Enalapril-Acry - instructions for use, dose, side effects, contraindications

active substance: enalapril maleate in terms of 100% substance - 5 mg or 10 mg; auxiliary substances: lactose monohydrate - 132.4 mg or 162.1 mg; potato starch - 28.35 mg or 48.7 mg; talc - 2.55 mg or 6.9 mg; magnesium stearate - 1.7 mg or 2.3 mg respectively.

Description:tablets from white to white with a yellowish shade of color, flat-cylindrical, with a bevel.

Pharmacotherapeutic group:angiotensin-converting enzyme (ACE) inhibitor

ATX: & nbsp

C.09.A.A.02 Enalapril

Pharmacodynamics:

Enalapril is an antihypertensive drug whose mechanism of action is associated with a decrease in the formation of angiotensin II from angiotensin I, a decrease in its content leads to a direct decrease in the release of aldosterone. This reduces the overall peripheral vascular resistance, systolic and diastolic blood pressure (BP), post-and preload on the myocardium. Expands arteries more than veins, with a reflex increase in heart rate (heart rate) is not noted. Reduces the degradation of bradykinin. The antihypertensive effect is more pronounced with high renin activity of blood plasma than normal or reduced its activity.Decrease in blood pressure within the therapeutic limits does not affect cerebral circulation, blood flow in the vessels of the brain is maintained at a sufficient level, against a background of low blood pressure. Strengthens coronary and renal blood flow.

With long-term use, myocardial hypertrophy of the left ventricle and myocytes of the walls of arteries of resistive type decrease, prevents the progression of heart failure and slows down the development of dilatation of the left ventricle. Improves the blood supply of the ischemic myocardium.

Has some diuretic effect. It reduces intra-cerebral hypertension, slowing the development of glomerulosclerosis and the risk of chronic renal failure (CRF).

Enalapril is a "prodrug": as a result of its hydrolysis, a enalaprilate, which inhibits the angiotensin-converting enzyme (ACE). The time of onset of antihypertensive effect with ingestion is 1 hour, it reaches a maximum after 4-6 hours and lasts up to 24 hours. Some patients need therapy for several weeks to achieve optimal blood pressure.In chronic heart failure, a noticeable clinical effect is observed with long-term treatment - 6 months or more.

Pharmacokinetics:

After ingestion, absorption is 60%. Eating does not affect the absorption of enalapril. Enalapril up to 50% binds to blood plasma proteins. Enalapril is rapidly metabolized in the liver to form an active metabolite of enalaprilat, which is a more active ACE inhibitor than enalapril. Bioavailability of the drug - 40%. The maximum concentration of enalapril in the blood plasma is achieved after 1 hour, enalaprilata - after 3-4 hours. Enalaprilat easily passes through the histohematological barriers, excluding the blood-brain barrier, a small amount penetrates the placenta and into the breast milk.

The half-life of enalaprilata is about 11 hours. enalapril mainly kidneys 60% (20% in the form of enalapril and 40% in the form of enalaprilata), through the intestine - 33% (6% in the form of enalapril and 27% in the form of enalaprilate).

It is removed during hemodialysis (rate 62 ml / min) and peritoneal dialysis.

Indications:

- arterial hypertension;

- chronic heart failure (as part of combination therapy);

- prevention of the development of clinically significant heart failure in patients with asymptomatic dysfunction of the left ventricle (as part of combination therapy).

Contraindications:

Hypersensitivity to enalapril, other components of the drug and other ACE inhibitors, history of angioedema, associated with treatment with ACE inhibitors, and hereditary or idiopathic angioedema, porphyria, pregnancy, lactation, age under 18 years (efficacy and safety not established ), lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Carefully:

Primary hyperaldosteronism, bilateral stenosis of the renal arteries, stenosis of the single kidney artery, hyperkalemia, condition after kidney transplantation, aortic stenosis, mitral stenosis (with hemodynamic disorders), idiopathic hypertrophic subaortic stenosis, systemic connective tissue diseases, ischemic heart disease, cerebrovascular diseases, diabetes mellitus , renal failure (proteinuria more than 1 g / day), liver failure, patients,concomitant intake with immunosuppressants and saluretic drugs, elderly patients (over 65 years of age), oppression of bone marrow hematopoiesis, conditions accompanied by a decrease in the volume of circulating blood (including diarrhea and vomiting).

Pregnancy and lactation:

During pregnancy and lactation, the drug can not be used. If pregnancy occurs during the period of treatment with the drug Enalapril-Acry®, you should inform the doctor as soon as possible. He will prescribe another antihypertensive treatment.

Dosing and Administration:

Take inside regardless of the time of eating, squeezed with enough liquid.

Arterial hypertension

With monotherapy of arterial hypertension, the initial dose is 5 to 20 mg once a day, depending on the severity of the arterial hypertension. With mild hypertension, the recommended dose is 5-10 mg. At other degrees of severity of arterial hypertension the initial dose is 20 mg once a day. The maintenance dose is 20 mg once a day. Dosage is selected individually for each patient, but should not exceed 40 mg per day.

The maximum daily dose is 40 mg in 1-2 divided doses.

To ensure the following dosing, it is possible to use enalapril in other doses of 1.25 mg and 2.5 mg.

If Enalapril-Acry® is given to patients who are concurrently receiving diuretics, diuretic treatment should be discontinued 2-3 days before the drug is started.

Patients with hyponatremia (concentration of sodium ions in the blood serum of less than 130 mmol / l) or with an increase in serum creatinine concentration greater than 0.14 mmol / l are prescribed in an initial dose of 2.5 mg once a day.

With Renovascular hypertension, the initial dose is 2.5-5 mg / day. The maximum daily dose is 20 mg.

Chronic heart failure (as part of combination therapy)

In chronic heart failure, the initial dose is 2.5 mg once, then the dose is increased by 2.5-5 mg every 3-4 days according to the clinical response to the maximum tolerated dose (depending on blood pressure), but not more than 40 mg / day once or in 2 divided doses. In patients with low systolic blood pressure (less than 110 mm Hg), therapy should be started at a dose of 1.25 mg / day. The dose should be selected within 2-

2 weeks or, if necessary and possible, in a shorter period.

The average maintenance dose is 5-20 mg / day for 1-2 doses.

In elderly people, more pronounced antihypertensive effect and lengthening of the drug's action time are more frequent, which is associated with a decrease in the rate of excretion of the drug, therefore the recommended initial dose for elderly patients is 1.25 mg / day. Prevention of the development of clinically significant heart failure in patients with asymptomatic left ventricular dysfunction (as part of combination therapy).

With asymptomatic violation of the function of the left ventricle - 2.5 mg 2 times a day. The dose is selected taking into account the tolerability up to 20 mg / day, divided into 2 doses.

When chronic renal failure The cumulation of enalapril occurs with a decrease in filtration of less than 10 ml / min. When the creatinine clearance is 80-30 ml / min, the dose of the drug should be 5-10 mg / day, with a decrease in IC to 30-10 ml / min - 2.5 mg / day, with a CC less than 10 ml / min - 1,25-2,5 mg / day only on dialysis days.

The duration of treatment depends on the effectiveness of therapy. With too pronounced decrease in blood pressure, the dose of the drug is gradually reduced.

The drug is used in both monotherapy and in combination with other antihypertensive drugs.

Side effects:

The frequency is classified according to the headings, depending on the occurrence of the case: very often (> 1/10), often (<1 / 10-> 1/100), infrequently (<1 / 100-> 1/1000), rarely (<1 / 1000-> 1/10000), very rarely (<1/10000).

Violations from the blood and lymphatic system: infrequently - anemia (including aplastic and hemolytic anemia), rarely - neutropenia, a decrease in hemoglobin and hematocrit, thrombocytopenia, agranulocytosis, oppression of bone marrow function, pancytopenia, enlarged lymph nodes, autoimmune diseases.

Metabolic and nutritional disorders: infrequently - hypoglycemia.

From the central nervous system: often - headache, depression; infrequently - confusion, drowsiness, insomnia, increased excitability, paresthesia, dizziness; rarely - a change in the nature of dreams, sleep disturbances.

From the side of the organ of vision: very often - a violation of accommodation.

From the side of the cardiovascular system: very often - dizziness; often marked decrease in blood pressure, syncope, myocardial infarction or cerebral stroke, chest pain, heart rhythm disturbances, angina pectoris, tachycardia; infrequently: orthostatic hypotension, fainting, palpitations; rarely - Raynaud's syndrome.

From the respiratory system: very often - cough; often - dyspnoea; infrequently - rhinorrhea, sore throat and hoarseness, bronchospasm / bronchial asthma; rarely - pulmonary infiltrates, rhinitis, interstitial alveolitis / eosinophilic pneumonia.

From the digestive system: very often - nausea; often - diarrhea, abdominal pain, change in taste perception; infrequent - intestinal obstruction, ileitis, pancreatitis, vomiting, indigestion, constipation, lack of appetite, irritation of the stomach, dryness of the oral mucosa, peptic ulcer; rarely - stomatitis / aphthous ulcers, glossitis; very rarely - intestinal angioedema of the intestine.

From the liver and bile excretory system: rarely - hepatic insufficiency, hepatitis - hepatocellular or cholestatic, including hepatic necrosis, cholestasis (including jaundice).

From the side of the urinary system: rarely acute renal failure. Allergic reactions: often - skin rash, hypersensitivity reactions / angioedema (reported angioedema with involvement of the face, limbs, lips, tongue, vocal folds and / or larynx); infrequently - a skin itch,hives; rarely - erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, pemphigus, erythroderma.

A symptom complex has been reported that may be accompanied by some and / or all of the following side effects: fever, serositis, vasculitis, myalgia / myositis, arthralgia / arthritis, an increase in the titer of antinuclear antibodies (ANA), an increase in the rate of erythrocyte sedimentation, eosinophilia, and leukocytosis. Skin rashes, photosensitivity reactions or other skin manifestations may occur.

From the skin and subcutaneous fat: infrequently - alopecia. Symptomocomplex, which includes facial flushing, nausea, vomiting and arterial hypotension, is described in rare cases with the joint use of gold preparations for intravenous administration (sodium aurotomy malate) and ACE inhibitors (enalapril).

From the side of the urinary system: infrequently - impaired renal function, renal failure, proteinuria; rarely - oliguria.

On the part of the reproductive system and mammary glands: infrequently - impotence; rarely - gynecomastia.

Violations of a general nature: very often - asthenia; often fatigue; infrequently - muscle cramps, redness of the skin of the face, noise in the ears, discomfort, fever, lymphadenopathy, increased sweating.

Laboratory indicators: often hyperkalemia, increased serum creatinine concentration; infrequently - increased serum urea concentration, hypo-sodiumemia; rarely - increased activity of "liver" transaminases, hyperbilirubinemia, hyperuricemia.

Overdose:

symptoms: a marked decrease in blood pressure up to the development of collapse, myocardial infarction, acute impairment of cerebral circulation or thromboembolic complications; convulsions, stupor.

Treatment: the patient is transferred to a horizontal position with a low headboard. In mild cases showing gastric lavage and ingestion of activated charcoal.

In more severe cases, measures aimed at stabilizing blood pressure are recommended: intravenous administration of 0.9% sodium chloride solution, plasma substitutes, and if necessary - angiotensin II, hemodialysis (enalapril removal rate averages 62 ml / min).

Interaction:

With the concurrent use of Enalapril-Acry® with non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2 (COX-2), an antihypertensive effect may decrease; with potassium-sparing diuretics (spironolactone, triamterene, amiloride) can lead to hyperkalemia; with lithium salts - to slowing the excretion of lithium in the blood plasma (control of the concentration of lithium in blood plasma is shown).

In some patients with impaired renal function and host NSAIDs, including COX-2 inhibitors, concomitant use of ACE inhibitors may lead to further impairment of renal function. These changes are reversible.

Simultaneous administration of the drug with NSAIDs may decrease the effectiveness of the drug. Enalapril weakens the effect of medicines containing theophylline. The antihypertensive effect of enalapril is enhanced by diuretics, beta-blockers, methyldopa, nitrates, blockers of "slow" calcium channels, hydralazine, prazozin. Immunosuppressants, allopurinol, cytotoxic drugs increase hematotoxicity. Drugs that cause bone marrow depression increase the risk of developing neutropenia and / or agranulocytosis up to death.

The combined use of ACE inhibitors and hypoglycemic agents (insulin, hypoglycemic agents for oral administration) can enhance the hypoglycemic effect of the latter with the risk of developing hypoglycemia. This is most often observed during the first weeks of joint use, as well as in patients with renal insufficiency.

In patients with diabetes, who take hypoglycemic agents for ingestion and insulin, blood glucose control is necessary, especially during the first month of joint use with ACE inhibitors.

Symptomocomplex, which includes facial flushing, nausea, vomiting and arterial hypotension, is described in rare cases with the joint use of gold preparations for intravenous administration (sodium aurotomy malate) and ACE inhibitors (enalapril).

Special instructions:

Arterial hypotension

In case of arterial hypotension, it is necessary to place the patient on the back with a low head and if necessary adjust the volume of circulating blood by infusing a solution of 0.9% sodium chloride. Arterial hypotension, which occurred after taking the first dose, is not a contraindication for further treatment.Require caution in patients with coronary heart disease, severe cerebrovascular diseases, aortic stenosis and idiopathic hypertrophic subaortic subaortal stenosis interfering outflow of blood from the left ventricle, severe atherosclerosis in elderly patients due to the risk of hypotension and deterioration of blood supply to the heart, brain and kidneys

Potassium-sparing diuretics and potassium preparations

The combined use of drugs and enalapril Akri®-sparing diuretics, and potassium-containing preparations and potassium salt substitutes is not recommended.

Hemodialysis

Patients receiving ACE inhibitors during hemodialysis using vysokoprotochnyh membranes (e.g., AN69®) anafilaktodnye reactions were noted. Therefore, it is desirable to use a different type of membrane or to use an antihypertensive drug of another pharmacotherapeutic group.

Stenosis of the aortic and / or mitral valve / hypertrophic obstructive cardiomyopathy (GOKMP)

Like all other vasodilators,ACE inhibitors should be used with extreme caution-Akri® enalapril on patients with obstruction of the left ventricular outflow tract and avoid their use in case of cardiogenic shock and hemodynamically significant obstruction of the left ventricular outflow tract.

Violations of the water-electrolyte balance

It is necessary to regularly monitor the serum concentration of electrolytes during the treatment period to identify possible imbalances and timely take the necessary measures. Determination of the serum concentration of electrolytes is mandatory for patients with prolonged diarrhea, vomiting.

Patients taking enalapril drug-Akri® must detect signs of fluid and electrolyte balance, such as dryness of the oral mucosa, thirst, weakness, drowsiness, irritability, myalgia and cramps (mainly the gastrocnemius muscle), lower blood pressure, tachycardia , oliguria and gastrointestinal disorders (nausea, vomiting).

Allergic reactions / angioedema

When an angioedema develops in the face, it is usually sufficient to discontinue therapy and prescribe antihistamines to the patient.Angioedema, edema of the tongue, throat or larynx can be lethal. With angioedema, swelling of the tongue, throat or larynx, which can lead to airway obstruction, you must immediately enter epinephrine (0.3-0.5 ml epinephrine (adrenaline) solution subcutaneously in a ratio of 1: 1000) and maintain airway patency (intubation or tracheostomy).

Among patients of the Negroid race receiving ACE inhibitor therapy, the incidence of angioedema is higher than among patients of other race.

Patients with a history of angioedema not associated with ACE inhibitors have an increased risk of developing angioedema due to the administration of any ACE inhibitor.

Due to the increased risk of anaphylactic reactions, the Enalapril-Acry® drug should not be administered to patients on hemodialysis using high-density polyacrylonitrile membranes (AN69®), hypersensitivity to low-density lipoproteins with dextran sulfate and immediately before the procedure of desensitization by the venom of Hymenoptera.

Surgical interventions / general anesthesia

Before surgery (including dentistry), it is necessary to alert the surgeon to the anesthesia specialist about the use of ACE inhibitors.

During surgical interventions or general anesthesia with the use of drugs that cause arterial hypotension, ACE inhibitors can block the formation of angiotensin II in response to compensatory release of renin. If this results in a pronounced decrease in blood pressure, explained by such a mechanism, it can be corrected by increasing the volume of circulating blood.

Liver failure

In rare cases, against the background of the use of ACE inhibitors there is cholestatic jaundice, with the progression of which fulminant liver necrosis develops, sometimes with a lethal outcome. When jaundice or a significant increase in the activity of "liver" transaminases against the background of the use of ACE inhibitors, the use of Enalapril-Acry® should be discontinued.

Neutropenia / agranulocytosis

In patients who took ACE inhibitors, cases of development of neutropenia / agranulocytosis, thrombocytopenia and anemia were noted.In patients with normal renal function in the absence of other complications, neutropenia develops rarely. Enalapril-Acry® should be used with great care in patients with connective tissue diseases (including systemic lupus erythematosus, scleroderma), simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, as well as a combination of these factors, especially with existing violations of kidney function. These patients can develop severe infections that are not amenable to intensive antibiotic therapy. If patients still take Enalapril-Acry®, it is recommended to periodically monitor the number of white blood cells in the blood. The patient should be warned that if there are any signs of infection, you should immediately consult a doctor.

Patients with diabetes mellitus

When using Enalapril-Acry® in patients with diabetes mellitus receiving hypoglycemic agents for ingestion or insulin, during the first month of therapy it is necessary to regularly monitor the concentration of glucose in the blood.

Lithium

Simultaneous use of lithium drugs and Enalapril-Acry® is usually not recommended.

Hyperkalemia

It can develop during treatment with ACE inhibitors, including enalapril. Risk factors for hyperkalemia are renal failure, advanced age, diabetes, some comorbid conditions (reduction of BCC, acute heart failure decompensation, metabolic acidosis), simultaneous reception of potassium-sparing diuretics (such as spnronolakton, triamterene, amiloride), and potassium drugs or potassium-based salt substitutes and the use of other drugs that enhance the potassium content in the blood plasma (e.g., heparin).

Hyperkalemia can lead to serious heart rhythm disturbances, sometimes with a fatal outcome. Combined use of the above drugs should be done with caution.

Cough

In applying the drug enalapril-Akri® may be "dry", prolonged cough, which disappears after discontinuation of ACE inhibitors that should be considered in the differential diagnosis of cough during treatment with an ACE inhibitor.

Ethnic Features

The drug Enalapril-Acry®, like other ACE inhibitors, has a less pronounced antihypertensive effect in patients of the Negroid race compared with representatives of other races.

Effect on the ability to drive transp. cf. and fur:

When using Enalapril-Acry®, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets 5 mg and 10 mg.

Packaging:

For 10 tablets in a planar cell package.

2, 3 or 10 contour squares, together with instructions for use in a pack of cardboard.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N002606 / 01

Date of registration:19.05.2008

Date of cancellation:2018-04-12

The owner of the registration certificate:AKRIKHIN HFK, JSC AKRIKHIN HFK, JSC Russia

Manufacturer: & nbsp

AKRIKHIN HFK, JSC Russia

Information update date: & nbsp12.04.2018

Illustrated instructions

Instructions

Enalapril-Acry® (Enalapril-Akri®)