Certificate of conformity (COC) Enam, pills 10mg 20pcs

Enam, pills 10mg 20pcs

£7.0

Active ingredient:	Enalapril
Dosage form:	Pills
Indications for use:	Heart failure, Hypertension

Categories: Cardiovascular system, Hypertension, Medication

Description
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Composition

Each 2.5 mg,5 mg,10 mg and 20 mg tablet contains: Active ingredient: enalapril maleate 2.5 mg,5 mg,10 mg or 20 mg, respectively. Auxiliary substances: 2.5 mg and 5 mg tablets: lactose anhydrous, maleic acid, zinc stearate; tablets 10 mg and 20 mg: lactose anhydrous, zinc stearate.

Pharmacological action

Enam® is a drug that affects the renin-angiotensin-aldosterone system (RAAS) – ACE inhibitors. Enam® is used for the treatment of essential hypertension (primary arterial hypertension (AH)). any degree of severity and renovascular hypertension, both in monotherapy and in combination with other antihypertensive agents, in particular with diuretics. Enam® is also used to treat or prevent the development of heart failure (HF). Enam® is a derivative of two amino acids, L-alanine and L-proline. After oral use, enalapril is rapidly absorbed and hydrolyzed to enalaprilate, which is a highly specific and long-acting ACE inhibitor that does not contain a sulfhydryl group. ACE inhibitor (peptidyl-dipeptidase A) catalyzes the conversion of angiotensin I to the pressor peptide angiotensin II. After absorption, enalapril is hydrolyzed to enalaprilate, which inhibits ACE. ACE inhibition leads to a decrease in the concentration of angiotensin II in blood plasma, which leads to an increase in plasma renin activity (due to the elimination of negative feedback in response to renin release) and a decrease in aldosterone secretion. ACE is identical to the kininase II enzyme, so enalapril can also block the degradation of bradykinin, a peptide that has a pronounced vasodilating effect. The significance of this effect in the therapeutic effect of enalapril requires clarification. Despite the fact that the main mechanism by which enalapril reduces blood pressure (BP) is considered to be the suppression of RAAS activity, which plays an important role in regulating blood pressure, enalapril shows antihypertensive effects even in patients with hypertension and with reduced plasma renin activity. The use of enalapril in patients with hypertension leads to a decrease in blood pressure both in the “standing” and “lying” positions without a significant increase in heart rate (HR). Symptomatic postural hypotension develops infrequently. In some patients, achieving optimal BP reduction may require several weeks of therapy. Interruption of enalapril therapy does not cause a sharp rise in blood pressure. Effective ACE inhibition usually develops 2-4 hours after a single oral dose of enalapril. The antihypertensive effect develops within 1 hour, the maximum decrease in blood pressure is observed 4-6 hours after taking the drug. The duration of action depends on the dose. However, when using the recommended doses, the antihypertensive effect and hemodynamic effects persist for 24 hours. Antihypertensive therapy with enalapril leads to significant regression of left ventricular hypertrophy and preservation of its systolic function. In clinical hemodynamic studies in patients with essential hypertension, a decrease in blood pressure was accompanied by a decrease in total peripheral vascular resistance, an increase in cardiac output, and no changes or minor changes in heart rate. After taking enalapril, an increase in renal blood flow was observed. At the same time, the glomerular filtration rate (GFR) did not change, and there were no signs of sodium or fluid retention. However, in patients with initially reduced glomerular filtration rate, its rate usually increased. Long-term use of enalapril in patients with essential hypertension and renal insufficiency may lead to improved renal function, which is confirmed by an increase in GFR. In short clinical trials, patients with renal insufficiency and with or without diabetes mellitus after taking enalapril showed a decrease in albuminuria, renal excretion of IgG, and a decrease in total protein in the urine. With the simultaneous use of enalapril and thiazide diuretics, a more pronounced antihypertensive effect is observed. Enalapril reduces or prevents the development of hypokalemia caused by taking thiazides. Enalapril therapy is usually not associated with an undesirable effect on the concentration of uric acid in blood plasma. Enalapril therapy is accompanied by a favorable effect on the ratio of lipoprotein fractions in blood plasma and no effect or a favorable effect on the concentration of total cholesterol. In patients with HF treated with cardiac glycosides and diuretics, enalapril use caused a decrease in total peripheral resistance and blood pressure. Cardiac output increased, while heart rate (usually elevated in patients with HF) decreased. The pressure of jamming in the pulmonary capillaries also decreased. Exercise tolerance and heart failure severity, as assessed by the New York Heart Association (NYHA) criteria, improved. These effects were observed with long-term therapy. In patients with mild to moderate heart failure, enalapril slowed the progression of cardiac dilatation and heart failure, which was confirmed by a decrease in end-diastolic and systolic volumes of the left ventricle and an improvement in the left ventricular ejection fraction. Clinical data have shown that enalapril reduces the incidence of ventricular arrhythmias in patients with HF, although the main mechanisms and clinical significance of this effect are not known. Pharmacokinetics of absorption After oral use, enalapril is rapidly absorbed in the gastrointestinal tract. The maximum concentration of enalapril in the blood serum is reached within 1 hour after oral use. The degree of absorption of enalapril when taken orally is approximately 60%. Food intake does not affect the absorption of enalapril. After absorption, enalapril is rapidly hydrolyzed to form the active metabolite enalaprilate – a potent ACE inhibitor. The maximum concentration of enalaprilate in the blood serum is observed approximately 4 hours after ingestion of a dose of enalapril. The duration of absorption and hydrolysis of enalapril is similar for different recommended therapeutic doses. In healthy volunteers with normal renal function, the equilibrium concentration of enalaprilate in the blood serum is reached by day 4 from the start of enalapril use. Distribution in the therapeutic dose range, the binding of enalaprilate to plasma proteins does not exceed 60%. Metabolism There is no data on other significant pathways of enalapril metabolism other than hydrolysis to enalaprilate. Enalapril is excreted primarily through the kidneys. The main metabolites detected in the urine are enalaprilate, which accounts for approximately 40% of the dose, and unchanged enalapril (about 20%). The enalaprilate concentration curve in blood plasma has a long end phase, apparently due to its binding to ACE. The half-life of enalaprilat with a course of oral use of the drug is 11 hours. Pharmacokinetics in special patient groups Patients with impaired renal function The area under the concentration-time curve (AUC) of enalapril and enalaprilat increases in patients with renal insufficiency. In patients with mild to moderate renal insufficiency (creatinine clearance 40-60 ml/min), after taking enalapril at a dose of 5 mg once a day, the steady-state AUC of enalaprilat was approximately 2 times higher than in patients with unchanged renal function. In patients with severe renal insufficiency (creatinine clearance not exceeding 30 ml/min), the AUC value increased approximately 8-fold. The effective half-life of enalaprilat, after repeated use of enalapril in patients with severe renal insufficiency, increased and the onset of an equilibrium state of enalaprilat concentration was delayed (see the section “Dosage and use”). Enalaprilate can be removed from the general bloodstream by a hemodialysis procedure; the clearance during hemodialysis is 62 ml / min. Lactation After a single oral use of enalapril at a dose of 20 mg in postpartum patients, the average maximum concentration of enalapril in breast milk was 1.7 mcg/l (from 0.54 to 5.9 mcg/l) 4-6 hours after use. The average maximum concentration of enalaprilat was 1.7 mcg/l (from 1.2 to 2.3 mcg/L) and was observed at various times within 24 hours after use. Taking into account the data on maximum concentrations in breast milk, the estimated maximum intake of enalapril by a fully breastfed child is 0.16% of the dose calculated taking into account the mother’s body weight. In a woman who took enalapril orally at a dose of 10 mg once a day for%^%11 months, the maximum concentrations of enalapril in breast milk were 2 mcg/l 4 hours after use, the maximum concentrations of enalaprilat were 0.75 mcg/l approximately 9 hours after use. The average concentration in breast milk within 24 hours after taking enalapril was 1.44 mcg/l and enalaprilat-0.63 mcg/l. In one woman who took enalapril 5 mg once and in two women who took enalapril 10 mg once, the concentration of enalaprilate in breast milk was below the detectable level (less than 0.2 mcg/l) 4 hours after use. The concentration of enalapril in them was not determined.

Indications

Essential hypertension of any severity. Renovascular hypertension. Heart failure of any severity. Enam® is also indicated for the treatment of patients with clinical signs of HF. :

improving patient survival;
slowing the progression of HF;
reducing the frequency of hospitalizations for HF.

Prevention of the development of clinically expressed heart failure. In patients without clinical symptoms of HF with left ventricular dysfunction, Enam® is indicated for: :

slowing the development of clinical manifestations of HF;
reducing the frequency of hospitalizations for HF.

Prevention of coronary ischemia in patients with left ventricular dysfunction. Enam® is indicated for:

reducing the incidence of myocardial infarction;
reducing the frequency of hospitalizations for unstable angina.

Use during pregnancy and lactation

The use of Enam® during pregnancy is not recommended. If pregnancy is diagnosed, Enam® should be discontinued immediately, unless the drug is considered vital for the mother. In the published results of a retrospective epidemiological study of newborns whose mothers took ACE inhibitors during the first trimester of pregnancy, there was an increased risk of developing serious congenital malformations, compared with newborns whose mothers did not take ACE inhibitors during the first trimester of pregnancy. The number of cases of birth defects was low, and the results of this study were not re-confirmed. ACE inhibitors can cause disease or death of the fetus or newborn when used by pregnant women during the second and third trimesters of pregnancy. The use of ACE inhibitors during these periods was accompanied by negative effects on the fetus and newborn, which manifested itself in the form of arterial hypotension, renal failure, hyperkalemia and/or hypoplasia of the skull bones in the newborn. Preterm birth, delayed fetal development, and non-closure of the ductus arteriosus have also been reported, but it is unclear whether these cases were related to the action of ACE inhibitors. Perhaps the development of oligohydramnion occurs due to a decrease in fetal kidney function. This complication can lead to contracture of the extremities, deformity of the skull bones, including its facial part, and hypoplasia of the fetal lungs. When prescribing Enam® during pregnancy, the patient should be informed about the potential risk to the fetus. These undesirable effects on the embryo and fetus do not appear to be the result of intrauterine action of ACE inhibitors during the first trimester of pregnancy. In 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. In case of detection of oligohydramnion during ultrasound examination, it is necessary to stop taking Enam®, unless taking the drug is considered vital for the mother. However, both the patient and the doctor should be aware that oligohydramnion develops when the fetus is permanently damaged. If ACE inhibitors are used during pregnancy and oligohydramnion develops, then depending on the week of pregnancy, a stress test, a non-stress test, or a biophysical profile of the fetus may be necessary to assess the functional state of the fetus. Newborns whose mothers have taken Enam® during pregnancy should be carefully evaluated for hypotension, oliguria, and hyperkalemia. When developing oliguria, special attention should be paid to maintaining blood pressure and renal perfusion. Enalapril penetrates the placental barrier. It can be partially removed from the newborn’s circulation by peritoneal dialysis. In theory, it can also be removed through an exchange blood transfusion. Enalapril and enalaprilat are excreted in the mother’s breast milk in trace amounts. If it is necessary to use the drug during breastfeeding, the patient should stop breastfeeding.

Contraindications

Hypersensitivity to any of the components of the drug. A history of angioedema associated with the use of ACE inhibitors, as well as hereditary or idiopathic angioedema. Concomitant use with aliskiren and drugs containing aliskiren in patients with diabetes mellitus and / or moderate to severe renal impairment (GFR less than 60 ml / min/1.73 m2 of body surface area) [see section “Interaction with other drugs”]. Concomitant use with angiotensin II receptor antagonists in patients with diabetic nephropathy. Age up to 18 years (efficacy and safety have not been established). Pregnancy and breast-feeding period. Hereditary problems of lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome. With caution:Bilateral renal artery stenosis or stenosis of the artery of a single kidney; conditions after kidney transplantation; aortic or mitral stenosis; hypertrophic obstructive cardiomyopathy;ischemic heart disease or cerebrovascular diseases; renal failure; renovascular hypertension; suppression of bone marrow hematopoiesis; systemic connective tissue diseases (systemic lupus erythematosus, scleroderma, etc. ), immunosuppressive therapy, treatment with allopurinol or procainamide or a combination of these complicating factors; liver failure; diabetes mellitus; hyperkalemia; when used concomitantly with potassium-sparing diuretics, potassium preparations, potassium-containing substitutes for table salt and lithium preparations; during the procedure of low-density lipoprotein apheresis (LDL apheresis) using dextran sulfate; burdened allergic anamnesis or angioedema in the anamnesis;conditions accompanied by a decrease in the volume of circulating blood (including diuretic therapy, diet with restriction of table salt, dialysis, diarrhea or vomiting); during desensitization with an allergen from hymenopteran venom; in patients undergoing dialysis using high-flow membranes (such as AN 69®);in patients after major surgical interventions or during general anesthesia; in patients of the black race.

Side effects

Enam® is generally well tolerated. In clinical trials, the cumulative incidence of adverse events with enalapril did not exceed that with placebo. In most cases, the adverse events were mild, transient, and did not require discontinuation of therapy. When using enalapril, the following adverse events were observed (very often: ≥ 10%, often: ≥ 1% and < 10%, infrequently: ≥ 0.1% and < 1%, rarely ≥ 0.01% and < 0.1%, very rarely: :Blood and lymphatic system disorders often: anemia (including aplastic and hemolytic). Rare: neutropenia, decreased hemoglobin, decreased hematocrit, thrombocytopenia, agranulocytosis, bone marrow suppression, pancytopenia, lymphadenopathy, autoimmune diseases. Disorders of the endocrine system Frequency unknown: syndrome of inadequate secretion of antidiuretic hormone. Metabolic and nutritional disorders often: hypoglycemia (see section “Special instructions”). Nervous system disorders and mental disorders often: headache, depression. Infrequently: confusion, drowsiness, insomnia, increased nervousness, paresthesia, systemic dizziness. Rare: unusual dreams, sleep disturbances. Visual disturbances are very common: blurred vision. Disorders of the heart and blood vessels very often: dizziness. Often: marked decrease in blood pressure, fainting, chest pain, arrhythmia, angina pectoris, tachycardia. Infrequently: orthostatic hypotension, palpitation, myocardial infarction or stroke*, possibly secondary to severe hypotension in high-risk patients (see section “Special instructions”). Rare: Raynaud’s syndrome. * The frequency of cases was comparable to that observed in clinical trials when taking placebo or another comparison drug. Respiratory, thoracic and mediastinal disorders Very common: cough. Often: shortness of breath. Infrequently: rhinorrhea, sore throat, hoarseness of voice, bronchospasm/bronchial asthma. Rare: pulmonary infiltrates, rhinitis, allergic alveolitis/eosinophilic pneumonia. Digestive system disorders Very common: nausea. Common: diarrhea, abdominal pain, taste problems. Infrequently: intestinal obstruction, pancreatitis, vomiting, dyspepsia, constipation, anorexia, stomach irritation, dry oral mucosa, stomach and duodenal ulcers. Rare: stomatitis/aphthous ulcers, glossitis. Very rare: intestinal edema. Liver and biliary tract disorders Rarely: liver failure, hepatitis (hepatocellular or cholestatic), hepatitis (including necrosis), cholestasis (including jaundice). Skin and subcutaneous tissue disorders Often: skin rash, hypersensitivity reactions/angioedema: angioedema of the face, extremities, lips, tongue, vocal folds and / or larynx (see section “Special instructions”). Infrequently: increased sweating, pruritus, urticaria, alopecia. Rare: erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, pemphigus, erythroderma. A symptom complex has been reported that may include all or some of the following symptoms:fever, serositis, vasculitis, myalgia/myositis, arthralgia/arthritis, positive antinuclear antibody test, increased erythrocyte sedimentation rate (ESR), eosinophilia and leukocytosis. Skin rash, photosensitization, and other skin reactions may also occur. Renal and urinary tract disorders often: impaired renal function, renal failure, proteinuria. Rare: oliguria. Disorders of the genitals and mammary gland often: erectile dysfunction. Rare: gynecomastia.Common disorders very common: asthenia. Often: increased fatigue. Infrequently: muscle cramps, “flushes” of blood to the skin of the face, tinnitus, discomfort, fever. Laboratory and instrumental data often: hyperkalemia, increased serum creatinine concentration. Infrequently: increased blood urea concentration, hyponatremia. Rarely: increased activity of “hepatic” transaminases, increased concentration of bilirubin in the blood serum. The following adverse events were identified during post-marketing surveillance, but no causal relationship with enalapril was established: urinary tract infection, upper respiratory tract infection, bronchitis, cardiac arrest, atrial fibrillation, herpes zoster, melena, ataxia, pulmonary embolism and pulmonary infarction, hemolytic anemia, including cases of hemolysis in patients with glucose-6 deficiency-phosphate dehydrogenase.

Interaction

When Enam is co-administered with NSAIDs, the hypotensive effect of enalapril may decrease;

with potassium-sparing diuretics (spironolactone, triamterene, amiloride), hyperkalemia may develop;

with lithium salts, lithium excretion may slow down (monitoring of lithium concentration in blood plasma is shown). Ethanol enhances the antihypertensive effect of the drug. When used concomitantly with antipyretics and analgesics, the effectiveness of Enam may decrease. Enalapril weakens the effect of drugs containing theophylline.

Cimetidine prolongs the action of enalapril.

Concomitant use with diuretics, beta-blockers, methyldopa, nitrates, calcium channel blockers, hydralazine, prazosin increases the hypotensive effect of enalapril.

The use of Enam together with anesthesia agents that have an antihypertensive effect may cause arterial hypotension.

How to take, course of use and dosage

Enam® is taken orally, regardless of food intake. Essential hypertension The initial dose is 10-20 mg once a day, depending on the severity of hypertension. For mild hypertension, the recommended starting dose is 10 mg once a day. With other degrees of hypertension, the initial dose is 20 mg once a day. The maintenance dose is 1 tablet of 20 mg once a day. The dosage is selected individually for each patient, but the maximum dose should not exceed 40 mg / day, which is taken once or divided into 2 doses, depending on the patient’s tolerance of the drug. Renovascular hypertension Since patients in this group may have particularly sensitive blood pressure and renal function to ACE inhibition, therapy is initiated with a low initial dose of 5 mg or less. The dose is then adjusted according to the patient’s needs and condition. Usually, the effective dose of Enam® is 20 mg once a day when taken daily. Caution should be exercised when using Enam® in patients who have recently taken diuretics (see “Concomitant treatment of hypertension with diuretics” below). Dosage with concomitant treatment of hypertension with diuretics, symptomatic hypotension may develop after the first use of Enam®. This effect is most likely in patients who take diuretics. The drug is recommended to be used with caution, as these patients may have a violation of the water-electrolyte balance. Diuretics should be discontinued 2-3 days prior to the start of Enam therapy. If this is not possible, then the initial dose of Enam® should be reduced (to 5 mg or less) to determine the primary effect of the drug on blood pressure. Further, the dosage should be selected taking into account the needs and condition of the patient. Dosage in patients with renal insufficiency, the interval between doses of Enam® should be increased and / or the dose should be reduced. Creatinine clearance, ml / min Initial dose, mg / day<80 >30 ml / min 5-10 mg<80 >< or =30 >10 ml / min 2.5 mg< or =30 >** Enalapril is undergoing dialysis. Dose adjustment on days when dialysis is not performed should be carried out depending on the level of blood pressure. Heart failure/asymptomatic left ventricular dysfunctionthe initial dose of Enam® in patients with clinically significant HF or asymptomatic left ventricular dysfunction is 2.5 mg. At the same time, the use of the drug should be carried out under careful medical supervision to determine the primary effect of the drug on blood pressure. Enam® can be used for the treatment of HF with severe clinical manifestations, usually in combination with diuretics and, when necessary, with cardiac glycosides. In the absence of symptomatic hypotension (resulting from treatment with Enam®) or after its correction, the dose of the drug should be gradually increased to the usual maintenance dose of 20 mg, which is taken either once or divided into 2 doses, depending on the patient’s tolerance to the drug. Dose adjustment can be made within 2-4 weeks or in a shorter time if there are residual signs and symptoms of HF. This therapeutic regimen effectively reduces the mortality rates of patients with clinically significant HF. Both before and after starting treatment with Enam®, regular monitoring of blood pressure and renal function should be carried out (see the section “Special Instructions”), since hypotension has been reported as a result of taking the drug, followed (more rarely) by acute renal failure. In patients taking diuretics, the dose of diuretics should be reduced if possible before starting treatment with Enam®. The development of arterial hypotension after taking the first dose of Enam® does not mean that arterial hypotension will develop again with long-term treatment, and does not indicate the need to stop taking the drug. Serum potassium levels should also be monitored during treatment with Enam® (see section “Interactions with other medicinal products”).

Overdose

Symptoms: arterial hypotension.

Treatment: you should put the patient down, raise your legs. In mild cases of overdose, the patient is prescribed a saline solution inside.

In more serious cases, measures aimed at stabilizing blood pressure are carried out in a hospital, and saline or plasma substitutes are administered intravenously.

Possible use of hemodialysis.

Special instructions

Symptomatic arterial hypotensionsymptomatic arterial hypotension is rarely observed in patients with uncomplicated hypertension. In patients with hypertension taking enalapril, hypotension develops more often against the background of dehydration, which occurs, for example, as a result of diuretic therapy, restriction of table salt intake, in patients on dialysis, as well as in patients with diarrhea or vomiting (see the sections “Side effects”; “Interaction with other drugs”). Symptomatic hypotension was also observed in patients with HF with or without renal insufficiency. Hypotension occurs more frequently in patients with more severe HF, hyponatremia, or impaired renal function, who are treated with higher doses of loop diuretics. In these patients, treatment with Enam® should be initiated under medical supervision, which should be especially careful when changing the dose of Enam® and / or a diuretic. Similarly, patients with ischemic heart disease or cerebrovascular diseases should be monitored, in which an excessive decrease in blood pressure can lead to the development of myocardial infarction or stroke. If arterial hypotension develops, the patient should be laid down and, if necessary, a 0.9% sodium chloride solution should be administered. Transient arterial hypotension when taking Enam® is not a contraindication to further use and an increase in the dose of the drug, which can be continued after filling the volume of fluid and normalization of blood pressure. In some patients with HF and with normal or reduced blood pressure, Enam® may cause an additional decrease in blood pressure. This reaction to taking the drug is expected and is not a reason to stop treatment. In cases where hypotension is stable, the dose should be reduced and/or treatment with a diuretic and / or Enam®should be discontinued. Aortic or mitral stenosis / hypertrophic obstructive cardiomyopathyas all drugs with vasodilating effects, ACE inhibitors should be used with caution in patients with obstruction of the outflow pathway from the left ventricle. Impaired renal function in some patients, hypotension that develops after starting treatment with ACE inhibitors may lead to further deterioration of renal function. Acute renal failure, usually reversible, has been reported in some cases. In patients with renal insufficiency, it may be necessary to reduce the dose and / or frequency of taking the drug (see the section “Dosage and use”). Some patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney experienced an increase in the concentration of urea in the blood and serum creatinine. The changes were usually reversible, and the indicators returned to their original values after discontinuation of treatment. This type of change is most likely to occur in patients with renal insufficiency. In some patients who did not develop kidney disease prior to treatment, Enam® in combination with diuretics usually caused a slight and transient increase in the concentration of urea in the blood and serum creatinine. In such cases, it may be necessary to reduce the dose and/or discontinue the diuretic and / or Enam®. Kidney transplantation There is no experience of use in patients after kidney transplantation, so treatment with Enam® is not recommended in patients after kidney transplantation. Hepatic insufficiency The use of ACE inhibitors has rarely been associated with the development of a syndrome that begins with cholestatic jaundice or hepatitis and progresses to fulminant liver necrosis, sometimes with a fatal outcome. The mechanism of this syndrome has not been studied. If jaundice occurs or there is a significant increase in the activity of” hepatic ” transaminases, against the background of the use of ACE inhibitors, the drug should be discontinued and appropriate auxiliary therapy should be prescribed; the patient should be under appropriate supervision. Neutropenia/Agranulocytosis Neutropenia/agranulocytosis, thrombocytopenia and anemia have been observed in patients taking ACE inhibitors. Neutropenia is rare in patients with normal renal function and no other complicating factors. Enalapril should be used with extreme caution in patients with systemic connective tissue diseases (systemic lupus erythematosus, scleroderma, etc. ), taking immunosuppressive therapy, allopurinol or procainamide, or a combination of these complicating factors, especially if there are already existing renal dysfunction. Some of these patients developed serious infectious diseases, which in some cases did not respond to intensive antibiotic therapy. If enalapril is used in these patients, regular monitoring of the number of white blood cells and lymphocytes in the blood is recommended, and patients should be warned to report any signs of infectious disease. Hypersensitivity reactions / angioedema When using ACE inhibitors, including Enam®, there have been rare cases of angioedema of the face, limbs, lips, tongue, vocal folds and / or larynx that occurred during different periods of treatment. In very rare cases, the development of intestinal edema has been reported. In such cases, you should immediately stop taking Enam® and carefully monitor the patient’s condition in order to control and correct clinical symptoms. Even in cases where only tongue edema is observed without the development of respiratory distress syndrome, patients may need long-term follow-up, since antihistamines and corticosteroids may not be sufficient. Very rarely, death has been reported due to angioedema associated with laryngeal edema or tongue edema. Swelling of the tongue, vocal folds, or larynx can lead to airway obstruction, especially in patients who have undergone respiratory surgery. In cases where edema is localized in the tongue, vocal folds or larynx and can cause airway obstruction, appropriate treatment should be immediately prescribed, which may include subcutaneous use of 0.1% epinephrine (epinephrine) solution (0.3-0.5 ml) and/or ensure airway patency. Angioedema was observed more frequently in black patients treated with ACE inhibitors than in patients of other races. Patients with a history of angioedema not associated with ACE inhibitors may be more at risk of developing angioedema with ACE inhibitor therapy (see section “Contraindications”). Patients taking concomitant ACE inhibitors and mTOR inhibitors, gliptins, racecadotril, or estramustine had an increased risk of developing angioedema. Anaphylactoid reactions during desensitization with an allergen from hymenopteran venomin rare cases, patients taking ACE inhibitors developed life-threatening anaphylactoid reactions during desensitization with an allergen from hymenopteran venom. Adverse reactions can be avoided if the ACE inhibitor is temporarily discontinued prior to desensitization. Anaphylactoid reactions during LDL apheresis In patients taking ACE inhibitors during LDL apheresis using dextran sulfate, life-threatening anaphylactoid reactions were rarely observed. These reactions can be avoided if the ACE inhibitor is temporarily discontinued prior to each LDL apheresis procedure. Patients undergoing hemodialysis anaphylactoid reactions have been observed in patients undergoing dialysis using high-flow membranes (such as AN 69®) and simultaneously receiving ACE inhibitor therapy. Dialysis membranes of a different type or antihypertensive agents of other classes should be used in these patients. Coughing There have been cases of coughing during therapy with ACE inhibitors. As a rule, the cough is unproductive, permanent and stops after discontinuation of therapy. Cough associated with the use of ACE inhibitors should be considered in the differential diagnosis of cough. Surgical interventions/General anaesthetistsin large surgical procedures or general anaesthesia with antihypertensive agents, enalaprilate blocks the formation of angiotensin II caused by the compensatory release of renin. If a marked decrease in blood pressure occurs due to such a mechanism, it can be corrected by increasing the volume of circulating blood. Hyperkalemia (see section “Interaction with other drugs”)The risk of developing hyperkalemia is observed with renal failure, diabetes mellitus, as well as with the simultaneous use of potassium-sparing diuretics (for example, spironolactone, eplerenone, triamterene or amiloride), potassium supplements or potassium-containing salts, drugs containing co-trimoxazole. The use of potassium supplements, potassium-sparing diuretics, or potassium-containing salts, especially in patients with impaired renal function, can lead to a significant increase in serum potassium. Hyperkalemia can lead to serious, sometimes fatal, arrhythmias. If the concomitant use of Enam® and the drugs listed above is necessary, caution should be exercised and the serum potassium content should be regularly monitored. Hypoglycemia Patients with diabetes mellitus taking oral hypoglycemic agents or insulin should be informed about the need for regular monitoring of blood glucose concentrations (hypoglycemia) before starting the use of ACE inhibitors, especially during the first month of simultaneous use of these drugs (see the section “Interaction with other drugs”). Lithium preparations Concomitant use of lithium and enalapril is not recommended (see section “Interaction with other medicinal products”). Dual blockade of the renin-angiotensin-aldosterone system hypotension, syncope, stroke, hyperkalemia, and impaired renal function (including acute renal failure) have been reported in susceptible patients, especially when combined therapy with drugs that affect the RAAS is used (see section “Interaction with other drugs”). Concomitant use of Enam® with aliskiren or aliskiren-containing drugs in patients with diabetes mellitus and/or moderate or severe renal insufficiency (GFR less than 60 ml/min / 1.73 m2 of body surface area) is contraindicated and is not recommended in other patients. Concomitant use of Enam® with ARA II in patients with diabetic nephropathy is contraindicated and is not recommended in other patients (see section “Contraindications”). Use in elderly patients Clinical studies on the efficacy and safety of enalapril were similar in older and younger patients with hypertension. As with other ACE inhibitors, enalapril appears to be less effective in reducing blood pressure in black patients than in patients of other races, which may be due to the higher prevalence of conditions with low plasma renin activity in the population of black patients with hypertension. The effect of Enam® on the ability to drive vehicles and work with mechanisms has not been studied. However, some adverse events (such as dizziness) that have been observed while taking Enam® may affect the ability to drive vehicles and work with mechanisms (see the section “Side effects”).