Index of drugs

Treatment of spontaneous and renal arterial hypertension as monotherapy or in combination with other blood pressure lowering drugs. Treatment of heart failure as monotherapy or in combination with diuretics and in certain cases with digitalis preparations. Treatment of haemodynamically stable patients in the early (24 h) phase of myocardial infarction, to prevent the development of left ventricular dysfunction and heart failure. Treatment of patients with hypertensive diabetes mellitus and type 2 diabetes and initial nephropathy.

Table. contains 5 mg, 10 mg or 20 mg lisinopril.

Angiotensin converting enzyme inhibitor. The mechanism of action of lisinopril is the inhibition of angiotensin-converting enzyme. The angiotensin convertase is an enzyme that converts angiotensin I to angiotensin II, which has a strong vasodilator effect and increases blood pressure. Angiotensin II also increases the secretion of aldosterone by the adrenal cortex. Inhibition of angiotensin converting activity results in a decrease in angiotensin II concentration in the blood plasma and a reduction in the secretion of aldosterone, which may cause a small increase in serum potassium. Administration of lisinopril with hypertension resulted in a decrease in blood pressure measured in supine and standing position, without reflex tachycardia. Hemodynamic tests showed that the reduction in blood pressure was caused by a decrease in the blood flow resistance of the peripheral arteries, which was accompanied by slight changes in stroke volume or heart rate. In clinical trials, antihypertensive activity started in the majority of patients after 1-2 hours and the maximum reduction in blood pressure occurred after 6 hours. The drug administered at the recommended doses once a day works for 24 hours. After oral administration, lisinopril is absorbed from the gastrointestinal tract in approximately 25%; food does not affect the absorption of the drug. The maximum concentration in the blood occurs after 6-8 h. Lisinopril does not bind to plasma proteins (except for angiotensin convertase). It is not metabolised and is excreted unchanged by the kidneys.

Hypersensitivity to lisinopril, other ACE inhibitors or to any of the excipients. History of angioneurotic edema associated with previous treatment with ACE inhibitor. Hereditary or idiopathic angioedema. 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).

Do not start treatment with lisinopril in patients with acute myocardial infarction if there is a risk of acute hemodynamic disturbances after using vasodilators - patients with systolic blood pressure 100 mm Hg or with symptoms of cardiogenic shock. In patients with heart failure, concomitant renal insufficiency or without renal failure, with ischemic heart disease or arteries stenosis of the brain supplying brain, severe hepatic insufficiency, high dose diuretic therapy, hyponatraemia or functional renal impairment, the pressure values ​​should be frequently monitored at the beginning of the treatment and after each change of dose of lisinopril and / or diuretic. Carefully use in patients with narrowing of the left ventricular outflow tract. In patients with bilateral renal artery stenosis or stenosis of the artery supplying the blood to one kidney, in whom an increase in serum urea and creatinine has been observed, the dose should be reduced or discontinued to take a diuretic and / or lisinopril. In patients treated with ACE inhibitors with impaired renal function or collagen vascular disease, neutropenia or agranulocytosis has been reported; the image of blood counts should be properly assessed. In the case of angioedema of the face, limbs, lips, tongue, glottis and / or larynx, it is necessary to immediately discontinue lisinopril and administer the treatment in the hospital until the symptoms subside (no less than 12-24 h).If jaundice occurs, the drug should be discontinued and the liver should be monitored until the disorder is resolved. Due to the presence of anaphylactoid reactions in patients treated with ACE inhibitors that are subjected to hemodialysis with high-flow membranes, another type of dialysis membrane should be used, or an ACE inhibitor should be withdrawn early and other treatment should be given. In rare cases, patients receiving ACE inhibitors during apheresis of low-density lipoprotein (LDL) with dextran sulphate have reported life-threatening anaphylactic reactions. These reactions can be avoided by temporarily suspending treatment with an ACE inhibitor before each apheresis. Similarly, in the case of desensitized patients (eg using hymenoptera venom), persistent anaphylactoid reactions occurred. Such reactions were prevented by temporary discontinuation of ACE inhibitors. Patients undergoing general anesthesia or extensive surgery have an increased risk of hypotension. It should be prevented by increasing the volume of circulating blood, and if it occurs, appropriate treatment should be implemented. In diabetic patients treated with oral antidiabetic agents or insulin, glycemic control should be closely monitored during the first month of treatment with an ACE inhibitor. 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 efficacy and safety of lisinopril in children has not been established.

The drug should not be used during the first trimester of pregnancy. The preparation is contraindicated for use in the second and third trimester of pregnancy. The use of ACE inhibitors in the second and third trimester of pregnancy causes toxic effects on the human fetus (decreased renal function, oligohydramnios, delayed ossification of the skull) and the newborn (renal failure, hypotension, hyperkalemia). Women of childbearing potential must use effective contraception during treatment. If during treatment it turns out that the patient is pregnant, the drug should be discontinued and the treatment should be changed. Do not use the drug during breast-feeding. An alternative treatment is preferred with products with a better safety profile when breastfeeding, especially when feeding a newborn or premature baby.

Common: headaches and dizziness; orthostatic symptoms (including hypotonia); cough; diarrhea, vomiting; kidney problems. Uncommon: mood changes, paresthesia, peripheral dizziness, taste disturbances, sleep disorders; myocardial infarction (or a cerebrovascular event probably secondary to excessive hypertension in patients at risk), palpitations, tachycardia, Raynaud's syndrome; cerebrovascular stroke, probably secondary to significant hypotension in high-risk patients; rhinitis; nausea, abdominal pain, indigestion; rash, pruritus; impotence; fatigue, asthenia; elevation of urea in the blood, increase in blood creatinine, increase in liver enzymes, hyperkalemia. Rare: reduction in hemoglobin, hematocrit reduction, and inadequate secretion of antidiuretic hormone; entanglement; dryness of the oral mucosa; hypersensitivity / angioneurotic edema: angioneurotic edema of the face, limbs, lips, tongue, glottis and / or larynx, urticaria, alopecia, psoriasis; uremia, acute renal failure, proteinuria; gynecomastia; hyponatraemia, elevation of bilirubin in the blood plasma. Very rare: bone marrow suppression, anemia, thrombocytopenia, leukopenia, neutropenia, agranulocytosis, haemolytic anemia, lymphadenopathy, autoimmune disease; hypoglycemia; bronchial spasms, rhinosinusitis, allergic alveolitis / eosinophilic pneumonia; pancreatitis, angioedema of the intestines, hepatitis - parenchymal and cholestatic, jaundice, hepatic failure; increased sweating, pemphigus, toxic epidermal necrolysis (Lyell's syndrome), Stevens-Johnson syndrome, erythema multiforme, pseudo-skin lymphoma; oliguria, anuria.Gout has also been reported; lower libido, depression, stroke, blurred vision, anorexia, constipation, flatulence, urinary tract infections, chest pain, redness, syncope. A set of symptoms was reported in which there were single or simultaneously: fever, vasculitis, myalgia, arthritis pain and inflammation, positive anti-nuclear antibodies, increased ESR, eosinophilia, leukocytosis, rash, photodermatitis and other dermatological symptoms.

Orally. The dose should be adjusted individually depending on the patient's response and the value of blood pressure.Hypertension. The recommended starting dose is 10 mg. In patients with renovascular hypertension, water-electrolyte imbalance, diuretic therapy or renal insufficiency, the initial dose should be reduced. The usual maintenance dose is 20-40 mg / day. In some patients, the expected reduction in blood pressure occurs after 2-4 weeks of treatment with maintenance doses. The maximum dose used in long-term, controlled clinical trials was 80 mg / day, but its use did not increase the effectiveness of treatment. In patients concomitantly treated with diuretics, if possible, the diuretic should be discontinued 2-3 days before treatment with lisinopril. In patients who can not take their diuretic, treatment with lisinopril should be started with a dose of 5 mg - blood pressure should be monitored until the expected reduction and additionally for one hour. Subsequent doses of lisinopril should be determined based on the pressure value. In patients with renovascular hypertension, a lower initial dose of 2.5 mg or 5 mg is recommended. Later, the daily dose can be gradually increased by adjusting it to the arterial blood pressure.Heart failure. Lisinopril can be used in combination with diuretics and digitalis preparations. The starting dose is 2.5 mg once a day, in the morning. The maintenance dose is 5-20 mg once a day. In patients with low systolic blood pressure (<100 mmHg), treatment should be started under close medical supervision. The greatest reduction in blood pressure occurs about 6-8 hours after the initial dose. In patients with an increased risk of symptomatic hypotension (patients with hyponatraemia, hypovolaemia or high diuretic therapy), it is necessary to correct the disorder before initiating lisinopril and, if possible, to reduce the diuretic dose. In patients with heart failure and hyponatremia (serum sodium <130 mEq / L) or moderate or severe renal impairment (creatinine clearance <30 ml / min or serum creatinine> 3 mg / dl) low doses should be used initial 2.5 mg / day administered under close medical supervision.Early phase of myocardial infarction. In haemodynamically-efficient patients, treatment with lisinopril should be started within 24 hours of the onset of myocardial infarction. The first, one-time dose is 5 mg. After 24 hours, 5 mg should be given again, followed by a dose of 10 mg after 48 hours. Then continue to take 10 mg once a day for 6 weeks. In combination with lisinopril, you should administer (if there are no contraindications) the usual medications for myocardial infarction: anticoagulant, anti-platelet aggregation, β-adrenergic blocking. Patients with low systolic blood pressure (≤120 mmHg) should take a daily dose of 2.5 mg at the beginning of treatment or for the first 3 days after MI. If hypotension occurs during the first 6 weeks of treatment (systolic blood pressure ≤100 mmHg), reduce the single maintenance dose to 5 mg or 2.5 mg daily. If prolonged and severe hypotension occurs (systolic blood pressure <90 mmHg occurring longer than 1 hour), the drug should be discontinued. Treatment with maintenance doses lasts for 6 weeks. In patients who develop symptoms of heart failure, treatment should continue with the use of lisinopril as in heart failure. Lisinopril can be used in combination with intravenous or transdermal nitroglycerine. The dosage rules for lisinopril have not been established in patients with acute myocardial infarction and coexisting severe renal failure.Diabetic nephropathy. In patients with hypertension and insulin-dependent diabetes mellitus (type 2) and with initial nephropathy, the starting dose is 10 mg per day and may be increased to 20 mg per day to achieve diastolic blood pressure <90 mmHg measured in the sitting position. In the case of renal dysfunction (creatinine clearance <80 ml / min), the initial dose of the drug should be adjusted to the value of creatinine clearance.Dosing in patients with renal insufficiency. The creatinine clearance should be taken into consideration when establishing the dose in patients with impaired renal function: 31-70 ml / min - initial dose 5-10 mg daily; 10-30 ml / min - initial dose 2.5-5 mg per day; <10 ml / min and dialysis patients - initial dose 2.5 mg daily (lisinopril is eliminated from plasma during hemodialysis, patients should be given the appropriate daily dose of lisinopril after hemodialysis). The maximum daily dose in patients with renal insufficiency is 40 mg per day.Children. Hypertension in children and adolescents from 6 to 16 years of age. Children about the month of 20 to 50 kg: the initial dose of 2.5 mg once a day, the dose should be increased up to a maximum dose of 20 mg / day. Children about the month of ≥50 kg: starting dose of 5 mg once a day, the dose should be increased to a maximum dose of 40 mg / day. The dosage> 0.61 mg / kg has not been studied. (or> 40 mg) in children and adolescents. In children with impaired renal function, a lower starting dose or prolonged dose interval should be considered. The use of lisinopril in children with severe renal impairment is not recommended (GFR <30 ml / min / 1.73 m²).
The drug should be taken once a day, at about the same time of the day, regardless of the meal.