Active substanceLisinoprilLisinopril
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  • Dosage form: & nbsppills
    Composition:

    One tablet, with a dosage of 5 mg, contains:

    active substance: lisinopril dihydrate - 5.44 mg (in terms of lisinopril - 5.00 mg);

    Excipients: potato starch - 20,00 mg; cellulose microcrystalline - 6.50 mg; stearic acid - 1.00 mg; Povidone (polyvinylpyrrolidone) - 1.00 mg; lactose monohydrate - 66,06 mg.

    One tablet, with a dosage of 10 mg, contains:

    active substance: lisinopril dihydrate 10.88 mg (in terms of lisinopril - 10.00 mg);

    Excipients: potato starch - 20,00 mg; cellulose microcrystalline - 6.50 mg; stearic acid - 1.00 mg; Povidone (polyvinylpyrrolidone) - 1.00 mg; lactose monohydrate - 60.62 mg.

    Description:Round flat cylindrical tablets of white color with a facet and a risk. Tablets with a dosage of 5 mg have an engraving "5".
    Pharmacotherapeutic group:Angiogenesin-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 prostaglandin (Pg). Reduces the overall peripheral vascular resistance (OPSS), arterial pressure (BP), preload, pressure in the pulmonary capillaries, causes an increase in the minute volume of blood (IOC) and an increase in myocardial tolerance to loads in patients with chronic heart failure (CHF). Expands arteries more than veins.Some of the effects are explained by exposure to tissue renin-angiotensin-aldosterone system (RAAS). 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 CHF, slow the progression of left ventricular dysfunction (LV) in patients who underwent myocardial infarction without clinical manifestations of heart failure.

    The onset of action is after 1 hour. The maximum effect is determined 6-7 hours after ingestion, duration is 24 hours. With arterial hypertension, the effect is observed in the first days after the start of treatment, stable effect develops after 1-2 months of therapy.

    Pharmacokinetics:

    Absorption - 30% (6-60%); bioavailability is 25%. Poorly binds to blood plasma proteins. The permeability through the blood-brain barrier (BBB) ​​and the placental barrier is low. The maximum concentration in blood plasma - about 90 ng / ml is achieved after 7 hours.

    Metabolism is practically not exposed and excreted by the kidneys unchanged. The period of semirecession is 12 hours.The permeability through the BBB and the placental barrier is low.

    Indications:

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

    - Chronic heart failure (as part of combination therapy to treat patients taking cardiac glycosides and / or diuretics);

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

    - Diabetic nephropathy (decrease in albuminuria in patients with type 1 diabetes mellitus with normal BP, and patients with type 2 diabetes mellitus with arterial hypertension).

    Contraindications:

    - Hypersensitivity to lisinopril and other components of the drug, as well as to other ACE inhibitors;

    - angioedema in the anamnesis, incl. on the background of the use of ACE inhibitors;

    - Hereditary edema Quincke or idiopathic angioedema;

    - galactose intolerance, lactase deficiency, glucose-galactose malab-sorption syndrome;

    - age under 18 years (effectiveness and safety not established);

    - pregnancy (see section "Application during pregnancy and during breast-feeding");

    - the period of breastfeeding (see the section on "Application during pregnancy and during breastfeeding");

    - simultaneous use with aliskiren and aliskirenoderzhaschimi drugs in patients with diabetes mellitus or impaired renal function (glomerular filtration rate (GFR) <60 ml / min / 1.73 m2) (see the sections "Special instructions" and "Interaction with other medicinal products").

    Carefully:Severe renal dysfunction, bilateral renal artery stenosis or arterial stenosis of a single kidney with progressive azotemia, condition after kidney transplantation, azotemia, hyperkalemia, aortic stenosis / mitral stenosis / hypertrophic obstructive cardiomyopathy, primary hyperaldosteronism, arterial hypotension, cerebrovascular diseases (including cerebral circulatory insufficiency), coronary heart disease, CHF, autoimmune systemic connective tissue diseases (incl.scleroderma, systemic lupus erythematosus); oppression of bone marrow hematopoiesis; diet with restriction of table salt; hypovolemic conditions (including as a result of diarrhea, vomiting); old age, hemodialysis using high-permeability dialysis membranes with high permeability, simultaneous use of potassium-sparing diuretics, potassium preparations, potassium-containing substitutes for dietary salt and lithium, diabetes mellitus, surgical intervention / general anesthesia, desensitizing therapy, low density lipoprotein apheresis (LDL) patients Negroid race.
    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 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 effects of lisinopril on the fetus in case of application during the I trimester "no.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 isolation of lisinopril in breast milk. If taking the drug is necessary during lactation, then breastfeeding should be canceled.

    Dosing and Administration:

    Inside, once a day in the morning, regardless of food intake, preferably at the same time.

    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, simultaneous use with other antihypertensive agents is possible.

    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 possible, 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 (the maximum effect is reached after about 6 hours), since there may be a pronounced decrease in blood pressure.

    In chronic heart failure: the initial dose is 2.5 mg per day (recommended lisinopril in tablets of 2.5 mg), with a gradual increase in 3-5 days to 5-10 mg per day. The maximum daily dose is 20 mg.

    Acute myocardial infarction (as part of combination therapy): in the first 24 hours - 5 mg, then 5 mg every other day, 10 mg after two days and then 10 mg once a day. The course of treatment - at least 6 weeks.

    When Renovascular hypertension or other conditions with increased activity of RAAS, it is also advisable to prescribe a low initial dose of 5 mg per day, under enhanced medical supervision (control of blood pressure, renal function, potassium ion content in the blood 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 the initial dose should be determined depending on the creatinine clearance. Further, the selection of doses should be made depending on individual reactions with regular monitoring of kidney function, potassium, sodium in the blood serum.

    Creatinine clearance ml / min

    Initial dose of mg / day

    30-70

    5-10

    10-30

    5

    (including patients on hemodialysis)

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

    Diabetic Nephropathy: In patients with type 2 diabetes mellitus, 10 mg of Lysinopril 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 1 diabetes mellitus, the dose is the same, in order to achieve diastolic blood pressure values ​​below 90 mm Hg. in the "sitting" position.

    Side effects:

    The incidence of side effects is characterized as often (≥1%), rarely (<1%).

    The most common side effects: dizziness, headache, fatigue, diarrhea, dry cough, nausea.

    From the cardiovascular system: often - marked decrease in blood pressure, orthostatic hypotension: rarely - chest pain, tachycardia, bradycardia, aggravation of symptoms of chronic heart failure, violation of atrioventricular conduction. myocardial infarction.

    From the central nervous system: often - paresthesia, lability of mood, confusion, drowsiness, convulsive twitching of the muscles of the extremities and lips, rarely asthenic syndrome.

    From the hematopoiesis: rarely - leukopenia, neutropenia, agranulocytosis, thrombocytopenia, with long-term treatment - anemia (reduction of hemoglobin, hematocrit, erythropenia).

    From the respiratory system: rarely shortness of breath, bronchospasm.

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

    From the skin: rarely - urticaria, pruritus, increased sweating, alopecia, photosensitivity.

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

    Laboratory indicators: often - hyperkalemia.hyponatremia; rarely - hyperbilirubinemia, increased activity of "hepatic" enzymes, hypercreatininaemia, increased concentrations of urea and creatinine.

    Allergic reactions: rarely - angioedema, swelling of the face, limbs, lips. tongue, epiglottis and / or larynx, skin rashes, itchy skin, fever, false positive antinuclear antibody test results, increased erythrocyte sedimentation rate (ESR), eosinophilia, leukocytosis. In rare cases - intestinal angioedema.

    Other: rarely - arthralgia / arthritis, vasculitis, myalgia.

    If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

    Overdose:

    Symptoms (occur when taking a single dose of 50 mg): marked decrease in blood pressure, dryness of the oral mucosa, drowsiness, urinary retention, constipation, anxiety, increased irritability.

    Treatment: there is no specific antidote. Symptomatic therapy. Gastric lavage, application of enterosorbents and laxatives.Intravenous introduction of 0.9% sodium chloride solution was shown. In the case of a sustained bradycardia, the use of an artificial pacemaker is necessary. It is necessary to monitor blood pressure, indicators of water-electrolyte balance. Hemodialysis is effective.

    Interaction:

    With the simultaneous use of the drug with potassium-sparing diuretics (spironolactone, its derivative - eplerenone, Triamterene, amiloride), potassium preparations, salt substitutes containing potassium, cyclosporin increased risk of hyperkalemia, especially with impaired kidney function and therefore can be used only in conjunction with regular monitoring the potassium content in blood serum and renal function.

    The simultaneous use of beta-blockers, blockers "slow" calcium channel (BCCI), diuretics, tricyclic antidepressants / neuroleptics and other antihypertensive agents enhances the antihypertensive action.

    Lizinopril slows down the excretion of lithium preparations. Therefore, when combined, it is necessary to regularly monitor the concentration of lithium in the blood serum. Antacids and colestramine reduce the absorption of lisinopril in the gastrointestinal tract (GIT).

    Hypoglycemic agents (insulin, hypoglycemic agents for oral administration)

    The use of DFT inhibitors can enhance the hypoglycemic effect of insulin and hypoglycemic agents for oral administration until the development of hypoglycemia. As a rule, this is observed in the first weeks of simultaneous therapy and in patients with impaired renal function.

    Non-steroidal anti-inflammatory drugs (PPVP) (including selective inhibitors of cyclooxygenase-2 (COX-2)), estrogens, adrenomimetics reduce the antihypertensive effect of lisinopril. The simultaneous use of ACE inhibitors and PPVP may lead to impaired renal function, including the development of acute renal failure, and an increase in potassium in the blood serum, especially in patients with reduced renal function. Care should be taken when prescribing this combination, especially in elderly patients. Patients should receive an adequate amount of fluid, and it is recommended that the kidney function be carefully monitored, both at the beginning and during the treatment.

    With simultaneous use of ACE inhibitors and preparations of gold intravenously (sodium aurotomy malate) describes a symptom complex, which includes facial flushing, nausea, vomiting and lowering blood pressure.

    Co-administration with selective serotonin reuptake inhibitors can lead to severe hyponatraemia.

    Joint application with allopurinol, procainamide, cytostatics can lead to leukopenia.

    Double blockade of RAAS

    In the literature it was reported that in patients with established atherosclerotic disease, heart failure or diabetes mellitus with damage to target organs. simultaneous therapy with an ACE inhibitor and angiotensin II receptor antagonists (APAII) is associated with a higher incidence of arterial hypotension, syncope, hyperkalemia, and impaired renal function (including acute renal failure) compared with the use of only one drug that affects RAAS. Double blockade (for example, with the combination of an ACE inhibitor with APAII) should be limited to individual cases with careful monitoring of kidney function, potassium and blood pressure.

    Simultaneous use is contraindicated (cm.section "Contraindications")

    Aliskiren

    In patients with diabetes mellitus or renal dysfunction (GFR less than 60 ml / min / 1.73 m2) increases the risk of hyperkalemia, worsening kidney function and increasing the incidence of cardiovascular morbidity and mortality.

    Estramustine

    Simultaneous application can lead to an increased risk of side effects, such as angioedema.

    Baclofen

    Strengthens the antihypertensive effect of ACE inhibitors. You should carefully monitor blood pressure and, if necessary, dosage of antihypertensive drugs.

    Glyptins (linaglyptin, siksagliptin, sitagliptin, vitagliptin)

    Co-administration with ACE inhibitors may increase the risk of developing angioedema due to suppression of dipeptidyl peptidase IV (DPP-IV) activity with glyptin.

    Sympathomimetics

    May weaken the antihypertensive effect of ACE inhibitors.

    Tricyclic antidepressants, antipsychotics (antipsychotics) and means for general anesthesia

    Simultaneous use with ACE inhibitors can lead to an increase in antihypertensive action (see section "Special instructions").

    Special instructions:

    Symptomatic arterial hypotension

    Most often, a marked decrease in blood pressure occurs with a decrease in the volume of circulating blood (BCC), caused by diuretic therapy, a decrease in the amount of salt in the poor, dialysis, diarrhea, or vomiting. In patients with chronic heart failure with concurrent renal failure or without it, a marked decrease in blood pressure is possible.

    Under the strict supervision of a doctor, Lisinopril patients with coronary artery disease, cerebrovascular insufficiency, in whom a sharp decrease in blood pressure can lead to myocardial infarction or to a stroke.

    Transient arterial hypotension is not a contraindication for taking the next dose of the drug. In the case of development of arterial hypotension the patient should be transferred to the "lying" position with raised legs. If necessary, BCC should be filled with intravenous 0.9% sodium chloride solution. Transient arterial hypotension is not an obstacle for further administration of the drug. After the recovery of bcc and blood pressure, treatment can be continued.

    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 the reason for discontinuing treatment.

    Before the start of treatment with the drug, if possible, normalize the sodium content and / or make up the BCC, carefully monitor the effect of the initial dose of lisinopril on the patient.

    In the case of stenosis of the renal arteries (in particular, 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, It is irreversible even after the drug is discontinued.

    Hyperkalemia

    Hyperkalemia can develop during treatment with ACE inhibitors, including, and lisinopril. Risk factors for hyperkalemia are renal failure, decreased kidney function, age over 70 years, diabetes mellitus, some concomitant conditions (dehydration, acute heart failure, metabolic acidosis).simultaneous intake of potassium-sparing diuretics (such as spironolactone and its derivative eplerenone, triamterene, amiloride), food additives / potassium preparations or potassium-containing substitutes for edible salt, and the use of other drugs. contributing to increased potassium levels in the blood (eg, heparin). The use of dietary supplements / potassium preparations, potassium-sparing diuretics, potassium-containing substitutes for edible salt can lead to a significant increase in potassium in the blood, especially in patients with reduced renal function. Hyperkalemia can lead to serious, sometimes fatal heart rhythm disturbances. If simultaneous use of lisinopril and the above drugs is required, treatment should be carried out with caution in the context of regular monitoring of serum potassium content (see section "Interaction with other medicinal products").

    Mitral stenosis / aortic stenosis / hypertrophic obstructive cardiomyopathy

    Liziopril, like other ACE inhibitors, should be administered with caution to patients with obstruction of the left ventricular outflow tract (aortic stenosis,hypertrophic obstructive cardiomyopathy), as well as patients with mitral stenosis.

    With acute myocardial infarction

    The use of standard therapy (thrombolytics, acetylsalicylic acid as an antiplatelet agent, beta-address 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.

    With the development of arterial hypotension, blood pressure should be maintained by replenishing the BCC. It is necessary to alert the surgeon / anesthesiologist that the patient is taking ACE inhibitors.

    In elderly patients the same dose leads to a higher concentration of lisinopril in the blood, therefore special caution is required when determining the dose.

    Hemodialysis

    In patients on hemodialysis using high-permeability membranes (for example, AN69®), cases of anaphylactic reactions have been observed against the background of ACE inhibitor therapy.The use of ACE inhibitors should be avoided when using this type of membrane.

    Neutropenia / agranulocytosis / thrombocytopenia / anemia

    Against the background of taking ACE inhibitors, neutropenia / agranulocytosis, thrombocytopaediasis and anemia can occur. In patients with normal renal function and with the presence of other aggravating factors, neutropenia develops rarely. With particular caution, Lysioopril should be used in patients with systemic connective tissue diseases, when immunosuppressants, allopurinol or Irokainamide are used, especially in patients with impaired renal function.

    Some patients had severe infections, in some cases, resistant to intensive antibiotic therapy. In the appointment of lisinopril, it is recommended that such patients periodically check the white blood cell count. Patients should inform the doctor of any signs of infectious diseases (eg, sore throat, fever).

    Anaphylactoid reactions during apheresis of low density lipoproteins (LDL)

    In rare cases, patients receiving inhibitors of AG1F, during the procedure of apheresis of LDL with the use of dskstrane sulfate, life-threatening anaphylactoid reactions can develop.To prevent anaphylactoid reaction, therapy with an ACE inhibitor should be temporarily discontinued before each apheresis procedure.

    Anaphylactoid reactions during desensitization

    There are some reports of the development of anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy, for example, by the venom of Hymenoptera. ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. The use of ACE inhibitors should be avoided for patients receiving immunotherapy with bee venom. However, this reaction can be avoided by the temporary withdrawal of the ACE inhibitor before the desensitization procedure begins.

    Hypersensitivity / angioedema

    When taking ACE inhibitors, including lisinopril, in rare cases and in any period of therapy, development of an angioedema of the face, upper and lower extremities, lips, mucous membranes, tongue, vocal cords and / or larynx can be observed (see "Side act").When symptoms appear, taking the drug should be stopped immediately, and the patient should be observed until the signs of edema disappear completely. If the swelling affects only the face and lips, then its manifestations usually pass on their own, although antihistamines can be used to treat the symptoms.

    Angioedema, accompanied by swelling of the larynx, can lead to death. Swelling of the tongue, vocal cords, or larynx can lead to airway obstruction. When these symptoms appear, urgent therapy is required, including subcutaneous injection of epinephrine (adrenaline) and / or providing airway patency. The patient should be under medical supervision until the symptoms disappear completely and persistently.

    Patients with a history of Quinck's edema who are not associated with taking ACE inhibitors may be at increased risk of developing this drug when taking this drug (see "Contraindications").

    In rare cases, against the background of therapy with ACE inhibitors, angioedema develops in the intestine. In this case, patients have abdominal pain as an isolated symptom or in combination with nausea and vomiting,in some cases without a prior angioedema and at a normal level of C1-esterase. The diagnosis was established using computed tomography of the abdominal region, ultrasound examination or surgical intervention. Symptoms disappeared after discontinuation of ACE inhibitors. Therefore, patients with abdominal pain receiving ACE inhibitors should take into account the possibility of angioedema edema development during differential diagnosis (see section "Side effect").

    Kidney Transplantation

    Data on the use of the drug Lisinopril in patients after kidney transplantation there are no kidneys.

    Ethnic differences

    It should be borne in mind that in patients of the Negroid race the risk of angioedema development is higher. Like other ACE inhibitors, Lisinopril It is less effective in reducing blood pressure in patients of the Negroid race.

    This effect is probably associated with a marked predominance of low-grade status in patients of the Negroid race with arterial hypertension.

    Impaired liver function

    In rare cases, when taking ACE inhibitors, there was a syndrome of cholestatic jaundice withtransition to fulminant liver necrosis, sometimes with a fatal outcome. The mechanism of development of this syndrome is unclear. If there is jaundice or a significant increase in the activity of "liver" enzymes against the background of taking ACE inhibitors, you should stop taking the drug (see the "Side effect" section), the patient should be under appropriate medical supervision.

    Double blockade of RAAS

    Arterial hypotension, fainting, stroke, hyperkalemia and renal dysfunction (including acute renal failure) have been reported in susceptible patients, especially when used with medications that affect this system. Therefore, a double blockade of RAAS due to a combination of an ACE inhibitor with ARAII or aliskiren is not recommended.

    The combination with aliskiren is contraindicated in patients with diabetes mellitus or renal dysfunction (GFR <60 ml / min / 1.73 m2) (see the sections "Contraindications" and "Interaction with other medicinal products").

    Patients with diabetes mellitus

    When prescribing a drug for patients with diabetes mellitus receiving hypoglycemic agents for ingestion or insulin, during the first month of therapy it is necessary to regularly monitor the concentration of glucose in the blood (see.section "Interaction with other medicinal products").

    Effect on the ability to drive transp. cf. and fur:Lisinopril should be used with caution for patients who manage motor vehicles and engaged in activities that require increased concentration of attention and quick reaction, due to the danger of developing arterial hypotension and dizziness.
    Form release / dosage:Tablets 5 and 10 mg.
    Packaging:For 10 tablets in a planar cell package. 2, 3 contour mesh packages together with instructions for medical use are placed in a pack of cardboard.
    Storage conditions:

    In a place protected from light and moisture, at a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:2 years. The drug can not be used beyond the time specified on the package.
    Terms of leave from pharmacies:On prescription
    Registration number:LP-002961
    Date of registration:21.04.2015 / 14.07.2016
    Expiration Date:21.04.2020
    The owner of the registration certificate:BORISOVSKIY FACTORY OF MEDPREPARATES, OJSC BORISOVSKIY FACTORY OF MEDPREPARATES, OJSC Republic of Belarus
    Manufacturer: & nbsp
    Information update date: & nbsp25.02.2018
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