Index of drugs

Hypertension. Symptomatic heart failure. Prevention of symptomatic heart failure in patients with left ventricular dysfunction (with ejection fraction <35%).

1 tabl contains 5 mg, 10 mg or 20 mg of Enalapril maleate.

Angiotensin converting enzyme inhibitor. Enalapril maleate is a prodrug, the active form of which is a long-acting 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. Maximum reduction of blood pressure is observed 4-6 h after drug administration. It binds to plasma proteins in about 60%. It is metabolised in the liver and excreted mainly in the urine (60%). 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 the drug, to any other component of the preparation or to any other ACE inhibitor. 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).

Use with caution, because of the risk of hypotension, which is greater in patients with water-electrolyte imbalance (caused by, for example, diuretic therapy, diet with salt restriction, dialysis and diarrhea or vomiting), heart failure, with or without co-existing renal failure and ischemic heart disease or cerebrovascular disease. In patients with an increased risk of symptomatic hypotension, treatment should be initiated under the close supervision of a physician and strict control should be ensured at each change in dosage of enalapril and / or diuretic. Transient hypotension is not a contraindication to the administration of subsequent doses of the drug after achieving normalization of blood pressure by increasing the volume of fluids. If signs of hypotension occur, it may be necessary to reduce the dose and / or discontinue diuretic and / or enalapril. 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 haemodynamically significant stenosis and in patients with recent kidney transplantation, due to lack of experience in the use. 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. In patients treated with ACE inhibitors who develop jaundice or markedly elevated liver enzymes and angioneurotic edema of the face, limbs, lips, glottis, and / or larynx, ACE inhibitors should be discontinued and appropriate treatment initiated. Use with extreme caution in patients with collagen vascular disease receiving immunosuppressive drugs, Allopurinol or procainamide, or if these factors coexist, especially when pre-existing renal dysfunction has occurred; if the drug is used in these patients, it is recommended to periodically check the number of white blood cells. Anaphylactoid reactions during LDL apheresis can be avoided by temporarily stopping the use of ACE inhibitors before each apheresis.Do not use the preparation in patients treated with ACE-inhibitors dialyzed with high-flow membranes who have more frequent anaphylactic reactions or consider using other types of dialysis membranes when dialysis or other type of antihypertensive drug is required. Anaphylactoid reactions during desensitization of hymenoptera venom can be avoided by early discontinuation of ACE inhibitors before desensitization. In patients undergoing major surgery or anesthetized with agents that cause hypotension, the drug 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. Diabetic patients treated with oral antidiabetic agents or insulin who start treatment with an ACE inhibitor should be advised that frequent monitoring of blood Glucose is required, particularly during the first month of treatment. Use with caution for hyperkalaemia in patients with co-existing renal insufficiency, diabetes mellitus or in patients receiving concomitant potassium-sparing diuretics (eg spironolactone, triamterene, amiloride), potassium supplements or potassium-containing salt substitutes, as well as in patients using other medicines. medicines that increase serum potassium. If it is necessary to use these agents at the same time, it is recommended to check serum potassium more frequently than usual. This drug is clearly less effective in lowering blood pressure in black patients, probably due to the low plasma activity of renin in the black hypertensive population. 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. There are limited data on the efficacy and safety of the medicine in children with hypertension aged> 6 years, but no data on other indications. It is not recommended to use in children for indications other than hypertension.

ACE inhibitors are not recommended during the first trimester of pregnancy and breast-feeding. In the second and third trimester, the use of ACE inhibitors is contraindicated. The use of ACE inhibitors in the second and third trimester of pregnancy is toxic to the fetus (renal dysfunction, oligohydramnios, delayed ossification of the skull) and the newborn (renal failure, hypotension, hyperkalemia). In the case of exposure to the drug from the second trimester of pregnancy, it is recommended to control renal function and skull development in ultrasound. Newborns of mothers who have taken the drug should be carefully monitored for hypotension. Limited pharmacokinetic data indicate very low levels in breast milk. Use during breastfeeding of premature babies and newborns is not recommended for the first few weeks after delivery due to the potential for cardiovascular and renal exposure and insufficient clinical experience. For older infants, the use of the drug by breastfeeding women may be considered if treatment is necessary for the mother and the child is observed because of the possibility of side effects.

Very often: blurred vision, dizziness, cough, nausea, weakness. Common: headaches, depression, hypotension (including orthostatic hypotension), syncope, chest pain, arrhythmia, angina pectoris, tachycardia, shortness of breath, diarrhea, abdominal pain, dysgeusia, rash, hypersensitivity reactions / angioneurotic edema (swelling 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, anxiety, paresthesia, dizziness, orthostatic hypotension, palpitations, myocardial infarction or cerebrovascular incident (probably secondary to significant hypotension in patients high risk), rhinorrhea, hoarseness, hoarseness, bronchospasm / asthma, intestinal obstruction, pancreatitis, vomiting, indigestion, constipation, anorexia, gastric irritation, dry mouth, peptic ulcer, excessive sweating, pruritus, urticaria, alopecia, renal dysfunction, renal failure, proteinuria, impotence, muscle spasms, hot flushes, tinnitus, malaise, fever, increased blood urea, hyponatremia. Rare: neutropenia, decreased hemoglobin, hematocrit reduction, thrombocytopenia, agranulocytosis, bone marrow depression, pancytopenia, lymphadenopathy, autoimmune diseases, nightmares, sleep disorders, Raynaud's syndrome, lung infiltrates, rhinitis, allergic alveolitis / eosinophilic inflammation lungs, oral inflammation / inflammation of the mouth, tongue inflammation, liver failure, hepatitis (hepatocellular or cholestatic), hepatic necrosis, cholestasis (including jaundice), erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic necrosis -difficultaneous epidermis, pemphigus, erythema, oliguria, gynecomastia, increase in liver enzymes, increase in serum bilirubin. Very rare: angioedema of the intestines. Frequency unknown: syndrome of abnormal secretion of antidiuretic hormone. A set of symptoms is also described, which may include some or all of the following symptoms: fever, polyserositis, vasculitis, myalgia and / or myositis, arthralgia and / or arthritis, increased serum antinuclear antibodies, elevated ESR, eosinophilia and leukocytosis, rash, hypersensitivity to light and other skin symptoms.

Orally. Dosages should be determined individually.Hypertension. Adults: the initial dose is 5-20 mg once a day, depending on the severity of hypertension and the patient's desired response to treatment. In mild hypertension, the recommended dose is 5-10 mg. Patients who have an increased activity of the renin-angiotensin-aldosterone system (eg, renovascular hypertension, excessive salt loss and / or decreased circulating blood volume, heart failure or severe hypertension) may experience an aggravated decrease in blood pressure after the initial dose. In these patients, an initial dose of 5 mg or less is recommended, and treatment should be started under medical supervision. In patients taking high doses of diuretics, special care should be taken at the beginning of treatment, because symptomatic hypotension may occur after the first dose. In these patients, it is recommended to administer the drug at an initial dose of 5 mg or less. 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.Children and youth: m.c. 20-50 kg initial dose 2.5 mg once a day; b.w. ≥50 kg initial dose 5 mg once a day; maximum dose - at m.c. 20-50 kg is 20 mg a day, at m.c. ≥50 kg is 40 mg. It is not recommended for neonates and children with glomerular filtration <30 ml / min / 1.73 m²due to the lack of sufficient data.Heart failure / asymptomatic left ventricular dysfunction. In the treatment of symptomatic heart failure, the drug is used in combination with diuretics and, if necessary, with digitalis and β-blocker glycosides. The initial dose in patients with symptomatic heart failure or asymptomatic left ventricular dysfunction 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 of heart failure or if it has been controlled effectively, the dose should be increased gradually to the usual maintenance dose of 20 mg, given as a single dose or as two divided doses, depending on the patient's tolerability. Adaptation of the maintenance dose should take place in the period of 2-4 weeks. The maximum maintenance dose is 40 mg per day administered in two divided doses. Week 1: 1.-3. day: 2.5 mg / day in a single dose; 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, it is necessary to check blood pressure, kidney function and determination of serum potassium. To prevent hypotension, it is recommended to reduce the diuretic dose early, if possible, before starting treatment. The occurrence of hypotension after the initial dose does not mean that it will recur after long-term treatment and does not rule out the continued use of this drug. In patients with renal failure, the intervals between subsequent doses should be prolonged and / or the dose should be reduced; initial dose depends on creatinine clearance: in patients with creatinine clearance 30-80 ml / min is 5-10 mg / day, in patients with creatinine clearance 10-30 ml / min - 2.5 mg / day, in patients with a creatinine clearance creatinine ≤10ml / min the initial dose is 2.5 mg / day on dialysis days. The drug is removed during dialysis. The dose of the drug in the days between dialysis treatments should be adjusted to the arterial blood pressure. In elderly patients, the dose should be adjusted depending on the patient's renal function.