Lizinopril - instructions for use, dose, side effects, contraindications

active substance: lisinopril dihydrate - 10.888 mg (equivalent to 10 mg of lisinopril - anhydrous), Excipients: ludistress (lactose monohydrate, povidone, crosspovidone) - 137.612 mg, calcium stearate - 1.50 mg.

Description:Round, biconvex tablets are white or almost white in color.

Pharmacotherapeutic group:Angiotensin-converting enzyme inhibitor

ATX: & nbsp

C.09.A.A.03 Lisinopril

C.09.A.A ACE Inhibitors

Pharmacodynamics:

The angiotensin-converting enzyme (ACE) inhibitor reduces the formation of angiotensin II from angiotensin I. Reducing angiotensin II leads to a direct reduction 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-aldosterone 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 onset of action is after 1 hour. The maximum antihypertensive effect is determined after approximately 6 to 7 hours and persists for 24 hours. The duration of the effect also depends on the size of the dose. 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 blood glucose 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. Absorption is on average 30%, bioavailability is 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 insufficiency, concentrations of lisinopril several times prevail in blood plasma concentrations in healthy 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 concentration-time curve (AUC) is 2 times greater than in young patients.

Indications:

- Arterial hypertension (in monotherapy or in combination with other antihypertensive drugs);

- Chronic heart failure (as part of combination therapy);

- Early treatment of acute myocardial infarction (as part of combination therapy,in the first 24 hours with stable parameters of hemodynamics to maintain these parameters and prevention of left ventricular dysfunction and heart failure);

Diabetic nephropathy (decrease in albuminuria in patients with type I diabetes with normal BP and patients with type II diabetes with arterial hypertension).

Contraindications:Hypersensitivity to lisinopril, drug auxiliaries, other ACE inhibitors, angioedema in history, including the use of ACE inhibitors, hereditary edema of Quincke, idiopathic angioedema, lactose intolerance, lactase deficiency, glucose-galactose malabsorption, pregnancy, lactation , age to 18 years (efficacy and safety not established).

Carefully:Severe renal dysfunction, bilateral stenosis of the renal arteries or stenosis of the single kidney artery with. progressive azotemia, condition after kidney transplantation, renal failure, azotemia, hyperkalemia, aortic aortic stenosis, hypertrophic obstructive cardiomyopathy, primary hyperaldosteronism, arterial hypotension, cerebrovascular diseases (incl.cerebral circulatory insufficiency), ischemic heart disease, coronary insufficiency, autoimmune systemic connective tissue diseases (including scleroderma, systemic lupus erythematosus); oppression of bone marrow hematopoiesis; diet with restriction of table salt; hypovolemic conditions (including as a result of diarrhea, vomiting); hemodialysis using high-permeability dialysis membranes with high permeability (AN69®), advanced age.

Pregnancy and lactation:

Use of the medicinal product Lisinopril in pregnancy is contraindicated. When establishing pregnancy, taking the drug should be stopped as soon as possible. Admission of ACE inhibitors in the II and III trimester of pregnancy has an adverse effect on the fetus (there may be a marked decrease in blood pressure, renal failure, hyperkalemia, hypoplasia of the skull bones, fetal death). Data on the negative effect of lisinopril 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. Lisinopril penetrates the placenta.There is no data on excretion of lisinopril in breast milk. For the period of drug treatment Lisinopril it is necessary to abolish 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 taking of such drugs should be stopped 2 to 3 days before 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.

In the case of renovascular hypertension or other conditions with an increased activity of the renin-angiotensin-aldosterone system, it is also advisable to prescribe a low initial dose of 2.5 to 5 mg per day under regular medical supervision (blood pressure control, kidney function, potassium content in blood serum). The maintenance dose, continuing strict medical control, should be determined depending on the dynamics of blood pressure.

With renal failure due to the fact that lisinopril is released through the kidneys, the initial dose should be determined depending on the creatinine clearance. Then, according to the reaction, a maintenance dose should be established in conditions of frequent monitoring of renal function, potassium content, 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 (including patients treated with hemodialysis)	2,5

With persistent arterial hypertension, prolonged maintenance therapy of 10-15 mg / day is shown.

With ironic heart failure - begin with 2.5 mg 1 time per day with a subsequent increase in the dose by 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 antihypertensive 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), the drug should be discontinued.

Diabetic nephropathy. In patients with type 1 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 type II diabetes, the dosage of the drug is the same (10 mg once a day), in order to achieve diastolic blood pressure values below 90 mm Hg. in the "sitting" position.

If it is necessary to apply the minimum doses (2.5 mg and 5 mg) to ensure the correct dosage regimen, other drugs of lisinopril in the dosage form of the 2.5 mg tablet or 5 mg tablet should be taken with a risk.

Side effects:

Frequency of side effects: very often (1/10 or more); often (1/100 or more, less than 1/10); infrequently (1/1000 and more, less than 1/100); rarely (1/10000 or more, less than 1/1000), very rarely (less than 1/10000).

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

From the immune system: infrequently (0.1%) - angioedema (face, lips, tongue, larynx or epiglottis, upper and lower extremities), photosensitization; rarely - interstitial angioedema (edema of the interstitial tissue of the lungs without exit of the transudate into the lumen of the alveoli), a syndrome including acceleration of the erythrocyte sedimentation rate (ESR), the appearance of antinuclear antibodies.

From the cardiovascular system: often - marked decrease in blood pressure, orthostatic hypotension; infrequent - heart rhythm disturbances, tachycardia, bradycardia, aggravation of symptoms of chronic heart failure, chest pain; rarely - palpitations, myocardial infarction, cerebrovascular stroke in patients with an increased risk of the disease, due to a pronounced decrease in blood pressure.

From the central nervous system: often - increased fatigue, drowsiness; infrequently - paresthesia, convulsive twitching of the muscles of the limbs and lips; rarely - asthenia, lability of mood, confusion.

On the part of the hematopoiesis system: infrequently - leukopenia, neutropenia, agranulocytosis, thrombocytopenia, with long-term treatment, a small decrease in the concentration of hemoglobin and hematocrit, erythrocytopenia.

From the respiratory system: dry cough, shortness of breath, bronchospasm.

Laboratory indicators: hyperkalemia, hyponatremia, hypercreatininemia, azotemia, hyperuricemia, hyperbilirubinemia, increased activity of "liver" enzymes, especially in the presence of a history of kidney disease, diabetes, and renovascular hypertension.

From the digestive system: rarely - dryness of the oral mucosa, anorexia, dyspepsia, changes in taste, abdominal pain, pancreatitis, hepatocellular or cholestatic jaundice, hepatitis.

From the skin: rare - urticaria, increased sweating, pruritus, alopecia, Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome).

From the urinary system: rarely - a violation of kidney function, oliguria, anuria, acute renal failure, uremia, proteinuria.

Other: myalgia, vasculitis, arthralgia, fever, decreased potency, impaired fetal development.

Overdose:

Symptoms: pronounced - decrease in blood pressure, dryness of the oral mucosa, drowsiness, urinary retention, constipation, anxiety, increased irritability.

Treatment: symptomatic therapy, intravenous administration, fluids, blood pressure control, monitoring and normalization of the water-electrolyte balance.

Lizinopril can be removed from the body by hemodialysis.

Interaction:

Special care is required when using the medicinal product at the same time:

- with potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium, salt substitutes containing potassium (the risk of hyperkalemia increases, especially with impaired renal function; therefore, they can be jointly administered only on the basis of an individual decision of the treating physician with regular monitoring of serum potassium and kidney function);

- with simultaneous use with preparations of gold intravenously (sodium aurotomy malate) there may be a symptom complex, which includes facial flushing, nausea, vomiting and a decrease in blood pressure;

- simultaneous reception of the drug with insulin, as well as oral hypoglycemic drugs can lead to the development of hypoglycemia. The greatest risk of development is observed during the first weeks of combination therapy, as well as in patients with impaired renal function. Patients with diabetes require careful monitoring of glycemia, especially during the first month of therapy with an ACE inhibitor;

- combined use of the drug with beta-blockers, slow calcium channel blockers (BCCI), diuretics, tricyclic antidepressants / antipsychotics and other antihypertensive drugs, increases the severity of hypotensive action;

- when the drug is used together with selective serotonin reuptake inhibitors, pronounced hyponatraemia may occur;

- Joint use with allopurinol, procainamide, cytostatics can lead to leukopenia.

Lizinopril can be applied with caution together:

- with diuretics: with additional administration of a diuretic to a patient receiving Lisinopril, as a rule, there is an additive, antihypertensive effect - the risk of a pronounced 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 can decrease, therefore it is necessary to regularly monitor the lithium content in blood serum);

- with antacids and colestyramine - reduced absorption of lisinopril 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 circulating fluid caused by diuretic therapy, a decrease in table salt in the diet, dialysis, diarrhea, or vomiting.

Based on the results of epidemiological studies, it is assumed that simultaneous administration of angiotensin-converting enzyme and insulin inhibitors, as well as hypoglycemic agents for oral administration, may lead to the development of hypoglycemia. The highest risk is observed during the first weeks of combined therapy, as well as in patients with impaired renal function. Patients with diabetes require careful monitoring of glycemia, especially during the first month of therapy with an angiotensin-converting enzyme inhibitor.

In patients with chronic heart failure with simultaneous renal failure 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 consequence 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 appointing patients with ischemic 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 1 dose of the next dose of the drug.

When using 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 a reason for stopping treatment.

Before starting treatment with lisinopril, if possible, normalize the sodium content and / or replenish the lost volume of the circulating fluid. It is necessary to carefully control the first dose of lisinopril.

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 is usually 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.

In patients taking the drug, during desensitization to the hymenoptera, the emergence of a life threatening anaphylactoid reaction is extremely rare. It is necessary to temporarily stop the drug treatment before starting the course of desensitization.

In rare cases, when taking the drug during apheresis of low-density lipoproteins, an anaphylactoid reaction may develop. To prevent the development of such reactions, you must cancel the drug before each apheresis procedure.

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 recommended therapeutic dose may lead to higher concentrations of the drug in the blood, so special care 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, therefore, it is recommended that either a different type of membrane for dialysis or the appointment of other antihypertensive agents.

Effect on the ability to drive transp. cf. and fur:There is no evidence of the effect of lisinopril on management, vehicles and mechanisms used in therapeutic doses, but it should be borne in mind that dizziness may occur, so be careful.

Form release / dosage:Tablets of 10 mg.

Packaging:

10 tablets are packed in a contour mesh box made of a polyvinylchloride film and aluminum foil printed lacquered. For 1, 2, 3 or 5 contour packagings together with the instructions for use are placed in a cardboard box.

Packing for hospitals. For 100,200, 300,400 or 500 contour squares with instructions for use are placed in carton boxes.

For 500, 1000 or 2000 tablets are packed in polymer cans with lids made of polymer materials. For 1, 2, 3, 4, 5 or 6 cans with instructions for use are put in boxes of cardboard.

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:2 years. The drug should not be used after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LS-000779

Date of registration:29.11.2011

Expiration Date:Unlimited

The owner of the registration certificate:ZIO-HEALTH, JSC ZIO-HEALTH, JSC Russia

Manufacturer: & nbsp

ZIO-HEALTH, JSC Russia

Information update date: & nbsp25.02.2018

Illustrated instructions

Instructions

Lisinopril (Lisinopril)