Lizinopril-Astropharm 5 mg tablets # 20

Lisinopril instructions for use

Composition:

active ingredient: lisinopril; 1 tablet contains lisinopril dihydrate in terms of 5 mg, or 10 mg or 20 mg;
auxiliary substances: calcium hydrophosphate, mannitol (E 421), corn starch, magnesium stearate, silicon dioxide colloidal anhydrous.

Dosage form

Tablets: 5 mg № 20, 10 mg № 20, 10 mg № 30, 20 mg № 20.

Pharmacotherapeutic group

Angiotensin converting enzyme (ACE) inhibitors. The code of automatic telephone exchange С09А А03.

Clinical characteristics

Indications

Arterial hypertension.

Chronic heart failure.

Acute myocardial infarction in patients with stable hemodynamic parameters (systolic blood pressure> 100 mm Hg).

Diabetic nephropathy in diabetes mellitus (in patients with insulin-dependent diabetes mellitus type II).

Contraindications

Hypersensitivity to lisinopril, to other components of the drug or to other ACE inhibitors.

Angioedema in the anamnesis (including after the use of ACE inhibitors, idiopathic and hereditary edema).

Aortic or mitral stenosis or hypertrophic cardiomyopathy with severe hemodynamic disturbances.

Bilateral stenosis of the renal artery or stenosis of the artery of a single kidney; acute myocardial infarction with unstable hemodynamics; cardiogenic shock; simultaneous application of the preparation and high-permeability membranes with polyacrylonitrile sodium-2-methylalenesulfonate (for example, AN 96) in case of urgent dialysis; patients with a serum creatinine level ≥ 220 μmol / l.

Pregnant women or women who plan to become pregnant (see section "Use during pregnancy or lactation").

Dosing and Administration

Tablets Lizinopril-Astropharmum are taken orally 1 time per day, preferably at the same time, regardless of food. The daily dose is selected individually depending on the patient's response and blood pressure.

Arterial hypertension.

The drug is used as a monotherapy or in combination with other classes of antihypertensive drugs.

The initial dose.

With arterial hypertension, the recommended initial dose is 10 mg per day. In patients with increased activity of the renin-angiotensin-aldosterone system (in particular, with renovascular hypertension, excessive elimination of sodium chloride from the body and / or dehydration, cardiac decompensation, or severe arterial hypertension), there may be an excessive decrease in blood pressure after the initial dose. In these patients, the recommended initial dose is 2.5-5 mg and the beginning of treatment should be under the supervision of a physician. To obtain a dose of 2.5 mg, use the drug with an appropriate content of the active substance.

For patients with renal failure, the dose should be reduced (see Table 1).

Supportive dose.

The usual effective maintenance dose is 20 mg per day. If the drug at the indicated dose does not provide the proper therapeutic effect within 2-4 weeks, the dose can be further increased. The maximum daily dose is 80 mg per day.

Patients taking diuretics.

In patients previously receiving diuretic therapy, after receiving the first dose of lisinopril-Astropharm, symptomatic arterial hypotension may occur. Treatment with diuretics should be stopped 2-3 days before the start of treatment with Lizinopril-Astropharm. If it is impossible to stop treatment with diuretics, lisinopril is prescribed in an initial dose of 5 mg.It is necessary to monitor the kidney function and the level of potassium in the blood serum. The further dose should be selected depending on blood pressure. If necessary, treatment with diuretics can be resumed.

Patients with renal insufficiency.

In patients with renal insufficiency, the doses are determined depending on the value of creatinine clearance, as shown in Table 1:

Creatinine clearance (ml / min)	Initial dose (mg / day)
<10 (including patients on hemodialysis)	2.5 *
10-30	2.5-5
31-80	5-10

* The dose and / or dosage regimen is set depending on the blood pressure values. The dose can be increased to no more than 40 mg per day with a control of blood pressure.

Chronic heart failure.

Patients with symptomatic heart failure Lisinopril-Astropharm can be used as an adjunct to therapy with diuretics, digitalis drugs or b-blockers. Lizinopril-Astropharm is prescribed in an initial dose of 2.5 mg per day under the supervision of a physician, in order to determine the primary effect on blood pressure. The dose of the drug should be increased by no more than 10 mg, with a time interval of at least 2 weeks and up to a maximum dose of 35 mg per day.

Dose determination should be based on the clinical observation of each patient.

In patients with a high risk of symptomatic arterial hypotension (with excessive excretion of sodium chloride from the body) with or without hyponatremia, with hypovolemia, as well as in patients who received high doses of diuretics, the above-mentioned conditions before treatment should be compensated.

Acute myocardial infarction.

Patients should simultaneously take conventional standard therapy with thrombolytic drugs, acetylsalicylic acid and β-blockers. Lizinopril is compatible with nitroglycerin, administered intravenously or transdermally.

The initial dose (in the first 3 days after the infarction).

Therapy with lisinopril should be started in the first 24 hours after the onset of symptoms of the disease. Therapy should not be started if the systolic blood pressure is below 100 mmHg. The first dose of lisinopril-Astropharm is 5 mg, 24 hours later, a dose of 5 mg is prescribed, then a dose of 10 mg is administered once a day, and then the maintenance dose is 10 mg once a day.

Patients with systolic blood pressure (120 mm Hg or lower) in the first 3 days after myocardial infarction are prescribed a reduced dose of lisinopril - 2.5 mg.

In renal failure (creatinine clearance <80 ml / min), the initial dose of lisinopril-Astropharm should be adjusted depending on the creatinine clearance of the patient (see Table 1).

Supportive dose.

The maintenance dose is 10 mg per day. If arterial hypotension occurs (systolic blood pressure is less than or equal to 100 mm Hg), the maintenance dose of 5 mg is temporarily reduced to 2.5 mg. If prolonged arterial hypotension occurs (systolic blood pressure is less than 90 mm Hg for more than 1 hour), treatment should be stopped.

Treatment should last for 6 weeks, then you need to reassess the patient's condition. In patients who have symptoms of heart failure, continue treatment with lisinopril.

Diabetic nephropathy.

In the treatment of arterial hypertension in patients with type II diabetes and initial nephropathy, the dose of lisinopril-Astropharm is 10 mg per day. If necessary, the dose may be increased to 20 mg per day in order to achieve diastolic blood pressure values below 90 mmHg. in the sitting position.

In renal failure (creatinine clearance <80 ml / min), the initial dose of the drug must be adjusted depending on the creatinine clearance of the patient (see Table 1).

Patients of advanced age.

In clinical studies, there were no differences in efficacy or safety of the drug due to age. The initial dose of lisinopril given to elderly people with reduced renal function should be adjusted according to Table 1. Subsequently, the dosage is determined depending on the response and blood pressure.

Adverse Reactions

Adverse reactions are given at the following frequency: very common (> 1/10), common (≥ 1/100, <1/10), unadulterated (≥ 1/1000, <1/100), rarely common (≥ 1/10 000 , <1/1000), very rarely common (<1/10 000), is unknown (can not be estimated based on available data).

From the hematopoietic and lymphatic systems: rarely common - a decrease in the level of hemoglobin and hematocrit;very rarely common - oppression of bone marrow, anemia, thrombocytopenia, leukopenia, neutropenia, agranulocytosis, hemolytic anemia, lymphadenopathy, autoimmune disease.

From the side of metabolism: very rarely common - hypoglycemia.

From the central nervous system: common - dizziness, headache; Unspread - a change in mood, paresthesia, a violation of taste, sleep disturbance, imbalance, disorientation; rarely common - confusion, violation of scent; unknown - symptoms of depression, faint.

From the cardiovascular system: common - orthostatic effect (including arterial hypotension); non-common - myocardial infarction or cerebrovascular insult, possibly secondary due to excessive arterial hypotension in high-risk patients, palpitation, tachycardia, Raynaud phenomenon.

From the musculoskeletal system: Muscular spasms were registered.

From the respiratory system: common - cough, bronchitis; unexplained - rhinitis, shortness of breath; rarely common - dyspnea, angioedema; very rarely common - bronchospasm, glossitis, sinusitis, allergic alveolitis / eosinophilic pneumonia. Upper respiratory tract infections have been reported.

From the side of the digestive tract: common - diarrhea, vomiting; uncommon - nausea, abdominal pain and indigestion;rarely common - dry mouth, decreased appetite, change in taste; very rarely common - pancreatitis, intestinal angioedema, constipation, hepatitis (hepatocellular or cholestatic), jaundice and liver failure.

Skin: Unresolved - rash, escapes, hypersensitivity / angioedema, swelling of the face, extremities, lips, tongue, glottis and / or pharynx, fever, skin hyperemia; rarely common - hives, alopecia, psoriasis; very rarely common - increased sweating, pemphigus, toxic epidermal necrolysis, Stevens-Johnson syndrome, polymorphic erythema, lymphocytoma of the skin.

A syndrome has been reported that includes one or more symptoms: fever, vasculitis, myalgia, arthralgia / arthritis, the appearance of positive antinuclear antibodies (ANA), acceleration of erythrocyte sedimentation rate (ESR), eosinophilia and leukocytosis, rashes, photosensitivity or other skin manifestations.

From the kidney and urinary system: common - renal dysfunction; rarely common - uremia, acute renal failure; very rarely common - oliguria / anuria.

From the endocrine system: unknown - inadequate secretion of antidiuretic hormone.

From the part of the reproductive system and the mammary glands: uncontrolled - impotence; rarely common - gynecomastia.

The organism as a whole: non-common - increased fatigue, weakness.

Laboratory indices: non-common - increased urea levels in the blood, serum creatinine, hepatic enzymes, hyperkalemia;rarely common - increased serum bilirubin, hyponatremia, proteinuria.

Overdose

Symptoms: arterial hypotension, circulatory shock, electrolyte disorders, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, restlessness and cough.

Treatment: intravenous injection of saline solutions. With arterial hypotension, you should put the patient on his back with his legs raised up. If possible, an infusion of angiotensin II is prescribed and / or intravenously administered catecholamines. If the drug is taken recently, it shows gastric lavage, the use of absorbents and sodium sulfate.Lizinopril is removed from the blood during hemodialysis. For the treatment of persistent bradycardia, the use of a pacemaker is indicated.

It is recommended to constantly monitor laboratory indicators (determination of the level of electrolytes and serum creatinine) and vital functions.

Use during pregnancy or lactation

The drug is contraindicated during pregnancy or lactation.

The drug should not be used by pregnant women or women who plan to become pregnant. If pregnancy is confirmed during treatment with this drug, its use should be stopped immediately and, if necessary, replaced with a drug approved for use by pregnant women.

Children

The safety and efficacy of lisinopril to children have not been established, therefore, Lizinopril-Astropharm should not be prescribed for this age group of patients.

Application features

Symptomatic arterial hypotension.

It is rare in patients with uncomplicated arterial hypertension. In hypertensive patients taking lisinopril, the likelihood of developing arterial hypotension increases with decreasing circulating blood volume (for example, as a result of diuretic treatment, restricting salt intake from food, dialysis, diarrhea or vomiting), and severe forms of renin-dependent hypertension.

Symptomatic arterial hypotension was observed in patients with heart failure, regardless of whether it is combined with renal insufficiency. This is most often observed in patients with severe heart failure who are forced to take large doses of loop diuretics, and who have hyponatremia or functional renal failure. Patients with an increased risk of hypotension need to be closely monitored during the initial treatment period and when choosing a dose.

This also applies to patients with coronary artery disease or cerebrovascular disease, in whom a significant drop in blood pressure can lead to myocardial infarction or impaired cerebral circulation.

In the case of development of arterial hypotension, the patient should be placed on his back and, if necessary, an intravenous solution of sodium chloride. Transient hypotensive reaction is not a contraindication for the subsequent administration of the drug. After the restoration of the effective volume of blood and the disappearance of the transient hypotensive reaction, you can continue treatment with lisinopril.

In some patients with chronic heart failure, with normal or low blood pressure, there may be an additional reduction in systemic arterial pressure when prescribing lisinopril. This effect is expected and is usually not a reason for discontinuing therapy. If symptomatic hypotension occurs, it may be necessary to reduce the dose or stop taking lisinopril.

Arterial hypotension with acute myocardial infarction.

In acute myocardial infarction, lisinopril therapy should not be started if, because of previous treatment with vasodilator drugs, there is a risk of further serious deterioration of hemodynamic parameters. This applies to patients with systolic blood pressure ≤ 100 mm Hg. Art. or with cardiogenic shock. In the first 3 days after myocardial infarction, the dose of the drug should be reduced if the systolic blood pressure ≤ 120 mm Hg. At systolic blood pressure ≤ 100 mm Hg. Art.the maintenance dose should be reduced to 5 mg or temporarily to 2.5 mg. With persistent hypotension (systolic blood pressure ≤ 90 mm Hg for more than 1 hour), therapy with lisinopril should be discontinued.

Aortic and mitral stenosis / hypertrophic cardiomyopathy.

Like other ACE inhibitors, lisinopril should be administered with caution to patients with mitral stenosis or difficulty in ejection from the left ventricle (eg, in aortic stenosis or hypertrophic cardiomyopathy).

Impaired renal function.

In renal failure (creatinine clearance <80 ml / min), the initial dose of lisinopril should be determined depending on the creatinine clearance of the patient (see Table 1), and then depending on the patient's response to treatment. Routine monitoring of potassium and creatinine is part of normal medical practice in these patients.

In patients with heart failure at the beginning of treatment with ACE inhibitors, impaired renal function may be observed.In such situations, described cases of acute renal failure, usually reversible. In some patients with narrowing of both renal arteries or with stenosis of the artery of a single kidney, ACE inhibitors increase the level of urea in the blood and creatinine in the serum; usually these changes occur after discontinuation of medication. The likelihood of this is especially high in renal failure.

In the presence of renovascular hypertension is high risk of severe hypotension and renal insufficiency. In these patients, treatment should start under close medical supervision with low doses, which must be precisely matched. Because diuretics can contribute to the above-described clinical dynamics, during the first weeks of treatment with lisinopril their intake should be discontinued and renal function requires careful monitoring.

Some hypertensive patients without apparent renal vascular disease receiving lisinopril, especially against the background of a diuretic, causing an increase in blood urea and serum creatinine; These changes tend to be minor and transient. The probability of their occurrence is higher in patients with impaired renal function. In such cases it may be necessary to decrease the dose and discontinuation of diuretics and lisinopril.

Treatment of acute myocardial infarction lisinopril not indicated for patients with signs of renal dysfunction in which there is increased levels of serum creatinine 177 umol / L and / or proteinuria 500 mg / day. With the development of renal dysfunction during therapy with lisinopril (serum creatinine concentration of greater than 265 pmol / L or double elevated serum creatinine level in comparison with its level determined prior to treatment) is necessary to stop taking the drug.

Hypersensitivity / angioedema.

Angioedema face, extremities, lips, tongue, vocal cords and larynx rarely develop in patients receiving ACE inhibitors, including Lisinopril. During treatment, angioedema can develop at any time. In this case, receiving lisinopril should be stopped immediately, hold the appropriate treatment and to establish observation of the patient; before releasing the patient, you need to make sure that all symptoms of edema eliminated.

Even in cases where only limited swelling tongue and breathing disorders feature absent, patients may require prolonged observation since treatment with antihistamines and glucocorticosteroids (GCS) may be insufficient.

In some cases fatal registered patients due angioneurotic edema of the larynx or tongue. If the swelling extends to the language, voice communication or larynx may overlap the respiratory tract, particularly in patients who previously underwent surgery on the organs of respiration. In such cases it is necessary to take measures of emergency treatment (administration of adrenaline and / or maintain the airway).

The patient should be under close medical supervision until complete and persistent disappearance of symptoms.

In patients with a history of angioedema unrelated to ACE inhibitors, the risk of angioedema in response to receiving an ACE inhibitor can be increased.

Hemodialysis.

When administering the drug in a dialysis membrane poliakrilvinilovoy may develop anaphylactic reactions. It is recommended to use another type of membranes for dialysis or the use of other groups of medicaments for the treatment of patients with hypertension.

Anaphylactoid reactions at LDL apheresis.

Since for LDL apheresis with dextran sulfate ACE inhibitors may lead to anaphylactic reactions that can be life-threatening, it is necessary to temporarily cancel ACE inhibitors before each apheresis.

Desensitization.

Patients taking ACE inhibitors, amid desensitizing therapy (eg, anti-poison Hymenoptera), developing long-term anaphylactoid reactions. If such patients have refrained from taking ACE inhibitors during desensitization reactions were observed, but the introduction of random ACE provoked anaphylactoid reaction.

Liver failure.

With ACE inhibitors bind development rare syndrome that starts with cholestatic jaundice or hepatitis and proceeds to fulminant hepatic necrosis, sometimes with fatal consequences. The mechanism of this syndrome is not understood. If patients taking lisinopril, jaundice or significantly increases the activity of hepatic enzymes, the drug should be abolished, leaving the patient under medical supervision until symptoms disappear.

Hyperkalemia.

Some patients receiving ACE inhibitors, including lisinopril, there is increasing the level of potassium in the blood serum. The group of hyperkalemia risk include patients with renal insufficiency or diabetes receiving potassium-sparing diuretics or kalisodergaszczye salt substitutes, as well as those patients who are taking other medications that increase the serum potassium level (e.g., heparin).

If reception of the above preparations during the treatment with the ACE inhibitor is considered necessary, it is recommended regular monitoring of the level of potassium in serum.

Patients with diabetes mellitus.

Patients with diabetes who take hypoglycemic agent or insulin, necessary to carefully monitor blood glucose levels during the first month of treatment with an ACE inhibitor.

Lithium.

Usually it is not recommended to combine intake of lithium and lisinopril.

Neutropenia / agranulocytosis.

Patients taking ACE inhibitors can develop neutropenia / agranulocytosis, thrombocytopenia and anemia. In normal renal function and in the absence of complications developing neutropenia rare. Neutropenia and agranulocytosis are reversible and disappear after discontinuation of the ACE inhibitor.

It should exercise extreme caution when assigning lisinopril patients with connective tissue diseases with vascular manifestations undergoing treatment with antidepressants taking allopurinol or procainamide, and the combination of these factors, especially against renal dysfunction.

Some of these patients developed serious infections, which do not always lend themselves to intensive antibiotic therapy. If in the treatment of these patients, lisinopril is used, it is recommended to periodically check the number of white blood cells, and patients should be warned of the need to report any sign of infection.

Race.

ACE inhibitors are more likely to cause the development of angioedema in patients blacks compared with patients of other race. Like other ACE inhibitors, lisinopril may be less effective in lowering blood pressure in black patients compared with other races persons, perhaps due to the higher frequency individuals with low renin population black patients with hypertension.

Cough.

With the use of ACE inhibitors may appear long unproductive cough, which disappear after cessation of treatment. Such cough caused by ACE inhibitors, must be considered in the differential diagnosis of cough.

Surgical interventions / anesthesia.

In patients undergoing surgery or general anesthesia drugs to lower blood pressure, lisinopril may block angiotensin II formation increase under the influence of compensatory renin release. If it is assumed that developing hypotension by this mechanism, it can be corrected increases BCC.

Ability to influence the reaction rate when driving or operating other machines.

When driving or operating other mechanisms need to take into account the possibility of dizziness and fatigue.

The interaction with other drugs and other types of interactions

Diuretics.

When applied simultaneously with diuretic summation marked antihypertensive effect. In patients who are already taking diuretics, especially those who are newly assigned to diuretics, addition of lisinopril can sometimes cause excessive blood pressure reduction. The likelihood of symptoms of hypotension under the influence of lisinopril reduced when to stop taking the diuretic before starting treatment with lisinopril.

Kaliysberigayuschie diuretics kalisodergaszczye supplements or solezameniteli.

Although the level of potassium in the blood serum in clinical trials of ACE inhibitors usually remained within normal limits, in some patients, yet still developing hyperkalemia. The risk associated with hyperkalemia factors, which include renal failure, diabetes and the simultaneous reception of potassium-sparing diuretics (e.g., spironolactone, triamterene or amiloride), as well as potassium-containing food additives or solezameniteley.

Use of the potassium-containing food additives, potassium-sparing diuretics or solezameniteley can lead to a significant increase in potassium level in serum, especially in patients with impaired renal function. During the reception of lisinopril on background kaliyvyvodyaschih diuretics hypokalemia due to their reception may be impaired.

Lithium.

When simultaneous administration of ACE inhibitors lithium and reversibly increases in serum lithium level and toxic effects develop. The use of thiazide diuretics may increase the risk of lithium intoxication and enhance it if it has already caused by the simultaneous reception of ACE inhibitors. Apply simultaneously lisinopril with lithium is not recommended, but in those cases where such a combination is necessary, it is necessary to carry out careful monitoring of lithium levels in blood serum.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin at a dose of ≥ 3 g per day.

Long-term use of NSAIDs can weaken the hypotensive effect of ACE inhibitors. The effects of NSAIDs and ACE inhibitors, to enhance the level of potassium in the serum added, which can cause renal dysfunction. These effects are usually reversible. In some cases, there may be acute renal failure, especially with impaired renal function, such as the elderly or in patients with dehydration.

Gold.

Nitritoidnye reactions (vasodilatation symptoms, including hot flashes, nausea, dizziness, hypotension, which can be very severe) after injection of gold (e.g., sodium aurothiomalate) were observed more frequently in patients treated with ACE inhibitor.

Other antihypertensive agents.

With simultaneous use of lisinopril with other antihypertensive drugs increased hypotensive effect observed. Simultaneous administration of nitroglycerin and other organic nitrates or vasodilators may enhance the hypotensive effect of lisinopril.

Tricyclic antidepressants, anesthetics, and antipsychotics.

Taking certain anesthetics, tricyclic antidepressants and antipsychotics amid ACE inhibitors can enhance hypotension.

Sympathomimetics.

May reduce the hypotensive effect of ACE inhibitors.

Hypoglycemic agents.

Epidemiological studies have shown that simultaneous reception of ACE inhibitors and hypoglycemic agents (insulin and hypoglycemic agents for oral) may potentiate the latter, until the development of hypoglycemia. The probability of such events is particularly high during the first weeks of simultaneous treatment of patients, as well as with impaired renal function.

Acetylsalicylic acid, thrombolytics, b-blockers and nitrates.

Lisinopril can be administered simultaneously with acetylsalicylic acid (at doses that are used in cardiology), thrombolytic agents, β-blockers, and nitrates.

Pharmacological properties

Pharmacodynamics

Lisinopril - an inhibitor of ACE. ACE is peptidildipeptidazoy which catalyzes the conversion of angiotensin I into the vasoconstrictor peptide, angiotensin II, which also stimulates aldosterone secretion. Inhibition of ACE reduces the concentration of angiotensin II in the blood plasma, which reduces the vasopressor activity and aldosterone secretion. The latter reduction can lead to increased concentration of potassium in blood serum.

Because the mechanism of action for hypertension is carried out by inhibition of the renin-angiotensin-aldosterone system, lisinopril has a hypotensive effect in hypertensive patients, even with low-renin. ACE is identical to kininaze-degrading enzymes bradykinin. The role of elevated levels of bradykinin (having pronounced vasodilating properties) during treatment lisinopril fully elucidated and requires further study.

Pharmacokinetics.

Absorption.

After oral administration of lisinopril slowly and not completely absorbed in the digestive tract. Absorption of the drug after ingestion of approximately 25% of the interindividual variability (6-60%). Simultaneous food intake does not affect absorption. The maximum plasma concentration is reached after about 6-8 hours.

Distribution.

Equilibrium in the serum concentrations are attained within 2-3 days after the injection. In addition to the ACE does not bind to plasma proteins.

Metabolism and excretion.

It is not metabolized, excreted in the urine in unchanged form.

It is removed by hemodialysis.

Pharmacokinetics in special patient groups.

If any of kidney excretion lisinopril decreases proportionally to the degree of functional disorders disorders (this decrease becomes clinically important for glomerular filtration below 30 ml / min).

In heart failure, renal clearance is reduced lisinopril.

For elderly patients have higher concentration of lisinopril in the blood plasma and the values of area under the curve "concentration-time" (increased by approximately 60%) than in younger patients.

pharmaceutical characteristics:

Basic physical and chemical properties: white tablets of flat-cylindrical shape with bevelled edges and risk.

Shelf life

3 years.

Storage conditions

Store in a dry, dark place at a temperature of no higher than 25 ° С. Keep out of the reach of children.

Packaging

10 tablets in a blister; 1 or 2 or 3 blisters per box.

Category of leave

On prescription.