triamterenum) or additional reception of potassium can lead to a hyperpotassemia.

The concomitant use of Allopyrinolum, tsitostatik, immunodepressants or system corticosteroids can cause a leukopenia, anemia or a pancytopenia; together with cyclosporine can lead to development of a renal failure.

The concomitant use of sulfonamides or hypoglycemic means, derivatives of sulphonylurea can cause allergic reactions (the cross allergy is possible).

With care it is necessary to appoint at the same time foxglove drugs as its toxicity can increase because of a hypovolemia, a hypopotassemia and a hypomagnesiemia.

The concomitant use of corticosteroids increases risk of development of a hypopotassemia.

The risk of development of arterial hypotension increases when carrying out the general anesthesia or at simultaneous use of not depolarizing muscle relaxants, for example tubocurarine.

With care Еналозид® 12,5 patients who receive orally hypoglycemic means or insulin as Hydrochlorthiazidum weakens effect of these drugs need to appoint, and enalapril can increase it, at the same time there can be a need for change of doses of hypoglycemic means. During treatment it is periodically necessary to control concentration of electrolytes, urea, glucose, creatinine, activity of hepatic transaminases in blood serum, blood indicators, and also availability of protein in urine.

Contraindications:

The available disturbances of functions of a liver;
state after transplantation of kidneys, an anury, a bilateral renal artery stenosis, a renal artery stenosis of the only kidney;
the expressed renal failures (the clearance of creatinine (CC) is lower than 0,5 ml/sec. or serumal creatinine more than 265 µmol/l or respectively – more than 3 mg/dl);
Quincke's disease in the anamnesis;
porphyria;
primary hyper aldosteronism;
severe forms of gout and diabetes mellitus;
pregnancy (especially ІІ and ІІІ trimesters);
feeding period breast;
hypersensitivity to drug components;
hypersensitivity to streptocides.

Because of the increased risk of development of anaphylactic reactions Эналозид® 12,5 it is not necessary to appoint the patient who is on a hemodialysis with use of polyacrylonitrile membranes, before use of drugs of a dextran or performing specific desensitization to aspen or to apitoxin.

Overdose:

Overdose symptoms: arterial hypotension, nausea, weakness, dizziness against the background of disturbances of electrolytic balance. In case of accidental overdose it is necessary to make a gastric lavage if drug was accepted recently; and also correction of water and electrolytic balance and arterial hypotension by means of the standard actions. The patient has to be under careful medical observation, therapy of Enalozidom®12,5 has to be stopped. Treatment of overdose of Enalozidom®12,5 symptomatic and supporting.

Enalapril maleate.

According to the existing data, the most expressed enalapril overdose signs – arterial hypotension, owing to blockade of system a renin angiotensin which begin approximately in 6 hours after administration of drug, and a stupor. Enalaprilat levels in a blood plasma which exceed the maximum levels in 100 and 200 times were registered after reception respectively 300 mg and 440 mg of enalapril a maleate.

For treatment of overdose recommend intravenous injection of normal saline solution. By means of a hemodialysis enalaprilat can be removed from a system blood-groove.

Hydrochlorthiazidum.

The symptomatology caused by loss of electrolytes (a hypopotassemia, a hypochloraemia, a hyponatremia) and dehydration through the raised diuresis is most often observed. If earlier digitalis drugs were appointed, the hypopotassemia can strengthen displays of arrhythmias. Symptomatic treatment.

Use during pregnancy or feeding by a breast. Эналозид® 12,5 it is contraindicated during pregnancy and during feeding by a breast. At the first signs of pregnancy it is necessary to stop administration of drug urgently. Purpose of APF inhibitors in І and ІІІ trimesters of pregnancy can cause a disease or death of a fruit (newborn). If drug is appointed during pregnancy, the patient needs to be warned about risk for a fruit. Seldom or never, when purpose of drug at pregnancy is considered necessary, it is necessary to conduct periodic ultrasonic examinations for assessment of a condition of a fruit, and also intraamniotichesky space.

In need of purpose of drug in the period of a lactation it is necessary to refuse feeding by a breast

Children. Safety of use of drug at treatment of children (age up to 18 years) is not established therefore appointment it is not recommended.

Storage conditions:

Period of validity 2 years. Not to use drug after the termination of the period of validity specified on packaging. To store in the unavailable to children, dry, 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 2 blisters in a pack.