Sustained results from enalapril in the treatment of hypertension. Enalapril - instructions for use Enalapril 2.5 mg instructions for use

Carefully. Aortic and/or mitral stenosis (with hemodynamic disturbances); hypertrophic obstructive cardiomyopathy (HOCM); cerebrovascular diseases (including cerebrovascular insufficiency); coronary heart disease (CHD); autoimmune systemic connective tissue diseases (including scleroderma, systemic lupus erythematosus); inhibition of bone marrow hematopoiesis; condition after kidney transplantation; renal failure (creatinine clearance less than 80 ml/min), liver failure; a history of severe allergies or angioedema; use in patients of the Negroid race; during the procedure of low-density lipoprotein (LDL) apheresis using dextran sulfate; in patients undergoing dialysis using high-flux membranes (such as AN69); in patients after major surgery or during general anesthesia; renovascular hypertension; during desensitization with an allergen from Hymenoptera venom; patients on a diet with limited salt intake or on hemodialysis; hyperkalemia; conditions accompanied by a decrease in circulating blood volume (CBV), incl. diarrhea, vomiting; old age (over 65 years), primary aldosteronism, diabetes mellitus, simultaneous use with immunosuppressants and saluretics. Use during pregnancy and breastfeeding. The use of the drug during pregnancy is not recommended. If pregnancy occurs, the drug should be stopped immediately. ACE inhibitors can cause disease or death of the fetus or newborn when used in the second and third trimesters of pregnancy. The use of an ACE inhibitor during this period was associated with adverse effects on the fetus and newborn, including the development of arterial hypotension, renal failure, hyperkalemia and/or hypoplasia of the skull in the newborn. Oligohydramnios may develop, apparently due to decreased fetal renal function. This complication can lead to contracture of the limbs, deformation of the bones of the skull, including its facial part, and hypoplasia of the lungs. When using the drug, it is necessary to inform the patient about the potential risk to the fetus. Newborns whose mothers took the drug should be carefully monitored for hypotension, oliguria, and hyperkalemia. A drug that crosses the placenta may be partially removed from the neonatal circulation by peritoneal dialysis; theoretically it can be removed through exchange transfusion. Prematurity, intrauterine growth restriction, and patent ductus arteriosus have also been reported, but it is unclear whether these cases were related to the effects of the ACE inhibitor. In those rare cases where the use of an ACE inhibitor during pregnancy is considered necessary, periodic ultrasound examinations should be performed to assess the amniotic fluid index. If oligohydramnios is detected during an ultrasound examination, it is necessary to stop taking the drug, unless its use is considered vital for the mother. However, both the patient and the physician should be aware that oligohydramnios occurs when there is irreversible damage to the fetus. If ACE inhibitors are used during pregnancy and the development of oligohydramnios is observed, then, depending on the week of pregnancy, a stress test, a non-stress test or a fetal biophysical profile may be necessary to assess the functional status of the fetus. Enalapril and enalaprilat are excreted in breast milk in trace concentrations. If it is necessary to use the drug Enalapril during lactation, breastfeeding should be discontinued. The issue of using dual blockade of the RAAS (for example, by simultaneous use of an ACE inhibitor with an angiotensin II receptor antagonist) must be decided on a case-by-case basis with careful monitoring of renal function. Caution must be exercised in patients with reduced blood volume (including when used simultaneously with diuretics, in conditions of limited salt intake, with hemodialysis, diarrhea, vomiting), in whom a sudden and pronounced decrease in blood pressure may develop in response to the use of an ACE inhibitor. In patients with mild CHF, with or without chronic renal failure, symptomatic hypotension is usually not observed. The development of arterial hypotension is most likely in patients with more severe CHF due to the use of high doses of diuretics, hyponatremia or functional renal failure. In these patients, treatment should begin under medical supervision until the optimal dose adjustment of Enalapril and/or diuretic is achieved. Similar tactics can be applied to patients with coronary artery disease and cerebrovascular diseases in whom an excessive decrease in blood pressure can lead to myocardial infarction or cerebrovascular accident. If severe arterial hypertension develops, the patient should be placed in a horizontal position and, if necessary, an intravenous infusion of 0.9% sodium chloride solution should be started. Transient arterial hypotension is not a contraindication for continuing treatment with Enalapril after stabilization of blood pressure and replenishment of blood volume. In some patients with CHF with normal or low blood pressure, an additional decrease in blood pressure may occur when using the drug Enalapril. This is usually not a reason to discontinue the drug. If arterial hypotension develops, it is necessary to reduce the dose and/or discontinue the diuretic and/or enalapril. As with all vasodilators, ACE inhibitors should be used with caution in patients with left ventricular hypertrophy and valvular obstruction and should be avoided in cases of cardiogenic shock and hemodynamically significant obstruction. In case of impaired renal function (creatinine clearance less than 80 ml/min), careful monitoring of potassium and creatinine levels in the blood serum is necessary. In patients with renal failure, it may be necessary to reduce the dose and/or frequency of dosing. Some patients with bilateral renal artery stenosis or arterial stenosis of a solitary kidney experience increased serum urea and creatinine concentrations. The changes are usually reversible and return to normal after stopping treatment. In some patients who did not have renal disease before treatment, slight and transient increases in serum urea and creatinine concentrations were observed when enalapril was used concomitantly with diuretics. In such cases, it may be necessary to reduce the dose and/or discontinue enalapril and/or diuretic. Patients with bilateral renal artery stenosis or arterial stenosis of a solitary kidney taking ACE inhibitors are at increased risk of developing hypotension and renal failure. Only moderate changes in plasma creatinine concentration can indicate a decrease in renal function. In such patients, treatment should begin with small doses under medical supervision, gradually selecting an individual dose and monitoring the concentration of creatinine in the blood serum. There is no experience with the use of enalapril in patients who have recently undergone kidney transplantation. Therefore, the use of this drug in such patients is not recommended. The use of Enalapril in patients with liver failure usually does not require dose adjustment. Rarely, taking an ACE inhibitor is associated with a syndrome ranging from the development of cholestatic jaundice to the development of fulminant liver necrosis. If symptoms of jaundice or increased liver enzyme activity occur in patients taking ACE inhibitors, discontinue drug therapy and conduct appropriate evaluation. Cases of neutropenia/agranulocytosis, thrombocytopenia and anemia have been reported in patients taking ACE inhibitors. Neutropenia rarely develops in patients with normal renal function and no other complications. The drug Enalapril should be used with great caution in patients with connective tissue diseases (including systemic lupus erythematosus, scleroderma) who are simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, as well as a combination of these factors, especially with existing renal dysfunction. These patients may develop severe infections that do not respond to intensive antibiotic therapy. If patients still take the drug Enalapril, it is recommended to periodically monitor the number of leukocytes in the blood. The patient should be warned that if any signs of infection appear, they should consult a doctor. Angioedema of the face, extremities, tongue, vocal cords and/or larynx has been reported with the use of ACE inhibitors, including enalapril. This can happen at any time during treatment. In such cases, treatment with Enalapril should be stopped immediately, and the patient should be under medical supervision until the corresponding symptoms completely disappear. Even in cases where only difficulty in swallowing occurs without difficulty breathing, patients may require long-term medical observation because Therapy with antihistamines and glucocorticosteroids may not be enough. Angioedema, associated with swelling of the larynx and tongue, can be fatal in very rare cases. Patients with swelling of the tongue, vocal cords, or larynx may develop airway obstruction, especially in patients with a history of respiratory surgery. In cases of airway obstruction, it is necessary to carry out appropriate therapy as soon as possible, including subcutaneous administration of epinephrine (0.3-0.5 ml of epinephrine (adrenaline) solution in a ratio of 1:1000) and/or take the necessary measures to ensure the conductivity of the airways ( intubation or tracheostomy). Among black patients receiving ACE inhibitor therapy, the incidence of angioedema is higher than among patients of other races. Patients with a history of angioedema not associated with the use of ACE inhibitors are at increased risk of developing angioedema when taking any ACE inhibitor. There are reports of the development of life-threatening anaphylactic reactions in patients taking ACE inhibitors during the desensitization procedure with hymenoptera venom. Such reactions can be avoided if you temporarily stop taking ACE inhibitors before desensitization begins. The use of ACE inhibitors should be avoided in patients receiving bee venom immunotherapy. In rare cases, life-threatening anaphylactoid reactions have been observed in patients taking ACE inhibitors during LDL apheresis with dextran sulfate. If LDL apheresis is used, ACE inhibitors should be temporarily replaced with other drugs to treat hypertension and heart failure. Anaphylactoid reactions have been reported in patients undergoing hemodialysis using high-flux polyacrylonitrile membranes (AN69). In these cases, it is recommended to use a different type of membrane for dialysis or use an antihypertensive drug of a different pharmacotherapeutic group. When using Enalapril in patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, blood glucose concentrations should be regularly monitored during the first month of therapy. Cough has been reported with the use of ACE inhibitors. Usually the cough is non-productive and persistent and stops after discontinuation of ACE inhibitors. In the differential diagnosis of cough, cough caused by the use of ACE inhibitors must also be taken into account. In patients undergoing surgery or during general anesthesia with drugs that cause hypotension, ACE inhibitors may block the formation of angiotensin II in response to compensatory release of renin. Before surgery (including dental procedures), it is necessary to warn the surgeon-anesthesiologist about the use of the drug Enalapril. Hyperkalemia may develop during therapy with ACE inhibitors, including enalapril. Risk factors for hyperkalemia are renal failure, old age (over 65 years), diabetes mellitus, some concomitant conditions (decrease in blood volume, acute heart failure in the stage of decompensation, metabolic acidosis), simultaneous use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride ), as well as potassium preparations or potassium-containing substitutes for table salt and the use of other drugs that help increase the content of potassium in the blood plasma (for example, heparin). The use of potassium supplements, potassium-sparing diuretics or potassium-containing table salt substitutes, especially in patients with renal failure, can lead to a significant increase in plasma potassium levels. Hyperkalemia can cause serious heart rhythm disturbances, sometimes fatal. The simultaneous use of Enalapril with any of the drugs listed above should be carried out with caution and should be accompanied by regular monitoring of potassium levels in the blood plasma. The simultaneous use of lithium and Enalapril is usually not recommended. The drug Enalapril, like other ACE inhibitors, has a less pronounced antihypertensive effect in patients of the Black race compared to representatives of other races, possibly due to low renin activity in patients with arterial hypertension in this population. Sudden cessation of enalapril does not lead to the development of withdrawal syndrome. Impact on the ability to drive vehicles and machinery. When using the drug Enalapril, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions, due to the possibility of developing dizziness and drowsiness.

P N013864/01

Trade name of the drug: ENALAPRIL

International nonproprietary name:

Enalapril

Dosage form:

pills

Compound:

1 tablet 5 mg contains:
Active substance: enalapril maleate - 5 mg.
Excipients: lactose monohydrate - 106,000 mg, magnesium carbonate - 71,645 mg, gelatin - 7,800 mg, crospovidone - 7,800 mg, magnesium stearate - 1,755 mg.
1 tablet 10 mg contains:
Active substance: enalapril maleate - 10 mg.
Excipients: lactose monohydrate - 125,000 mg, magnesium carbonate - 84,600 mg, gelatin - 9,200 mg, crospovidone - 9,200 mg, magnesium stearate - 2,000 mg.
1 tablet 20 mg contains:
Active substance: enalapril maleate - 20 mg.
Excipients: lactose monohydrate - 116,400 mg, magnesium carbonate - 120,000 mg, gelatin - 10,700 mg, crospovidone - 10,700 mg, magnesium stearate - 2,200 mg.

Description
For tablets 5 mg, 10 mg and 20 mg - round, biconvex white tablets with a score on one side.

Pharmacotherapeutic group:

angiotensin-converting enzyme inhibitor.

ATX Code:[С09АА02]

Pharmacological properties
Pharmacodynamics
Enalapril is an antihypertensive drug from the group of ACE inhibitors. Enalapril is a “prodrug”: as a result of its hydrolysis, enalaprilat is formed, which inhibits ACE. The mechanism of its action is associated with a decrease in the formation of angiotensin II from angiotensin I, a decrease in the content of which leads to a direct decrease in the release of aldosterone. At the same time, total peripheral vascular resistance, systolic and diastolic blood pressure (BP), post- and preload on the myocardium decrease.
It dilates arteries to a greater extent than veins, while there is no reflex increase in heart rate.
The hypotensive effect is more pronounced with high plasma renin levels than with normal or reduced levels. A decrease in blood pressure within therapeutic limits does not affect cerebral circulation; blood flow in the vessels of the brain is maintained at a sufficient level even against the background of reduced blood pressure.
Strengthens coronary and renal blood flow.
With long-term use, hypertrophy of the left ventricle of the myocardium and myocytes of the walls of resistive arteries decreases, prevents the progression of heart failure and slows down the development of left ventricular dilatation. Improves blood supply to ischemic myocardium. Reduces platelet aggregation.
Has some diuretic effect.
The onset of the hypotensive effect when taken orally is 1 hour, reaches a maximum after 4–6 hours and lasts up to 24 hours. In some patients, therapy is required for several weeks to achieve an optimal level of blood pressure. In heart failure, a noticeable clinical effect is observed with long-term use - 6 months or more.
Pharmacokinetics
After oral administration, 60% of the drug is absorbed. Eating does not affect the absorption of enalapril. Enalapril is up to 50% bound to blood proteins. Enalapril is rapidly metabolized in the liver to form the active metabolite enalaprilat, which is a more active ACE inhibitor than enalapril. Bioavailability of the drug is 40%. The maximum concentration of enalapril in the blood plasma is achieved after 1 hour, enalaprilat - after 3–4 hours. Enalaprilat easily passes through histohematic barriers, excluding the blood-brain barrier; a small amount penetrates the placenta and into breast milk.
The half-life of enalaprilat is about 11 hours. Enalapril is excreted mainly by the kidneys - 60% (20% in the form of enalapril and 40% in the form of enalaprilat), through the intestines - 33% (6% in the form of enalapril and 27% in the form of enalaprilat ).
It is removed by hemodialysis (rate - 62 ml/min) and peritoneal dialysis.

Indications for use
- arterial hypertension,
- for chronic heart failure (as part of combination therapy).

Contraindications
Hypersensitivity to enalapril and other ACE inhibitors, a history of angioedema associated with treatment with ACE inhibitors, porphyria, pregnancy, lactation, age under 18 years (efficacy and safety have not been established).
Carefully used for primary hyperaldosteronism, bilateral renal artery stenosis, stenosis of the artery of a single kidney, hyperkalemia, condition after kidney transplantation; aortic stenosis, mitral stenosis (with hemodynamic disorders), idiopathic hypertrophic subaortic stenosis, systemic connective tissue diseases, coronary heart disease, cerebrovascular diseases, diabetes mellitus, renal failure (proteinuria - more than 1 g / day), liver failure, in patients observing a diet with limited salt or those on hemodialysis, while taking immunosuppressants and saluretics, in elderly people (over 65 years of age).

Directions for use and doses
Prescribed orally regardless of meal time.
For monotherapy of arterial hypertension, the initial dose is 5 mg once a day.
If there is no clinical effect, the dose is increased by 5 mg after 1–2 weeks. After taking the initial dose, patients should be under medical supervision for 2 hours and an additional 1 hour until blood pressure stabilizes. If necessary and sufficiently well tolerated, the dose can be increased to 40 mg/day in 2 divided doses. After 2–3 weeks, switch to a maintenance dose of 10–40 mg/day, divided into 1–2 doses. For moderate arterial hypertension, the average daily dose is about 10 mg.
The maximum daily dose of the drug is 40 mg/day.
If prescribed to patients concomitantly receiving diuretics, diuretic treatment should be discontinued 2-3 days before Enalapril is prescribed. If this is not possible, then the initial dose of the drug should be 2.5 mg/day.
For patients with hyponatremia (concentration of sodium ions in the blood serum less than 130 mmol/l) or a concentration of creatinine in the blood serum more than 0.14 mmol/l, the initial dose is 2.5 mg 1 time per day.
For renovascular hypertension, the initial dose is 2.5–5 mg/day. The maximum daily dose is 20 mg.
For 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 in accordance with the clinical response to the maximum tolerated dose depending on blood pressure, but not higher than 40 mg/day. day once or in 2 doses. In patients with low systolic blood pressure (less than 110 mm Hg), therapy should begin with a dose of 1.25 mg/day. Dose selection should be carried out over 2–4 weeks or shorter periods. The average maintenance dose is 5–20 mg/day. in 1–2 doses.
In elderly people, a more pronounced hypotensive effect and a prolongation of the duration of action of the drug are often observed, which is associated with a decrease in the rate of elimination of enalapril, therefore the recommended initial dose for elderly people is 1.25 mg.
In chronic renal failure, cumulation occurs when filtration decreases to less than 10 ml/min. With a creatinine clearance (CC) of 80–30 ml/min, the dose is usually 5–10 mg/day, with a creatinine clearance of up to 30–10 ml/min - 2.5–5 mg/day, with a creatinine clearance of less than 10 ml/min. - 1.25–2.5 mg/day. only on dialysis days.
The duration of treatment depends on the effectiveness of the therapy. If the decrease in blood pressure is too pronounced, the dose of the drug is gradually reduced.
The drug is used both in monotherapy and in combination with other antihypertensive drugs. Side effect
Enalapril is generally well tolerated and in most cases does not cause side effects requiring discontinuation of the drug.
From the cardiovascular system: excessive decrease in blood pressure, orthostatic collapse, rarely - chest pain, angina pectoris, myocardial infarction (usually associated with a pronounced decrease in blood pressure), extremely rarely - arrhythmias (atrial brady- or tachycardia, atrial fibrillation), palpitations, thromboembolism of the branches of the pulmonary artery.
From the nervous system: dizziness, headache, weakness, insomnia, anxiety, confusion, fatigue, drowsiness (2–3%), very rarely when using high doses - nervousness, depression, paresthesia.
From the senses: disorders of the vestibular apparatus, hearing and vision impairment, tinnitus.
From the digestive tract: dry mouth, anorexia, dyspeptic disorders (nausea, diarrhea or constipation, vomiting, abdominal pain), intestinal obstruction, pancreatitis, impaired liver function and bile secretion, hepatitis, jaundice.
From the respiratory system: nonproductive dry cough, interstitial pneumonitis, bronchospasm, shortness of breath, rhinorrhea, pharyngitis.
Allergic reactions: skin rash, itching, urticaria, angioedema, extremely rarely - dysphonia, erythema multiforme, exfoliative dermatitis, Steven-Johnson syndrome, toxic epidermal necrolysis, pemphigus, photosensitivity, serositis, vasculitis, myositis, arthralgia, arthritis, stomatitis, glossitis.
From the laboratory parameters: hypercreatininemia, increased urea content, increased activity of liver enzymes, hyperbilirubinemia, hyperkalemia, hyponatremia. In some cases, a decrease in hematocrit, an increase in ESR, thrombocytopenia, neutropenia, agranulocytosis (in patients with autoimmune diseases), and eosinophilia are noted.
From the urinary system: renal dysfunction, proteinuria. Other: alopecia, decreased libido, hot flashes.

Overdose
Symptoms: a pronounced decrease in blood pressure up to the development of collapse, myocardial infarction, acute cerebrovascular accident or thromboembolic complications, convulsions, stupor.
Treatment: the patient is transferred to a horizontal position with a low headboard. In mild cases, gastric lavage and ingestion of saline solution are indicated; in more severe cases, measures aimed at stabilizing blood pressure are indicated: intravenous administration of saline, plasma substitutes, if necessary, administration of angiotensin II, hemodialysis (the elimination rate of enalaprilat is on average 62 ml/min ).

Interaction with other drugs
When Enalapril is co-administered with non-steroidal anti-inflammatory drugs (NSAIDs), the hypotensive effect may be reduced; with potassium-sparing diuretics (spironolactone, triamterene, amiloride) can lead to hyperkalemia; with lithium salts - to slow down the excretion of lithium (monitoring the concentration of lithium in the blood plasma is indicated).

Concomitant use with antipyretics and analgesics may reduce the effectiveness of enalapril.

Enalapril weakens the effect of drugs containing theophylline.

The hypotensive effect of enalapril is enhanced by diuretics, beta-blockers, methyldopa, nitrates, blockers of “slow” calcium channels, hydralazine, prazosin.

Immunosuppressants, allopurinol, cytostatics increase hematotoxicity.

Drugs that cause bone marrow suppression increase the risk of developing neutropenia and/or agranulocytosis.

special instructions
Caution must be exercised when prescribing Enalapril to patients with reduced circulating blood volume (as a result of diuretic therapy, limiting salt intake, hemodialysis, diarrhea and vomiting) - there is an increased risk of a sudden and pronounced decrease in blood pressure after using even the initial dose of an ACE inhibitor. Transient arterial hypotension is not a contraindication for continuing treatment with the drug after stabilization of blood pressure. In case of a repeated pronounced decrease in blood pressure, the dose should be reduced or the drug discontinued.
The use of highly permeable dialysis membranes increases the risk of developing an anaphylactic reaction. Correction of the dosage regimen on days free from dialysis should be carried out depending on the level of blood pressure.

Before and during treatment with ACE inhibitors, periodic monitoring of blood pressure, blood parameters (hemoglobin, potassium, creatinine, urea, liver enzyme activity), and protein in the urine is necessary.

Patients with severe heart failure, coronary artery disease, and cerebrovascular disease, in whom a sharp decrease in blood pressure may lead to myocardial infarction, stroke, or dysfunction, should be carefully monitored

Sudden cessation of treatment does not lead to withdrawal syndrome (a sharp rise in blood pressure).

For newborns and infants who have been exposed in utero to ACE inhibitors, it is recommended to conduct careful monitoring for timely detection of a pronounced decrease in blood pressure, oliguria, hyperkalemia and neurological disorders that may be due to a decrease in renal and cerebral blood flow with a decrease in blood pressure caused by ACE inhibitors. In oliguria, it is necessary to maintain blood pressure and renal perfusion by administering appropriate fluids and vasoconstrictors. In the presence of renal failure, the excretion of the active metabolite may be reduced, leading to an increase in its concentration in the blood plasma. Such patients may need to be prescribed smaller doses of the drug.

In patients with arterial hypertension and unilateral or bilateral renal artery stenosis, an increase in urea and creatinine in the blood serum is possible.

In such patients, renal function should be monitored during the first few weeks of therapy. It may be necessary to reduce the dosage of the drug.

The balance of risk and potential benefit should be taken into account when prescribing Enalapril to patients with coronary and cerebrovascular insufficiency, due to the risk of increased ischemia with excessive arterial hypotension.

The drug should be prescribed with caution to patients with diabetes mellitus due to the risk of developing hyperkalemia.

Patients with a history of angioedema may have an increased risk of developing angioedema during treatment with Enalapril.
Patients with severe autoimmune diseases, such as systemic lupus erythematosus or scleroderma, are at increased risk of developing neutropenia or agranulocytosis while taking Enalapril.

Before studying the functions of the parathyroid glands, the drug should be discontinued.

Alcohol enhances the hypotensive effect of the drug.

At the beginning of treatment, until the completion of the dose selection period, it is necessary to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions, as dizziness is possible, especially after the initial dose of an ACE inhibitor in patients taking diuretics.

Before surgery (including dentistry), the surgeon/anesthesiologist must be warned about the use of ACE inhibitors.

Release form
Tablets 5 mg, 10 mg, 20 mg.
10 tablets per blister made of A1/A1, laminated with PVC and polyamide film. 2 blisters along with instructions for use are placed in a cardboard pack.

Storage conditions
List B.
Store in a dry place, at a temperature of 15 to 25 °C.
Keep out of the reach of children.

Best before date
3 years.
Do not use after expiration date.

Conditions for dispensing from pharmacies
On prescription.

Manufacturer
1. Manufacturer
Hemofarm A.D., Serbia
26300 Vršac, Beogradski put bb, Serbia
Consumer complaints should be sent to:
Russia, 603950, Nizhny Novgorod GSP-458, st. Salganskaya, 7.
In the case of packaging at Hemofarm LLC. Russia:
Manufactured by: Hemofarm A.D., Vršac, Serbia
Packed:

Hemofarm LLC, 249030, Russia, Kaluga region, Obninsk, Kyiv highway, 62.

OR
2. Manufacturer
Hemofarm LLC, 249030, Russia, Kaluga region, Obninsk, Kyiv highway, 62.
Organizations accepting complaints from consumers:
Hemofarm LLC, 249030, Russia, Kaluga region, Obninsk, Kyiv highway, 62.

Enalapril maleate (enalapril)

Composition and release form of the drug

Pills from white to white with a yellowish tint, round, biconvex.

Excipients: microcrystalline cellulose - 73 mg, pregelatinized corn starch - 30 mg, talc - 3 mg, colloidal silicon dioxide - 1 mg, magnesium stearate - 1 mg.

10 pieces. - contour cellular packaging (1) - cardboard packs.
10 pieces. - contour cellular packaging (2) - cardboard packs.
10 pieces. - contour cellular packaging (3) - cardboard packs.
10 pieces. - contour cellular packaging (5) - cardboard packs.
10 pieces. - contour cellular packaging (10) - cardboard packs.

pharmachologic effect

ACE inhibitor. It is a prodrug from which the active metabolite enalaprilat is formed in the body. It is believed that the mechanism of antihypertensive action is associated with competitive inhibition of ACE activity, which leads to a decrease in the rate of conversion of angiotensin I to angiotensin II (which has a pronounced vasoconstrictor effect and stimulates the secretion of aldosterone in the adrenal cortex).

As a result of a decrease in the concentration of angiotensin II, there is a secondary increase in renin activity due to the elimination of negative feedback on the release of renin and a direct decrease in aldosterone secretion. In addition, enalaprilat appears to have an effect on the kinin-kallikrein system, preventing the breakdown of bradykinin.

Thanks to its vasodilating effect, it reduces roundabout percentage (afterload), wedge pressure in the pulmonary capillaries (preload) and resistance in the pulmonary vessels; increases cardiac output and exercise tolerance.

In patients with chronic heart failure, with long-term use, enalapril increases exercise tolerance and reduces the severity of heart failure (assessed by NYHA criteria). Enalapril in patients with mild to moderate heart failure slows its progression and also slows down the development of left ventricular dilatation. In case of left ventricular dysfunction, enalapril reduces the risk of major ischemic outcomes (including the incidence of myocardial infarction and the number of hospitalizations for unstable angina).

Pharmacokinetics

When taken orally, about 60% is absorbed from the gastrointestinal tract. Concomitant food intake does not affect absorption. Metabolized in the liver by hydrolysis with the formation of enalaprilat, due to the pharmacological activity of which a hypotensive effect is realized. The binding of enalaprilat to plasma proteins is 50-60%.

T1/2 of enalaprilat is 11 hours and increases with renal failure. After oral administration, 60% of the dose is excreted by the kidneys (20% as enalapril, 40% as enalaprilat), 33% is excreted through the intestines (6% as enalapril, 27% as enalaprilat). After intravenous administration of enalaprilat, 100% is excreted unchanged by the kidneys.

Indications

Arterial hypertension (including renovascular), chronic failure (as part of combination therapy).

Essential hypertension.

Chronic heart failure (as part of combination therapy).

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

Prevention of coronary ischemia in patients with left ventricular dysfunction in order to reduce the incidence of myocardial infarction and reduce the frequency of hospitalizations for unstable angina.

Contraindications

History of angioedema, bilateral renal artery stenosis or renal artery stenosis of a solitary kidney, hyperkalemia, porphyria, concomitant use with aliskiren in patients with diabetes mellitus or impaired renal function (CK<60 мл/мин), беременность, период лактации (грудного вскармливания), детский и подростковый возраст до 18 лет, повышенная чувствительность к эналаприлу и другим ингибиторам АПФ.

Dosage

When taken orally, the initial dose is 2.5-5 mg 1 time / day. The average dose is 10-20 mg/day in 2 divided doses.

Maximum daily dose when taken orally it is 80 mg.

Side effects

From the nervous system: dizziness, headache, feeling tired, increased fatigue; very rarely when used in high doses - sleep disorders, nervousness, depression, imbalance, paresthesia, tinnitus.

From the cardiovascular system: orthostatic hypotension, fainting, palpitations, pain in the heart area; very rarely when used in high doses - hot flashes.

From the digestive system: nausea; rarely - dry mouth, abdominal pain, vomiting, diarrhea, constipation, impaired liver function, increased activity of liver transaminases, increased concentration of bilirubin in the blood, hepatitis, pancreatitis; very rarely when used in high doses - glossitis.

From the hematopoietic system: rarely - neutropenia; in patients with autoimmune diseases - agranulocytosis.

From the urinary system: rarely - renal dysfunction, proteinuria.

From the respiratory system: dry cough.

From the reproductive system: very rarely, when used in high doses - impotence.

Dermatological reactions: very rarely when used in high doses - hair loss.

Allergic reactions: rarely - skin rash, Quincke's edema.

Others: rarely - hyperkalemia, muscle cramps.

Drug interactions

When used simultaneously with cytostatics, the risk of developing leukopenia increases.

With the simultaneous use of potassium-sparing diuretics (including spironolactone, triamterene, amiloride), potassium supplements, salt substitutes and dietary supplements containing potassium, hyperkalemia may develop (especially in patients with impaired renal function), because ACE inhibitors reduce the content of aldosterone, which leads to potassium retention in the body while limiting the excretion of potassium or its additional intake into the body.

With the simultaneous use of opioids and anesthetics, the antihypertensive effect of enalapril is enhanced.

With the simultaneous use of loop diuretics and thiazide diuretics, the antihypertensive effect is enhanced. There is a risk of developing hypokalemia. Increased risk of renal dysfunction.

When used simultaneously with azathioprine, anemia may develop, which is due to inhibition of erythropoietin activity under the influence of ACE inhibitors and azathioprine.

A case of the development of an anaphylactic reaction and myocardial infarction with the use of allopurinol in a patient receiving enalapril is described.

In high doses, it may reduce the antihypertensive effect of enalapril.

It has not been conclusively established whether acetylsalicylic acid reduces the therapeutic effectiveness of ACE inhibitors in patients with coronary artery disease and heart failure. The nature of this interaction depends on the course of the disease.

Acetylsalicylic acid, by inhibiting COX and prostaglandin synthesis, can cause vasoconstriction, which leads to a decrease in cardiac output and worsening of the condition of patients with heart failure receiving ACE inhibitors.

With the simultaneous use of beta-blockers, methyldopa, nitrates, hydralazine, prazosin, the antihypertensive effect may be enhanced.

When used simultaneously with NSAIDs (including indomethacin), the antihypertensive effect of enalapril is reduced, apparently due to inhibition of the synthesis of prostaglandins under the influence of NSAIDs (which are believed to play a role in the development of the hypotensive effect of ACE inhibitors). The risk of developing renal dysfunction increases; hyperkalemia is rarely observed.

With the simultaneous use of insulin and hypoglycemic agents, sulfonylurea derivatives, hypoglycemia may develop.

With simultaneous use of ACE inhibitors and interleukin-3, there is a risk of developing arterial hypotension.

When used concomitantly, there are reports of the development of syncope.

When used simultaneously with clomipramine, increased effects of clomipramine and the development of toxic effects are reported.

When used simultaneously with co-trimoxazole, cases of hyperkalemia have been described.

When used simultaneously with lithium carbonate, the concentration of lithium in the blood serum increases, which is accompanied by symptoms of lithium intoxication.

When used simultaneously with orlistat, the antihypertensive effect of enalapril is reduced, which can lead to a significant increase in blood pressure and the development of a hypertensive crisis.

It is believed that when used simultaneously with procainamide, there may be an increased risk of developing leukopenia.

When used simultaneously with enalapril, the effect of drugs containing theophylline is reduced.

There are reports of the development of acute renal failure in patients after kidney transplantation when used simultaneously with cyclosporine.

When used simultaneously with cimetidine, the half-life of enalapril increases and its concentration in the blood plasma increases.

It is believed that the effectiveness of antihypertensive drugs may be reduced when used simultaneously with erythropoietins.

When used simultaneously with ethanol, the risk of developing arterial hypotension increases.

special instructions

Use with extreme caution in patients with autoimmune diseases, diabetes mellitus, liver dysfunction, severe aortic stenosis, subaortic muscular stenosis of unknown origin, hypertrophic cardiomyopathy, and loss of fluid and salts. In the case of previous treatment with saluretics, in particular in patients with chronic heart failure, the risk of developing orthostatic hypotension increases, therefore, before starting treatment with enalapril, it is necessary to compensate for the loss of fluid and salts.

With long-term treatment with enalapril, it is necessary to periodically monitor the peripheral blood picture. Sudden cessation of enalapril does not cause a sharp increase in blood pressure.

During surgical interventions during treatment with enalapril, arterial hypotension may develop, which should be corrected by administering a sufficient amount of fluid.

Before studying the function of the parathyroid glands, enalapril should be discontinued.

Impact on the ability to drive vehicles and machinery

Caution is required when driving vehicles or performing other work that requires increased attention, because Dizziness may occur, especially after taking the initial dose of enalapril.

Pregnancy and lactation

Contraindicated for use during pregnancy. If pregnancy occurs, enalapril should be stopped immediately.

Enalapril is excreted in breast milk. If it is necessary to use it during lactation, the issue of stopping breastfeeding should be decided.

Use in childhood

The safety and effectiveness of enalapril in children have not been established.

For liver dysfunction

Use with extreme caution in patients with impaired liver function.

Enalapril is an angiotensin-converting enzyme (ACE) inhibitor. The human body is a collection of many biochemical reactions that control its vital activity at the cellular level. The renin-angiotensin-aldosterone system is one of these cycles of sequential transformations of biologically active substances, which plays an important role in the regulation of blood pressure and water-salt balance. By inactivating one of the important links in this cycle - angiotensin - enalapril thereby prevents the formation of the adrenal hormone aldosterone, which, in turn, causes a decrease in blood pressure.

Enalapril is an indispensable remedy in the first aid kit for every patient suffering from hypertension. In addition to the hypotensive effect, it also has many positive qualities regarding the cardiovascular system. This includes a reduction in excess vascular tone, a reduction in the load on the heart muscle, and a mild diuretic effect. The pronounced effect of a single dose of the drug is felt 4-6 hours after administration and persists throughout the day. However, one should not expect miracles from it here and now: people with heart failure need to take enalapril for at least 6 months to achieve a clear clinical effect.

The advantage of enalapril is that there is no need to make allowances for your daily gastronomic routine: it can be taken at any time, regardless of meals. There are many regimens for taking this drug, depending on the disease and the age of the patient. As a general rule, when treating arterial hypertension with enalapril in the “solo” mode, the initial daily dose is 5 mg. If there are no obvious results, after 7-14 days the dose is increased by another 5 mg and so on up to 40 mg, above which you should not rise.

Elderly patients are more susceptible to the action of enalapril, which is manifested in a slightly more pronounced and long-lasting hypotensive effect. This is explained by the reduced rate of excretion of enalapril in older patients. In such cases, the initial daily dose is recommended to be reduced to 1.25 mg.

Enalapril works well both in combination with other antihypertensive drugs and on its own. The timing of taking the drug depends on the observed effect. The dose of the drug at which its clear therapeutic effect was achieved is not an unshakable constant and can subsequently be reduced to maintenance values.

Pharmacology

As a result of a decrease in the concentration of angiotensin II, a secondary increase in plasma renin activity occurs due to the elimination of negative feedback during the release of renin and a direct decrease in aldosterone secretion. In addition, enalaprilat appears to have an effect on the kinin-kallikrein system, preventing the breakdown of bradykinin.

Pharmacokinetics

Release form

10 pieces. - contour cellular packaging (1) - cardboard packs.
10 pieces. - contour cell packaging (2) - cardboard packs.
10 pieces. - contour cell packaging (3) - cardboard packs.
10 pieces. - contour cell packaging (5) - cardboard packs.
10 pieces. - contour cellular packaging (2) - cardboard packs.
20 pcs. - contour cellular packaging (1) - cardboard packs.
20 pcs. - contour cellular packaging (2) - cardboard packs.

Dosage

When taken orally, the initial dose is 2.5-5 mg 1 time / day. The average dose is 10-20 mg/day in 2 divided doses.

With intravenous administration, 1.25 mg every 6 hours. To detect excessive hypotension, patients with sodium deficiency and dehydration due to previous diuretic therapy, patients receiving diuretics, as well as with renal failure, administer an initial dose of 625 mg. If the clinical response is inadequate, this dose can be repeated after 1 hour and treatment continued at a dose of 1.25 mg every 6 hours.

The maximum daily dose when taken orally is 80 mg.

Interaction

When used simultaneously with immunosuppressants and cytostatics, the risk of developing leukopenia increases.

With the simultaneous use of opioid analgesics and anesthetics, the antihypertensive effect of enalapril is enhanced.

With the simultaneous use of loop diuretics and thiazide diuretics, the antihypertensive effect is enhanced. There is a risk of developing hypokalemia. Increased risk of renal dysfunction.

When used simultaneously with azathioprine, anemia may develop, which is due to inhibition of erythropoietin activity under the influence of ACE inhibitors and azathioprine.

A case of the development of an anaphylactic reaction and myocardial infarction with the use of allopurinol in a patient receiving enalapril is described.

Acetylsalicylic acid in high doses may reduce the antihypertensive effect of enalapril.

With the simultaneous use of beta-blockers, methyldopa, nitrates, calcium channel blockers, hydralazine, prazosin, the antihypertensive effect may be enhanced.

With the simultaneous use of insulin and hypoglycemic agents, sulfonylurea derivatives, hypoglycemia may develop.

With simultaneous use of ACE inhibitors and interleukin-3, there is a risk of developing arterial hypotension.

Syncope has been reported when used concomitantly with clozapine.