Lisinopril-ALSI, tablets 20 mg 30 pcs

A ACE inhibitor, reduces the formation of angiotensin II from angiotensin I. Reduction of angiotensin II leads to a direct reduction of aldosterone release. Reduces bradykinin degradation and increases prostaglandin synthesis. Reduces total peripheral vascular resistance, blood pressure (BP), preload, pulmonary capillary pressure, causes an increase in minute blood volume and increases myocardial exercise tolerance in patients with chronic heart failure. Dilates arteries to a greater extent than veins. Some effects are explained by the effect on tissue renin-angiotensin systems. Long-term use reduces myocardial hypertrophy and resistive arterial wall hypertrophy. It improves the blood supply to the ischemic myocardium.

The ACE inhibitors prolong life expectancy in patients with chronic heart failure, slow the progression of left ventricular dysfunction in patients who have had myocardial infarction without clinical manifestations of heart failure. The antihypertensive effect begins after approximately 6 hours and lasts for 24 hours. The duration of the effect also depends on the dose. The onset of action is in 1 hour. The maximum effect is determined after 6-7 hours. In case of arterial hypertension, the effect is noted during the first days after the start of treatment, the stable effect develops after 1-2 months. No pronounced increase in BP was observed when the drug was abruptly withdrawn.

In addition to BP reduction, lisinopril decreases albuminuria. In patients with hyperglycemia, it promotes normalization of function of damaged glomerular endothelium.

Lisinopril has no effect on blood glucose concentration in diabetic patients and does not lead to increased incidence of hypoglycemia.

Indications

• Arterial hypertension (in monotherapy or in combination with other antihypertensive agents);
• Cronic heart failure (as part of combined therapy for the treatment of patients taking foxglove drugs and/or diuretics);
• Diabetic nephropathy (reduction of albuminuria in insulin dependent patients with normal BP and insulin independent patients with hypertension).

.

Active ingredient

Lisinopril

Composition

One tablet contains:

Active ingredient:

Lisinopril dihydrate – 21.8 mg, which corresponds to 20 mg of lisinopril.

Auxiliary substances:

Lactose monohydrate (milk sugar) – 40.1 mg;

Microcrystalline cellulose – 87.6 mg;

Pregelatinized starch (starch 1500) – 44.0 mg;

Colloidal silica (aerosil) – 0.5 mg;

Talc – 4.0 mg;

Magnesium stearate – 2.0 mg.

Interaction

Lisinopril decreases potassium excretion when treated with diuretics.

Particular caution is required when using the drug concomitantly with: potassium-saving diuretics (spironolactone, triamterene, amiloride), potassium, table salt substitutes containing potassium (increased risk of hyperkalemia, especially with impaired renal function), so they can be prescribed together only on the basis of an individual decision of the treating physician with regular monitoring of serum potassium levels and renal function.

Cautiously may be used together:

• with diuretics: When an additional diuretic is given to a patient taking lisinopril, there is usually an additive antihypertensive effect – risk of marked BP reduction;

• with other antihypertensive agents (additive effect);

• with nonsteroidal anti-inflammatory drugs (indomethacin, etc.), estrogens, and adrenostimulants – decreased antihypertensive effect of lisinopril;

• With lithium (lithium excretion may decrease, so serum lithium concentration should be monitored regularly);

• with antacids and colestyramine – reduce absorption in the gastrointestinal tract.

Alcohol increases the effect of the drug.

Directions for use

Ingestion, regardless of meals. In patients with arterial hypertension who are not receiving other hypotensive agents, 5 mg once daily is prescribed. If there is no effect, the dose is increased every 2-3 days by 5 mg to an average therapeutic dose of 20-40 mg/day (an increase in dose over 40 mg/day usually does not lead to further BP reduction). The usual daily maintenance dose is 20 mg. The maximum daily dose is 40 mg.

The full effect usually develops in 2-4 weeks from the beginning of treatment, which should be taken into account when increasing the dose. If the clinical effect is insufficient, it is possible to combine the drug with other hypotensive agents.

If the patient has received prior treatment with diuretics, the use of these drugs should be stopped 2 to 3 days before starting lisinopril. If this is not feasible, the initial dose of lisinopril should not exceed 5 mg per day. In this case, it is recommended that after the first dose, a physician follow up for several hours (the maximum effect is reached after about 6 hours), since a marked decrease in BP may occur.

In renovascular hypertension or other conditions with increased activity of renin-angiotensin-aldosterone system it is reasonable to prescribe also low initial dose – 2.5-5 mg per day, under increased medical control (control of BP, renal function, serum potassium concentration). The maintenance dose, while continuing close monitoring by a physician, should be determined depending on the dynamics of BP.

In renal failure due to the fact that lisinopril is excreted through the kidneys, the initial dose should be determined according to creatinine clearance, then according to the response, a maintenance dose should be established with frequent monitoring of renal function, serum potassium, sodium levels.

(including patients treated with hemodialysis)

In persistent arterial hypertension, long-term maintenance therapy of 10-15 mg/day is indicated.

In chronic heart failure, start with 2.5 mg once daily, with subsequent increases of 2.5 mg after 3-5 days to the usual, maintenance daily dose of 5-20 mg. The dose should not exceed 20 mg daily.

In the elderly there is often a more pronounced long-term hypotensive effect due to the decreased excretion rate of lisinopril (it is recommended to start treatment with 2.5 mg/day).

Acute myocardial infarction (as part of combination therapy)

In the first day, 5 mg orally, then 5 mg every other day, 10 mg after two days and then 10 mg once daily. In patients with acute myocardial infarction, use the drug for at least 6 weeks.

At the beginning of treatment or during the first 3 days after acute myocardial infarction in patients with low systolic BP (120 mm Hg or lower) a lower dose of 2.5 mg should be prescribed. In case of BP decrease (systolic BP below or equal to 100 mmHg), the daily dose of 5 mg may be temporarily reduced to 2.5 mg, if necessary. In case of prolonged marked BP lowering (systolic BP below 90 mmHg for more than 1 hour), treatment with lisinopril should be stopped.

Diabetic nephropathy

In patients with insulin-independent diabetes mellitus, 10 mg of lisinopril once daily is used. The dose can be increased to 20 mg once daily, if necessary, in order to achieve a diastolic BP below 75 mmHg in sitting position. The dosage is identical in patients with insulin-dependent diabetes mellitus in order to achieve values of diastolic BP below 90 mmHg in sitting position.

Special Instructions

Symptomatic hypotension

Most often a pronounced decrease in BP occurs with a decrease in fluid volume caused by diuretic therapy, reduction of salt in food, dialysis, diarrhea or vomiting. In patients with chronic heart failure with or without concomitant renal failure, pronounced BP reduction is possible. It is more often found in patients with severe stage of chronic heart failure, as a consequence of high doses of diuretics, hyponatremia or impaired renal function. In such patients lisinopril treatment should be started under close medical supervision (choose the dose of drug and diuretics with caution).

The same rules should be followed when prescribing for patients with coronary heart disease, cerebrovascular insufficiency, in whom a sharp decrease in BP may lead to myocardial infarction or stroke.

Transient hypotensive reaction is not a contraindication for the next dose of the drug.

Lisinopril may decrease BP in some patients with chronic heart failure but with normal or lower BP, which is usually not a reason to discontinue treatment.

Before starting lisinopril treatment, if possible, normalize sodium concentration and/or replenish lost fluid volume, carefully monitor the effect of the initial dose of lisinopril on the patient.

In cases of renal artery stenosis (especially bilateral stenosis, or in the presence of artery stenosis of the single kidney), and circulatory failure due to lack of sodium and/or fluid, lisinopril use may lead to impaired renal function, acute renal failure, which is usually irreversible after drug withdrawal.

In acute myocardial infarction

The use of standard therapy (thrombolytics, acetylsalicylic acid, beta-adrenoblockers) is indicated. Lisinopril may be combined with intravenous or therapeutic nitroglycerin transdermal systems.

Surgery/general anesthesia

Lisinopril, by blocking angiotensin II formation, may cause a marked, unpredictable decrease in BP during major surgical interventions and also with other drugs that lower BP.

In elderly patients, the same dose leads to higher blood concentrations of the drug, so extra caution is required in determining the dose.

Because the potential risk of agranulocytosis cannot be excluded, periodic monitoring of blood counts is necessary. Anaphylactic shock may occur when the drug is used in dialysis with a polyacrylonitrile membrane, so either a different type of dialysis membrane or administration of other antihypertensive agents is recommended.

Influence on driving and operating ability

There are no data on the effect of lisinopril on driving and operating ability when used in therapeutic doses, but it should be considered that dizziness may occur, so caution should be exercised.

Synopsis

Circular tablets are white or almost white.

The 20 mg tablets are flat-cylindrical with a bevel and a groove.

Features

absorption After oral administration about 25% of lisinopril is absorbed from the gastrointestinal tract. Food intake does not affect absorption of the drug. Absorption is on average 30%, bioavailability 29%.

Distribution. It is almost not bound to plasma proteins. Maximal concentration in blood plasma (90 ng/ml) is reached after 7 hours. Hematoencephalic and placental barrier permeability is low.

Metabolism.Lisinopril is not biotransformed in the body.

Evolution. It is excreted unchanged by the kidneys. The elimination half-life is 12 hours.

Pharmacokinetics in selected patient groups

In patients with chronic heart failure absorption and clearance of lisinopril are reduced.

In patients with renal insufficiency the concentration of lisinopril is several times higher than plasma concentrations in volunteers, with increased time to reach maximum plasma concentration and increased half-life.

In elderly patients, plasma concentrations and area under the curve are 2-fold greater than in younger patients.

Contraindications

• Hypersensitivity to lisinopril or other ACE inhibitors;

• History of angioedema, including history of ACE inhibitors;

• Hereditary Quincke’s edema;

• Age <18 years (effectiveness and safety not established).

The tablets contain lactose; therefore, the drug should not be taken by patients with rare hereditary conditions such as:

• Galactose intolerance;

• Lactase deficiency or glucose-galactose malabsorption.

The drug is prescribed with caution in:

• Developed renal dysfunction;

• Bilateral renal artery stenosis or single renal artery stenosis with progressive azotemia;

• Post renal transplantation;

• Renal failure;

• Azotemia;

• Hyperkalemia;

• Aortic orifice stenosis;

• Hypertrophic obstructive cardiomyopathy;

• Primary hyperaldosteronism;

• Arterial hypotension;

• Cerebrovascular disease (includingч. cerebrovascular disease;

• Ischemic heart disease;

• Coronary artery disease;

• Autoimmune systemic connective tissue disease (includingч. Scleroderma, systemic lupus erythematosus); Inhibition of medullary hematopoiesis;

• On a sodium restricted diet: hypovolemic conditions (includingIncluding as a result of diarrhea, vomiting;

• In the elderly.

.

Side effects

The most common side effects:dizziness, headache (in 5-6% of patients), weakness, diarrhea, dry cough (3%), nausea, vomiting, orthostatic hypotension, skin rash, chest pain (1-3%).

Other side effects (incidence < 1%):

immune system side effects: (0.1%) angioedema (face, lips, tongue, larynx or epiglottis, upper and lower extremities).

Cardiovascular system:A marked decrease in BP, orthostatic hypotension, impaired renal function, heart rhythm disorders, palpitations.

From the central nervous system: increased fatigue, drowsiness, convulsive twitching of the muscles of the limbs and lips.

Hematopoietic system disorders: Leukopenia, neutropenia, agranulocytosis, thrombocytopenia may occur, with long-term treatment – a slight decrease in hemoglobin concentration and hematocrit, erythrocytopenia.

Laboratory findings: hyperkalemia, azotemia, hyperuricemia, hyperbilirubinemia, increased activity of “liver” enzymes, especially in the presence of a history of renal disease, diabetes and renovascular hypertension.

Rare side effects (less than 1%):

Cardiovascular side effects:painful palpitations; tachycardia; myocardial infarction; cerebrovascular stroke in patients at increased risk of disease, due to markedly lower BP.

Gastrointestinal tract:Dry mouth, anorexia, dyspepsia, changes in taste, abdominal pain, pancreatitis, hepatocellular or cholestatic jaundice, hepatitis.

Skin side: urticaria, increased sweating, skin itching, alopecia.

Retinary system disorders:renal dysfunction, oliguria, anuria, acute renal failure, uremia, proteinuria.

From the immune system: syndrome, including accelerated erythrocyte sedimentation rate (ESR), arthralgia, and the appearance of antinuclear antibodies.

From the central nervous system: asthenic syndrome, mood lability, confusion, decreased potency.

Others:myalgia, fever, impaired fetal development.

Overdose

Symptoms (occurs with a single dose of 50 mg or more): marked decrease in BP; dry mouth, drowsiness, delayed urination, constipation, restlessness, increased irritability.

treatment:symptomatic therapy, intravenous fluid administration, control of BP, water-electrolyte balance and normalization of the latter.

Lisinopril can be eliminated from the body by hemodialysis.

Similarities

Diroton, Lisinopril, Lisinopril Stada, Lisinopril-Teva, Lisinopril-ALSI