Lisinopril-ALSI, tablets 10 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 No pronounced increase in BP was observed when the drug was abruptly withdrawn.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

Active ingredient

Composition

One tablet contains:

the active ingredient:

lisinopril dihydrate – 10.9 mg , which corresponds to 10 mg of lisinopril;

excipients:

lactose monohydrate (milk sugar) – 20.0 mg,

microcrystalline cellulose – 43.8 mg,

pregelatinized starch (starch 1500) – 22.0 mg,

colloidal silica (aerosil) – 0.3 mg,

talcum powder – 2.0 mg,

magnesium stearate – 1.0 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 (there is an increased risk of hyperkalemia, especially in impaired renal function), so they can be prescribed together only on the basis of an individual decision of the treating doctor with regular monitoring of serum potassium levels and renal function.

Cautiously may be used together:

With diuretics: When an additional diuretic is administered to a patient taking lisinopril, there is usually an additive antihypertensive effect – the risk of a pronounced decrease in BP;

– with other antihypertensive agents (additive effect);

– with nonsteroidal anti-inflammatory drugs (indomethacin, etc.), estrogens, as well as adrenostimulants – decrease antihypertensive effect of lisinopril;

– with lithium (lithium excretion may decrease, so serum lithium concentration should be monitored regularly);

– with antacids and colestyramine – decrease 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, after taking the first dose, a physician’s control for several hours is recommended (maximum action 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 (BP control, 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.

Creatinine clearance

Initial dose

ml/min

mg/day

30-70

5-10

10-30

2.5-5

less than 10

2.5

(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 dose 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.

The elderly often have 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 every 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

The most common manifestation of BP decrease is 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 significant, unpredictable decrease in BP during major surgical interventions, as well as during the use of other drugs that cause BP reduction.

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 taken into account that dizziness may occur, so caution should be exercised.

Synopsis

Circular tablets are white or almost white.

The 10 mg tablets are flat-cylindrical with a bevel and a groove.

Features

Intake. 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 is 29%.

Distribution. Almost does not bind with blood 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.

Elimination. 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 the absorption and clearance of lisinopril are decreased.

In patients with renal failure, lisinopril concentrations are several times higher than plasma concentrations in volunteers, with increased time to peak plasma concentrations and increased elimination 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 from the use of ACE inhibitors, hereditary Quincke’s edema, age under 18 years (effectiveness and safety not established).

The tablets contain lactose; therefore, the drug should not be taken by patients with rare hereditary diseases, such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption.

WARNING

With caution, prescribe the drug in: Severe renal dysfunction, bilateral renal artery stenosis or single renal artery stenosis with progressive azotemia, condition after renal transplantation, renal failure, azotemia, hyperkalemia, aortic estuary stenosis, hypertrophic obstructive cardiomyopathy, primary hyperaldosteronism, arterial hypotension, cerebrovascular disease (incl.cerebrovascular diseases (including insufficiency of cerebral circulation), coronary heart disease, coronary insufficiency, autoimmune systemic connective tissue diseases (including scleroderma, systemic lupus erythematosus); inhibition of bone marrow hematopoiesis; on a diet with sodium restriction: hypovolemic conditions (including those caused by diarrhea, vomiting); in old age.

Side effects

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: (0.1%) Angioneurotic edema (face, lips, tongue, larynx or epiglottis, upper and lower extremities).

Cardiovascular system: marked BP decrease, orthostatic hypotension, renal dysfunction, heart rhythm disorders, palpitations.

As to the central nervous system: increased fatigue, somnolence, convulsive twitching of the muscles of the limbs and lips.

Hematopoietic system disorders: leukopenia, neutropenia, agranulocytosis, thrombocytopenia are possible; with prolonged treatment – a slight decrease in hemoglobin concentration and hematocrit, erythrocytopenia.

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

Rarely occurring side effects (less than 1%):

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

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

Skin disorders: urticaria, increased sweating, itching, alopecia.

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

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

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 BP decrease; dry mouth, drowsiness, urinary retention, constipation, restlessness, increased irritability.

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

Lisinopril may be eliminated from the body by hemodialysis.

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