Index of drugs

Treatment of hypertension. Treatment of symptomatic heart failure. Prevention of symptomatic heart failure in patients with asymptomatic left ventricular dysfunction (left ventricular dysfunction) (ejection fraction ≤ 35%).

1 tabl contains 5 mg, 10 mg or 20 mg of Enalapril maleate. The tablets contain lactose.

Angiotensin converting enzyme inhibitor. Enalapril maleate is a prodrug, the active form of which is a metabolite, enalaprilat. It lowers blood pressure by acting on the renin-angiotensin-aldosterone system. In hypertensive patients, enalapril causes hypotension in the supine and standing position without compensatory increase in cardiac function. In patients with heart failure, it decreases peripheral resistance, arterial pressure, increase in minute capacity at reduced heart rate. About 60% of the administered dose of the drug is absorbed from the gastrointestinal tract. Food does not affect the absorption of enalapril. Maximum reduction of blood pressure is observed 4-6 h after drug administration. Enalaprilat is approximately 60% bound to plasma proteins. Approx. 60% of the administered dose (enalapril maleate) is excreted in the urine (40% as enalaprilat and 20% as enalapril). T_0,5 is about 11 hours. The concentration of enalapril and enalaprilat is increased in patients with renal insufficiency. The drug can be removed from the blood by hemodialysis.

Hypersensitivity to Enalapril, other ACE inhibitors or any of the excipients. History of angioneurotic edema associated with previous treatment with ACE inhibitors. Hereditary or idiopathic angioneurotic edema. II and III trimester of pregnancy. Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (glomerular filtration rate, GFR <60 ml / min / 1.73 m²).

Caution in patients at risk of hypotension: in patients with fluid deficiency (caused by, for example, diuretic therapy, salt restricted diet, dialysis, and diarrhea or vomiting), heart failure with or without co-existing renal failure, ischemic heart disease or disease cerebral vessels. The risk of symptomatic hypotension is higher in patients with more severe heart failure, using high doses of loop diuretics, in hyponatremia or renal dysfunction. In patients with an increased risk of symptomatic hypotension, treatment should be initiated under close medical supervision and should be closely monitored during each change of the dose of enalapril and / or diuretic. If possible, it is recommended to temporarily discontinue the use of a diuretic. Transient hypotension is not a contraindication to the administration of subsequent doses of the drug after normalizing blood pressure by increasing the volume of fluids. If signs of hypotension occur, it may be necessary to reduce the dose or discontinue diuretic and / or enarenal. Caution should be exercised when using the drug in patients with aortic stenosis or other narrowing of the left ventricular outflow tract. Do not use the drug in the case of cardiogenic shock and hemodynamically significant stenosis. Carefully used in patients with impaired renal function, these patients should be regularly monitored for potassium and creatinine in the plasma. Renal failure has been reported with the use of enalapril, especially in patients with severe heart failure or pre-existing kidney disease, including renal artery stenosis. In some hypertensive patients with no previous known renal disease, increases in urea and creatinine in the blood have been seen if enalapril has been given with a diuretic. It may be necessary to reduce the dose of the preparation and / or discontinue diuretic use. In this case, there is an increased probability of renal artery stenosis.In patients with renovascular hypertension with bilateral renal artery stenosis or renal artery stenosis of one kidney, treatment should be started under strict control, from very small doses, very carefully increase the dose and control renal function (risk of hypotension and renal failure). There is no experience in the use of enalapril in patients after recent kidney transplantation, therefore the use of this preparation is not recommended in these patients. In patients treated with ACE inhibitors who develop jaundice or markedly elevated liver enzymes, ACE inhibitors should be discontinued. Use with extreme caution in patients with vascular collagen, receiving immunosuppressants, Allopurinol or procainamide, or if these factors coexist, especially when pre-existing renal impairment has occurred - periodic monitoring of white blood cell counts is recommended and patients should be advised to report any symptoms infection. Some of the patients in this group developed severe infections, which in rare cases did not respond to intensive antibiotic treatment. There have been reports of angioneurotic edema of the face, limbs, lips, tongue, glottis and / or larynx in patients treated with ACE inhibitors. Angioedema may occur at any time during treatment. If it occurs, the enalapril should be discontinued immediately and the patient monitored accordingly until the symptoms disappear. Angioedema is more common in black patients using ACE inhibitors than in other breeds. In patients with a history of angioneurotic edema, unrelated to treatment with an ACE inhibitor, there is an increased risk of developing angioneurotic edema when using an ACE inhibitor. During LDL apheresis with dextran sulphate and during Hymenoptera venom deseaction, anaphylactoid reactions may occur, they can be avoided by temporarily stopping the use of ACE inhibitors before each apheresis and before each desensitization. In patients treated with ACE inhibitors who undergo dialysis with high permeability membranes (eg AN 69), consideration should be given to using a different type of dialysis membrane or an anti-hypertensive drug from another group (risk of anaphylactoid reactions). In patients undergoing surgery or anesthesia with hypotensive agents, enalapril inhibits the production of angiotensin II in response to compensatory renin excretion. Hypotension caused by this mechanism can be corrected by increasing the volume of circulating blood. Caution (risk of hyperkalemia) in patients with renal insufficiency, decreased renal function,> 70 years, diabetes, concomitant disorders, especially dehydration, acute decompensated heart failure, metabolic acidosis or patients receiving concomitant potassium sparing diuretics, potassium supplements or salt substitutes Potassium containing potassium, as well as patients taking other medicines that increase serum potassium (eg heparin). If it is necessary to use these preparations concomitantly, caution should be used and frequently the serum potassium level should be measured. The use of lithium salts simultaneously with enalapril is not recommended. In patients with diabetes who are being treated with oral antidiabetic agents or insulin and who are started on an ACE inhibitor, blood Glucose should be closely monitored, especially during the first month of combination therapy. Experience with efficacy and safety in children> 6 years of hypertension is limited, but lack of experience with the use of the drug in other indications. There are very few data on pharmacokinetics in children> 2 months of age. The use is not recommended in children for indications other than hypertension. Due to the lack of relevant data, the drug is not recommended for newborns and children and adolescents with a glomerular filtration rate (GFR) <30 ml / min / 1.73 m². The concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of hypotension, hyperkalaemia and renal dysfunction (including acute renal failure) - therefore, dual blocking of the RAA system is not recommended by concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren. If the use of a dual RAA blockade is absolutely necessary, it should only be carried out under the supervision of a specialist, and the vital parameters of the patient, such as kidney function, electrolyte concentration and blood pressure should be closely monitored.In patients with diabetic nephropathy, ACE inhibitors and angiotensin II receptor antagonists should not be used concurrently. The product contains lactose - should not be used in patients with rare hereditary galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose. This medicine is less effective in lowering blood pressure in black patients.

The use of the preparation in the first trimester of pregnancy is not recommended (there is a risk of teratogenic effect). Use in the second and third trimester of pregnancy is contraindicated. Enalapril used in the second and third trimester of pregnancy is toxic to fetal development (deterioration of renal function, oligohydramnios, delayed ossification of the skull) and newborn (renal failure, hypotension, hyperkalemia) - when exposure to the drug occurred from the second trimester of pregnancy, Ultrasound of the skull and kidneys is recommended; newborns whose mothers have taken ACE inhibitors should be closely monitored because of the possibility of hypotension. The concentration of enalapril in breast milk is very low. Although these concentrations appear to be of little clinical relevance, the formulation is not recommended during breastfeeding of premature babies and newborns for the first few weeks of life due to potential cardiovascular and kidney effects and insufficient clinical experience. For older infants, the use of enelapril during breastfeeding may be considered if treatment is necessary for the mother and the child is observed for side effects.

Very often: blurred vision, dizziness, cough, nausea, weakness. Common: headaches, depression, hypotension (including orthostatic hypotension), syncope, chest pain, arrhythmia, angina pectoris, tachycardia, dyspnea, diarrhea, abdominal pain, taste disturbances, rash, hypersensitivity reactions / angioneurotic edema ( angioneurotic edema of the face, limbs, lips, tongue, glottis and / or larynx), fatigue, hyperkalemia, increase in serum creatinine. Uncommon: anemia (including aplastic and hemolytic anemia), hypoglycaemia, confusion, drowsiness, insomnia, nervousness, paresthesia, peripheral vertigo, palpitations, myocardial infarction or cerebrovascular incident (probably secondary to excessive reduction of blood pressure high-risk patients), nasal discharge, sore throat and hoarseness, bronchospasm / asthma, intestinal obstruction, pancreatitis, vomiting, indigestion, constipation, lack of appetite, gastric irritation, dry mouth, peptic ulcer, excessive sweating , pruritus, urticaria, hair loss, kidney problems, kidney failure, proteinuria, impotence, muscle cramps, facial flushing, tinnitus, malaise, fever, increased blood urea, hyponatremia. Rare: neutropenia, decreased hemoglobin, hematocrit reduction, thrombocytopenia, agranulocytosis, bone marrow suppression, pancytopenia, generalized enlargement of lymph nodes, autoimmune diseases, unusual dreams, sleep disorders, Raynaud's phenomenon, lung infiltration, rhinitis, allergic alveolitis / eosinophilic pneumonia, stomatitis / inflammation of the mouth, inflammation of the tongue, liver failure, hepatitis (hepatocellular or cholestatic), hepatitis (including necrosis), cholestasis (including jaundice), erythema multiforme, Stevens syndrome -Johnson, exfoliative dermatitis, toxic epidermal necrolysis, pemphigus, erythroderma, oliguria, gynecomastia, increase in liver enzymes, increase in serum bilirubin. Very rare: angioedema of the intestines. Not known: syndrome of abnormal secretion of antidiuretic hormone (SIADH). A kit is also described that may include some or all of the following symptoms: fever, polyserositis, vasculitis, muscle pain / inflammation, joint pain / arthritis, positive antinuclear antibody titres, increased ESR, eosinophilia and leukocytosis. Rash, hypersensitivity to light and other skin symptoms may occur.In rare cases, the use of ACE inhibitors has been associated with a syndrome that starts with cholestasis jaundice or hepatitis and progresses to fulminant hepatic necrosis and (sometimes) to death.

Orally.Adults. Hypertension: the starting dose is 5-20 mg once a day, depending on the degree of hypertension and the patient's condition. In mild hypertension, the recommended dose is 5-10 mg once a day. Patients who have increased activity of the renin-angiotensin-aldosterone system (eg patients with renovascular hypertension, salt and / or fluid deficiency, decompensated heart failure or severe hypertension) may experience an aggravated decrease in blood pressure after the initial dose. In these patients, a starting dose of 5 mg or less is recommended, and treatment should be started under the supervision of a physician. In patients previously using high doses of diuretics, hypotension may occur at the beginning of treatment with enalapril. In these patients an initial dose of 5 mg or less is recommended. If possible, use diuretic treatment 2-3 days before starting treatment. Renal function and serum potassium should be monitored. The usual maintenance dose is 20 mg per day. The maximum maintenance dose is 40 mg per day.Heart failure / asymptomatic abnormalities (dysfunction) of the left ventricle. In the treatment of symptomatic heart failure, the drug is used in combination with diuretics and, if necessary, with digitalis glycosides or beta-blockers. The initial dose is 2.5 mg and should be given under close medical supervision to determine the effect on blood pressure at the beginning of treatment. If symptomatic hypotension does not occur after initiation of treatment for heart failure or if it has been compensated, the dose should be increased gradually to the usual maintenance dose of 20 mg, given as a single dose or 2 divided doses, depending on the patient's tolerability. Adjustment of the maintenance dose should take place in the period of 2-4 weeks. The maximum dose is 40 mg per day in 2 doses. Week 1: 1.-3. day: 2.5 mg / day in a single dose (caution should be exercised in patients with impaired renal function or diuretic therapy); 4-7. day: 5 mg / day in 2 divided doses. Week 2: 10 mg / day in a single dose or in 2 divided doses. Week 3 and 4: 20 mg / day in a single dose or two divided doses. Before starting treatment and during treatment, blood pressure and renal function should be checked. Before starting treatment, it is recommended to reduce the dose of diuretics used, if possible. The occurrence of hypotension after the first dose does not mean that it occurs again during chronic use and does not preclude the continued use of this drug. In this case, the concentration of potassium in the serum and renal function should also be monitored. In patients with renal insufficiency, the interval between consecutive doses should be prolonged and / or the dose reduced: 30 Children and youth. For children who can swallow the tablets, the dose should be determined individually depending on the patient's condition and blood pressure values. The recommended starting dose for children at from 20 kg to <50 kg is 2.5 mg once a day, and in patients with a body weight> 50 kg - 5 mg once a day. Depending on the needs, the dose can be increased up to a maximum of 20 mg per day in patients with bw. from 20 kg to <50 kg and 40 mg in patients with an ≥50 kg. Enalapril is not recommended for newborns and children and adolescents with glomerular filtration rate (GFR) <30 ml / min / 1.73 m².