Lizinopril-SZ - instructions for use, doses, side effects, contraindications

Composition:Active substance: lisinopril dihydrate in terms of the active substance lisinopril - 5 mg, 10 mg, 20 mg
Excipients: lactose monohydrate (sugar milk) - 74.25 mg, 148.5 mg, 178.2 mg; calcium stearate -0.75 mg, 1.5 mg, 1.8 mg.

Description:Tablets are white or almost white in color, flat-cylindrical, with a chamfer.

Pharmacotherapeutic group:Angiotensin-converting enzyme (ACE) inhibitor

ATX: & nbsp

C.09.A.A.03 Lisinopril

C.09.A.A ACE Inhibitors

Pharmacodynamics:The ACE inhibitor reduces the formation of angiotensin II from angiotensin I. Reducing angiotensin II leads to a direct decrease in the release of aldosterone. Reduces the degradation of bradykinin and increases the synthesis of prostaglandins. Reduces the overall peripheral vascular resistance, arterial pressure (BP), preload, pressure in the pulmonary capillaries, causes an increase in the minute volume of blood and increased tolerance of the myocardium to loads in patients with chronic heart failure. Expands arteries more than veins. Some effects are explained by the effect on tissue renin-angiotensin systems. With prolonged use, myocardial hypertrophy and the walls of arteries of resistive type decrease. Improves the blood supply of the ischemic myocardium.
ACE inhibitors prolong life expectancy in patients with chronic heart failure, slow the progression of left ventricular dysfunction in patients who underwent myocardial infarction without clinical manifestations of heart failure.The antihypertensive effect begins in about 6 hours and persists for 24 hours. The duration of the effect also depends on the size of the dose. The beginning of the action is after 1 hour. The maximum effect is determined in 6-7 hours. With arterial hypertension, the effect is observed in the first days after the start of treatment, stable action develops after 1-2 months. With a sharp withdrawal of the drug, no pronounced increase in blood pressure was observed.
In addition to reducing blood pressure lisinopril reduces albuminuria. In patients with hyperglycemia contributes to the normalization of the function of the damaged glomerular endothelium.
Lizinopril does not affect the concentration of glucose in the blood in patients with diabetes mellitus and does not increase the incidence of hypoglycemia.

Pharmacokinetics:Suction. After taking the drug, about 25% of lisinopril is absorbed from the gastrointestinal tract. Eating does not affect the absorption of the drug. Bioavailability - 29%.
Distribution. Almost does not bind to blood plasma proteins. The maximum concentration in blood plasma (90 ng / ml) is achieved after 7 hours. Permeability through the blood-brain and placental barrier is low. Metabolism. Lisinopril not biotransformed in the body.
Excretion. It is excreted by the kidneys unchanged. The half-life is 12 hours.
Pharmacokinetics in selected patient groups
In patients with chronic heart failure, the absorption and clearance of lisinopril are reduced.
In patients with renal failure, the concentration of lisinopril is several times higher than the concentration in the blood plasma in volunteers, with an increase in the time to reach the maximum concentration in the blood plasma and an increase in the half-life.
In elderly patients, the concentration of the drug in the blood plasma and the area under the curve is 2 times greater than in young patients.

Indications:- Arterial hypertension (in monotherapy or in combination with other antihypertensive agents);
- Chronic heart failure (as part of combination therapy to treat patients taking digitalis and / or diuretics);
- Early treatment of acute myocardial infarction (within the first 24 hours with stable hemodynamic parameters to maintain these parameters and prevention of left ventricular dysfunction and heart failure);
- Diabetic nephropathy (insulin-dependent reduction of albuminuria in patients with normal blood pressure and insulin dependent patients with hypertension).

Contraindications:Hypersensitivity to lisinopril or other ACE inhibitors, angioedema in the anamnesis, including the use of ACE inhibitors, hereditary edema of Quincke, age under 18 years (efficacy and safety not established).

Carefully:Severe renal dysfunction, bilateral renal artery stenosis or arterial stenosis of a single kidney with progressive azotemia, condition after kidney transplantation, renal insufficiency, azotemia, hyperkalemia, aortic aortic stenosis, hypertrophic obstructive cardiomyopathy, primary hyperaldosteronism, arterial hypotension, cerebrovascular diseases (v. h. cerebral circulatory insufficiency), ischemic heart disease, coronary insufficiency, autoimmune systemic diseases will connect (including scleroderma, systemic lupus erythematosus); oppression of bone marrow hematopoiesis; diet with sodium restriction: hypovolemic conditions (incl.as a result of diarrhea, vomiting); elderly age.

Pregnancy and lactation:The use of lisinopril during pregnancy is contraindicated. When establishing a pregnancy, the drug should be stopped as soon as possible. Admission of ACE inhibitors in the 11th and III trimester of pregnancy has an adverse effect on the fetus (there may be a marked decrease in blood pressure, renal failure, hyperkalemia, skull hypoplasia, fetal death). Data on the negative effects of the drug on the fetus in case of application during the I trimester are not present. For newborns and infants who have undergone intrauterine exposure to ACE inhibitors, careful monitoring is recommended to timely detect a marked decrease in blood pressure, oliguria, and hyperkalemia.
Lizinopril penetrates the placenta. There is no data on the penetration of lisinopril into breast milk. For the period of treatment the drug should be abolished breastfeeding.

Dosing and Administration:Inside, regardless of food intake. With arterial hypertension, patients who do not receive other antihypertensives are prescribed 5 mg once a day.In the absence of effect, the dose is increased every 2-3 days by 5 mg to an average therapeutic dose of 20-40 mg / day (increasing the dose above 40 mg / day usually does not lead to a further decrease in blood pressure). 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 start of treatment, which should be taken into account when increasing the dose. With insufficient clinical effect, it is possible to combine the drug with other antihypertensive drugs.
If the patient received a preliminary treatment with diuretics, the use of these drugs should be stopped 2-3 days before the start of the use of 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, medical supervision is recommended for several hours (maximum effect is achieved after about 6 hours), since there may be a pronounced decrease in blood pressure.
With Renovascular Hypertension or other conditions with increased activity of the renin-angiotensin-aldosterone system, it is also advisable to prescribe a low initial dose of 2.5-5 mg per day, under enhanced medical supervision (control of blood pressure, kidney function, potassium concentration in serum).The maintenance dose, continuing strict medical control, should be determined depending on the dynamics of blood pressure.
With renal insufficiency due to the fact that lisinopril is released through the kidneys, the initial dose should be determined depending on the creatinine clearance, then, in accordance with the reaction, a maintenance dose should be established in conditions of frequent monitoring of kidney function, potassium level, sodium in the blood serum.

Creatinine clearance ml / min	Initial dose of mg / day
30-70	5-10
10-30	2,5-5
Less than 10	2,5

(including patients treated with hemodialysis)
With persistent arterial hypertension, prolonged maintenance therapy of 10-15 mg / day is shown.
With chronic heart failure - begin with 2.5 mg once a day, followed by an increase in the dose of 2.5 mg 3-5 days before the usual, maintaining a daily dose of 5-20 mg. The dose should not exceed 20 mg per day.
In elderly people, a more pronounced prolonged hypotensive effect is often observed, which is associated with a decrease in the rate of excretion of lisinopril (it is recommended to begin treatment with 2.5 mg / day).
Acute myocardial infarction (as part of combination therapy)
On the first day - 5 mg orally, then 5 mg every other day, 10 mg after two days and then 10 mg once a day. In patients with acute myocardial infarction, the drug should be applied for at least 6 weeks.
At the beginning of treatment or within the first 3 days after an acute myocardial infarction in patients with low systolic BP (120 mm Hg or lower), a smaller dose of 2.5 mg should be given. In the case of a decrease in blood pressure (systolic blood pressure is below or equal to 100 mm Hg), a daily dose of 5 mg can, if necessary, temporarily reduce to 2.5 mg. In the case of a long pronounced decrease in blood pressure (systolic blood pressure below 90 mm Hg for more than 1 hour), treatment with lisinopril should be discontinued.
Diabetic Nephropathy
In patients with non-insulin-dependent diabetes mellitus, 10 mg of lisinopril is administered once a day. The dose may, if necessary, be increased to 20 mg once a day in order to achieve diastolic blood pressure values below 75 mmHg. in the sitting position. In patients with insulin-dependent diabetes mellitus, the dosage is the same, in order to achieve diastolic blood pressure values below 90 mm Hg. in the sitting position.

Side effects:The most common side effects: dizziness, headache, fatigue, diarrhea, dry cough, nausea.
From the cardiovascular system: marked decrease in blood pressure, chest pain, rarely - orthostatic hypotension, tachycardia, bradycardia, worsening of symptoms of heart failure, violation of atrioventricular conduction, myocardial infarction, heart palpitations.
From the central nervous system: lability of mood, confusion, paresthesia, drowsiness, convulsive twitching of the muscles of the limbs and lips, rarely - asthenic syndrome.
On the part of the hematopoiesis system: leukopenia, neutropenia, agranulocytosis, thrombocytopenia, anemia (decrease in the concentration of hemoglobin, hematocrit, erythrocytopenia).
Laboratory indicators: hyperkalemia, hyponatremia, rarely - increased activity of "hepatic" enzymes, hyperbilirubinemia, increased levels of urea and creatinine.
From the respiratory system: dyspnea, bronchospasm.
From the digestive tract: dry mouth, anorexia, dyspepsia, changes in taste, abdominal pain, pancreatitis, hepatocellular or cholestatic jaundice, hepatitis.
From the skin: urticaria, increased sweating, pruritus, alopecia, photosensitivity.
From the genitourinary system: impaired renal function, oliguria, anuria, acute renal failure, uremia, proteinuria, decreased potency.
Allergic reactions: angioedema, edema of the face, extremities, lips, tongue, epiglottis and / or larynx, skin rashes, itching, fever, positive results of the test for antinuclear antibodies, increased erythrocyte sedimentation rate (ESR), eosinophilia, leukocytosis. In very rare cases - interstitial angioedema.
Other: myalgia, arthralgia / arthritis, vasculitis.

Overdose:Symptoms (occur when taking a single dose of 50 mg and above): a marked decrease in blood pressure; dry mouth, drowsiness, urinary retention, constipation, anxiety, increased irritability.
Treatment: symptomatic therapy, intravenous fluid administration, control of blood pressure, water-electrolyte balance and normalization of the latter.
Lizinopril can be removed from the body by hemodialysis.

Interaction:Lisinopril reduces the excretion of potassium from the body when treated with diuretics.
Special care is required when using the drug simultaneously with:
- potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium, salt substitutes containing potassium (increases the risk of hyperkalemia, especially with impaired renal function), so they can be jointly administered only on the basis of an individual decision of the treating doctor with regular monitoring of serum potassium and kidney function .
Cautiously can be applied together:
with diuretics: with the additional administration of a diuretic to a patient receiving Lisinopril, as a rule, the additive antihypertensive effect comes with the risk of a marked decrease in blood pressure; with other antihypertensive agents (additive effect); with non-steroidal anti-inflammatory drugs (indomethacin and others), estrogens, as well as adrenostimulators - a decrease in the antihypertensive effect of lisinopril;
with lithium (liberation of lithium may decrease, therefore, the concentration of lithium in serum should be monitored regularly);
with antacids and colestyramine - reduce absorption in the gastrointestinal tract.
Alcohol enhances the effect of the drug.

Special instructions:Symptomatic hypotension
Most often, a marked decrease in blood pressure occurs with a decrease in the volume of fluid caused by diuretic therapy, a decrease in the amount of salt in the diet, dialysis, diarrhea, or vomiting. In patients with chronic heart failure with simultaneous renal insufficiency or without it, a marked decrease in blood pressure is possible. It is more often detected in patients with a severe stage of chronic heart failure, as a result of the use of large doses of diuretics, hyponatremia or impaired renal function. In such patients, treatment with lisinopril should be started under the strict supervision of a doctor (with care to select a dose of the drug and diuretics).
Similar rules should be adhered to when assigning patients with coronary heart disease, cerebrovascular insufficiency, in which a sharp decrease in blood pressure can lead to myocardial infarction or stroke.
Transient hypotensive reaction is not a contraindication for taking the next dose of the drug.
With the use of lisinopril in some patients with chronic heart failure, but with normal or low blood pressure, there may be a decrease in blood pressure, which is usually not the reason for discontinuing treatment.
Before starting treatment with lisinopril, if possible, normalize the sodium concentration and / or replace lost fluid, carefully monitor the effect of the initial dose of lisinopril on the patient.
In the case of stenosis of the renal artery (especially with bilateral stenosis, or in the presence of stenosis of the artery of a single kidney), as well as inadequate circulation due to lack of sodium and / or liquid, the use of lisinopril can lead to impaired renal function, acute renal failure, which usually is irreversible after drug discontinuation.
With acute myocardial infarction
The use of standard therapy (thrombolytics, acetylsalicylic acid, beta-blockers). Lisinopril it is possible to use together with intravenous administration or with the use of therapeutic transdermal systems of nitroglycerin.
Surgery / general anesthesia
With extensive surgical interventions, as well as with the use of other drugs that cause a decrease in blood pressure, lisinopril, blocking the formation of angiotensin II, can cause a pronounced unpredictable decrease in blood pressure.
In elderly patients, the same dose leads to a higher concentration of the drug in the blood, therefore special caution is required when determining the dose.
Because the potential risk of agranulocytosis can not be ruled out, periodic monitoring of the blood picture is required. When the drug is used in dialysis with a polyacryl-nitrile membrane, anaphylactic shock can occur, so either a different type of dialysis membrane or other antihypertensive agents is recommended.

Effect on the ability to drive transp. cf. and fur:There is no data on the effect of lisinopril on the ability to drive vehicles and mechanisms, applied in therapeutic doses, but it must be borne in mind that dizziness may occur, therefore, care must be taken.

Form release / dosage:Tablets of 5, 10 or 20 mg.

Packaging:10 tablets per contour cell packaging made of polyvinylchloride film and aluminum foil.
For 30 or 100 tablets in a can of polymer or a bottle of polymer. Each jar or bottle, 2, 3, 5, 6 contour mesh packages together with the instruction for use is placed in a cardboard box.

Storage conditions:In a dry, the dark place at a temperature of no higher than 25 ° C.
Keep out of the reach of children.

Shelf life:3 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-004504/07

Date of registration:06.12.2007 / 21.07.2016

Expiration Date:Unlimited

The owner of the registration certificate:NORTH STAR, CJSC NORTH STAR, CJSC Russia

Manufacturer: & nbsp

NORTH STAR, CJSC Russia

Information update date: & nbsp2016-11-23

Illustrated instructions

Instructions

Lizinopril-SZ (Lisinopril SZ)