Description
Release form
tablets
Pharmacological action of
ATC code: C09AA03
Pharmacological action of
Pharmacodynamics
ACE inhibitor, reduces the formation of angiotensin II from angiotensin I reduction aldosterone. Reduces the degradation of bradykinin and increases the synthesis of prostaglandins. Reduces total peripheral vascular resistance (OPSS), blood pressure (BP), preload, pressure in the pulmonary capillaries, causes an increase in minute blood volume (IOC) and an increase in myocardial tolerance to stress in patients with chronic heart failure (CHF). Expands arteries to a greater extent than veins. Some effects are explained by the effect on the tissue renin-angiotensin-aldosterone system (RAAS). With prolonged use, hypertrophy of the myocardium and walls of the arteries of the resistive type decreases. Improves blood supply to the ischemic myocardium.
ACE inhibitors lengthen life expectancy in patients with heart failure, slow the progression of left ventricular dysfunction (LV) in patients after myocardial infarction without clinical manifestations of heart failure (HF).
The onset of antihypertensive action – after 1 hour. The maximum effect is observed after 6-7 hours. The antihypertensive effect 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, a stable effect develops after 1-2 months.
Pharmacokinetics
The average degree of absorption of lisinopril is about 25%, with significant interindividual variability (6-60%). Food does not affect the absorption of lisinopril.
The maximum plasma concentration of about 90 ng / ml is reached after 6 hours. Bioavailability is 25%. Weakly bound to plasma proteins. Permeability through the blood-brain barrier and placental barrier is low. It is practically not exposed to metabolism and is excreted by the kidneys unchanged. The half-life is 12 hours. In patients with heart failure, with cirrhosis, elderly patients, the absorption and clearance of lisinopril are reduced.
Impaired renal function leads to an increase in AUC (the area under the curve “plasma concentration – time”) and the half-life of lisinopril, but these changes become clinically significant only when the glomerular filtration rate is less than 30 ml / min.
Pharmacokinetics in selected groups of patients
In patients with chronic heart failure, absorption and clearance of lisinopril are reduced, bioavailability is 16%.
In patients with renal failure (creatinine clearance less than 30 ml / min), the concentration of lisinopril is several times higher than the concentration in the blood plasma of healthy volunteers, and there is an increase in the time to reach maximum plasma concentration and an increase in half-life.
In elderly patients, the concentration of lisinopril in blood plasma is increased by an average of 60% and the area under the concentration-time curve is 2 times greater than in young patients.
In patients with cirrhosis, the bioavailability of lisinopril is reduced by 30%, and clearance is reduced by 50% compared with patients with normal liver function.
Indications
– essential and renovascular hypertension (AH) (in monotherapy or in combination with other antihypertensive drugs)
– chronic heart failure (CHF) (as part of combination therapy)
– early treatment of acute myocardial infarction (combination myocardial therapy in the first 24 hours with stable hemodynamic parameters to maintain these parameters and prevent left ventricular dysfunction and heart failure)
– diabetic nephropathy (decreased albuminuria Patients with type 1 diabetes and normotensive patients with type 2 diabetes with hypertension).
Contraindications
– Hypersensitivity to lisinopril, to other ACE inhibitors and components of the
drug – a history of angioedema, including against the background of the use of ACE inhibitors
– hereditary angioedema Quincke’s edema or idiopathic edema
– pregnancy
– lactation period
– age up to 18 years (efficacy and safety have not been established)
– lactose intolerance, lactase deficiency, glucose malabsactose.
With caution
Stenosis of the aortic orifice, hypertrophic obstructive cardiomyopathy, bilateral renal artery stenosis, stenosis of a single kidney artery, condition after kidney transplantation, severe renal failure (creatinine clearance (CC) less than 30 ml / min.), primary hyperaldic hypertension, arterial hypertension inhibition of bone marrow hematopoiesis, hyponatremia (increased risk of developing arterial hypotension in patients on a low-salt or salt-free diet), hypovolemic conditions (including diarrhea, vomiting), systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), diabetes mellitus, hyperkalemia, ischemic heart disease, cerebrovascular diseases (including cerebrovascular insufficiency), severe chronic heart failure, hemodialysis using high-flow dialysis membranes (AN69 ®), advanced age.
Use during pregnancy and lactation
Use of the drug lisinopril during pregnancy is contraindicated.
When pregnancy is established, the drug should be discontinued as soon as possible. Acceptance of ACE inhibitors in the II and III trimester of pregnancy has an adverse effect on the fetus (a pronounced decrease in blood pressure, renal failure, hyperkalemia, hypoplasia of the skull bones, intrauterine death are possible). There are no data on the negative effects of the drug on the fetus if used during the first trimester. For newborns and infants, who underwent intrauterine exposure to ACE inhibitors, it is recommended to monitor for the timely detection of a pronounced decrease in blood pressure, oliguria, hyperkalemia.
During the period of treatment with the drug, breastfeeding must be canceled (there is no data on the penetration of lisinopril into breast milk).
Special instructions
A marked decrease in blood pressure most often occurs with a decrease in circulating blood volume caused by diuretic therapy, a decrease in the amount of salt in food, hemodialysis, diarrhea, or vomiting. 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 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 should be started under the strict supervision of a doctor (with caution, dose selection of the drug and diuretics). Similar rules must be followed when prescribing patients with coronary heart disease, cerebrovascular insufficiency, in which a sharp decrease in blood pressure can lead to myocardial infarction or stroke. Whenever possible, prior to the start of treatment, normalize the sodium concentration and / or replenish the volume of circulating blood, carefully monitor the effect of the initial dose of the drug on the patient. Treatment of symptomatic arterial hypotension consists of providing bed rest and, if necessary, iv fluid administration (saline infusion). Transient arterial hypotension is not a contraindication for treatment with Lisinopril, however, it may require a temporary withdrawal, or a dose reduction.
Treatment with lisinopril is contraindicated in case of cardiogenic shock and in acute myocardial infarction, if the appointment of a vasodilator can significantly worsen hemodynamics, for example, when systolic blood pressure does not exceed 100 mm RT. Art.
In patients with acute myocardial infarction, a decrease in renal function (plasma creatinine concentration of more than 177 μmol / L and / or proteinuria of more than 500 mg / 24 h) is a contraindication for the use of the drug Lisinopril. In the case of the development of renal failure during treatment with lisinopril (the concentration of creatinine in the blood plasma is more than 265 μmol / l or twice the initial level), the doctor should decide on the need to stop treatment.
With bilateral renal artery stenosis and renal artery stenosis of a single kidney, as well as with hyponatremia and / or decreased circulating blood volume or circulatory failure, arterial hypotension caused by taking Lisinopril, may lead to a decrease in renal function with the subsequent development of reversible (after discontinuation of the drug) acute renal failure. A slight temporary increase in the concentration of urea in the blood and creatinine can be observed in cases of impaired renal function, especially against the background of concurrent treatment with diuretics. In cases of a significant decrease in renal function (creatinine clearance less than 30 ml / min), caution and control of renal function are required.
Angioedema of the face, limbs, lips, tongue, epiglottis and / or larynx was rare in patients treated with ACE inhibitors, including the drug Lisinopril, can occur at any time during treatment. In this case, treatment with Lisinopril should be stopped as soon as possible and the patient should be monitored until the symptoms regress completely. In cases when there was swelling of only the face and lips, the condition most often goes away without treatment, however, it is possible to prescribe antihistamines. Angioedema with laryngeal edema can be fatal. When the tongue, epiglottis or larynx are covered, airway obstruction can occur, therefore, appropriate therapy should be immediately carried out (0.3-0.5 ml of epinephrine (adrenaline) solution 1: 1000 subcutaneously, administration of glucocorticosteroids, antihistamines) and / or measures to ensure airway patency.
Patients who have had a history of angioedema not associated with previous treatment with ACE inhibitors may have an increased risk of developing it during treatment with an ACE inhibitor.
Anaphylactic reaction was noted in patients hemodialysis using high-flow dialysis membranes (AN69 ®), which simultaneously take lisinopril. In such cases, it is necessary to consider the use of a different type of membrane for dialysis or another antihypertensive agent. Anaphylactic reactions may occur during apheresis of low density lipoproteins with dextran sulfate.
In some cases of desensitization to the hymenoptera venom (wasp, bee, etc.), treatment with ACE inhibitors was accompanied by hypersensitivity reactions. This can be avoided if you temporarily stop taking ACE inhibitors.
In patients with extensive surgery or during general anesthesia, ACE inhibitors (in particular, lisinopril) can block the formation of angiotensin II. BP reduction associated with this mechanism of action is corrected by an increase in the volume of circulating blood. Before surgery (including dentistry), it is necessary to notify the surgeon / anesthetist about the use of the drug Lisinopril.
The use of recommended doses of the drug in elderly patients may be accompanied by an increase in the concentration of lisinopril in the blood, so the selection of the dose requires special attention and is carried out depending on the patient’s kidney function and blood pressure.
At the same time, in elderly and young patients, the antihypertensive effect of the drug Lisinopril is equally pronounced.
Cough was observed with ACE inhibitors. The cough is dry, prolonged, which disappears after cessation of treatment with ACE inhibitors. With a differential diagnosis of cough, cough caused by the use of ACE inhibitors should be considered.
In some cases, hyperkalemia has been reported. Risk factors for developing hyperkalemia include kidney failure, diabetes mellitus, potassium supplements, or drugs that increase blood potassium (such as heparin), especially in patients with impaired renal function. During the period of treatment with the drug, regular monitoring of potassium, glucose, urea, and lipid ions in the blood plasma is necessary.
During the treatment period, it is not recommended to drink alcoholic beverages, since alcohol enhances the antihypertensive effect of the drug.
Caution should be exercised when performing physical exercises, in hot weather (risk of dehydration and an excessive decrease in blood pressure due to a decrease in the volume of circulating blood).
Since the potential risk of agranulocytosis cannot be ruled out, periodic monitoring of the blood picture is required.
Based on the results of epidemiological studies, it is suggested that the simultaneous administration of ACE inhibitors and insulin, as well as hypoglycemic agents for oral administration, 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 glycemic control, especially during the first month of treatment with an ACE inhibitor. ACE inhibitors can lead to the development of cholestatic jaundice with progression to fulminant necrosis of the liver, so it is necessary to stop taking the drug with increased activity of liver transaminases and the appearance of symptoms of cholestasis.
Effect of the drug on the ability to drive vehicles and mechanisms
When side effects from the central nervous system appear, it is not recommended to drive vehicles or perform work associated with an increased risk.
Composition
Each tablet contains:
Active ingredient:
lisinopril dihydrate (equivalent to lisinopril) 2.5 mg, 5 mg, 10 mg or 20 mg
Excipients:
lactose monohydrate 77.5 mg / 75.0 mg / 70 0 mg / 65 0 mg, respectively,
corn starch 49.0 mg,
povidone 6.0 mg,
talc 3.13 mg,
magnesium stearate 1.3 mg,
dyes (yellow sunset 0.02 mg in tablets containing 2, 5 mg and 5 mg of lisinopril dye azorubin 0.02 mg in tablets containing 10 mg of lisinopril titanium dioxide 0.02 mg in tablets containing 20 mg of lisinopril).
Dosage and administration
Inside, once a day in the morning, regardless of food intake, preferably at the same time.
Essential hypertension: initial dose – 10 mg / day, maintenance dose – 20 mg / day, maximum daily dose – 40 mg. Stable antihypertensive effect develops after 1-2 months, what to consider when increasing the dose. If the use of the drug in the maximum dose does not cause a sufficient therapeutic effect, then an additional prescription of another antihypertensive agent is possible.
In patients who previously received diuretics, they must be canceled 2-3 days before the start of the drug. If it is impossible to cancel diuretics, the initial dose of lisinopril should be no more than 5 mg / day.
Renovascular hypertension or other conditions with increased RAAS activity: initial dose – 2.5-5 mg / day under the control of blood pressure, renal function, serum potassium. The maintenance dose is set depending on the value of blood pressure.
In chronic renal failure (CRF), the dose is determined depending on the creatinine clearance (CC): with CC 30-70 ml / min – 5-10 mg / day, with CC – 10-30 ml / min – 2, 5-5 mg / day, less than 10 ml / min, incl. hemodialysis patients – 2.5 mg / day. The maintenance dose is determined depending on blood pressure (under the control of kidney function, potassium and sodium in the blood).
CHF (simultaneously with diuretics and / or cardiac glycosides): the initial dose is 2.5 mg / day, with a gradual increase of 2.5 mg after 3-5 days of a maintenance daily dose of 5-10 mg / day. The maximum daily dose is 20 mg. If possible, the dose of the diuretic should be reduced before starting lisinopril.
In elderly patients, a more pronounced long-term antihypertensive effect is often observed, which is associated with a decrease in the rate of lisinopril excretion (it is recommended to start treatment with 2.5 mg / day – 5 mg tablets).
Acute myocardial infarction (as part of combination therapy in the first 24 hours with stable hemodynamics): 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 is at least 6 weeks.
At the beginning of treatment or during the first 3 days after acute myocardial infarction in patients with low systolic blood pressure (120 mmHg or lower), a lower dose of 2.5 mg is prescribed. In the case of a decrease in blood pressure (systolic blood pressure below or equal to 100 mm Hg), the daily dose of 5 mg is temporarily reduced to 2.5 mg if necessary. In the case of a prolonged marked decrease in blood pressure (systolic blood pressure below 90 mm Hg for more than 1 hour), drug treatment is stopped.
Diabetic nephropathy: initial dose – 10 mg / day, which, if necessary, is increased to 20 mg / day in order to achieve diastolic blood pressure values ??below 75 mm Hg. measured in a sitting position for patients with type 1 diabetes and below 90 mm Hg in a sitting position in patients with type 2 diabetes.
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, orthostatic hypotension, tachycardia, bradycardia, onset or worsening of symptoms of heart failure, impaired atrioventricular conduction, myocardial infarction, sensation of palpitations.
From the central nervous system: emotional lability, impaired concentration, paresthesia, drowsiness, convulsive twitching of the muscles of the limbs and lips, increased fatigue, asthenic syndrome, confusion.
From the hemopoietic organs: leukopenia, neutropenia, agranulocytosis, thrombocytopenia, anemia (decreased concentration, hemoglobin, hematocrit, erythropenia).
From the respiratory system: dyspnea, dry cough, bronchospasm.
From the digestive system: dry oral mucosa, anorexia, dyspepsia, taste changes, abdominal pain, pancreatitis, jaundice (hepatocellular or cholestatic), hepatitis.
From the skin: increased sweating, alopecia, photosensitivity, pruritus.
From the genitourinary system: impaired renal function, oliguria, anuria, acute renal failure, uremia, proteinuria, decreased potency.
Allergic reactions: angioedema of the face, limbs, lips, tongue, epiglottis and / or larynx, skin rashes, urticaria, fever, positive antinuclear antibody test results, increased ESR, eosinophilia, leukocytosis, intestinal angioedema.
Other: myalgia, arthralgia / arthritis, vasculitis.
With the simultaneous use of ACE inhibitors and gold preparations (sodium aurothiomalate) intravenously, a symptom complex has been described, including facial hyperemia, nausea, vomiting, and arterial hypotension.
Laboratory indicators: hyperkalemia, hyponatremia, increased activity of hepatic transaminases, hyperbilirubinemia, hypercreatininemia, increased urea concentration.
Drug interaction
When used simultaneously with potassium-sparing diuretics (spironolactone, triamteren, amiloride), potassium preparations, salt substitutes containing potassium – the risk of hyperkalemia increases, especially in patients with impaired renal function. Therefore, they can be prescribed together only on the basis of an individual doctor s decision with regular monitoring of serum potassium and kidney function.
When used simultaneously with beta-blockers, slow calcium channel blockers, diuretics and other antihypertensive drugs, the antihypertensive effect of the drug is enhanced.
Lisinopril can be used simultaneously with beta-blockers, acetylsalicylic acid (in doses less than 300 mg / day), thrombolytics, nitrates.
With simultaneous use with vasodilators, barbiturates, phenothiazines, tricyclic antidepressants, ethanol – increased antihypertensive effect of the drug.
When used concomitantly with non-steroidal anti-inflammatory drugs (NSAIDs) (including selective cyclooxygenase-2 inhibitors), estrogens, and also adrenostimulants – reduction of the antihypertensive effect of lisinopril.
When used simultaneously with lithium preparations, it slows down the removal of lithium from the body (enhances the cardiotoxic and neurotoxic effects of lithium).
With simultaneous use with antacids and colestyramine – decreased absorption in the gastrointestinal tract.
The drug enhances the neurotoxicity of salicylates, weakens the effect of hypoglycemic agents for oral administration, norepinephrine (norepinephrine), epinephrine (adrenaline) and anti-gout drugs, enhances the effects (including side effects) of cardiac glycosides, the action of peripheral muscle relaxants, reduces the excretion of quinidine.
Reduces the effect of oral contraceptives. With the simultaneous administration of methyldopa, the risk of developing hemolysis increases.
Co-administration with selective serotonin reuptake inhibitors can lead to severe hyponatremia.
Joint use with allopurinol, procainamide, cytostatics can lead to leukopenia.
With the simultaneous use of ACE inhibitors and gold preparations (sodium aurothiomalate) intravenously, a symptom complex has been described, including facial hyperemia, nausea, vomiting, and arterial hypotension.
Overdose
Symptoms:
marked decrease in blood pressure, dry mucous membranes of the oral cavity, drowsiness, urinary retention, constipation, disturbance of water-electrolyte balance, renal failure, rapid breathing, tachycardia, palpitations, dizziness, dizziness, dizziness.
Treatment:
gastric lavage, taking activated charcoal, giving the patient a horizontal position with raised legs, replenishing the volume of circulating blood – intravenously 0, 9% solution of sodium chloride or other plasma-replacing solutions, if necessary – vasopressor drugs, monitoring the functions of the cardiovascular and respiratory systems, blood pressure, bcc, urea, creatinine, water-electrolyte balance. In the case of persistent bradycardia, the use of an artificial pacemaker.
Hemodialysis is effective.
Storage Conditions
In a dry, dark place at a temperature not exceeding 25 ° C.
Keep out of the reach and sight of children.
The Expiration of
is 3 years.
Do not use after the expiry date stated on the package.
active substance
Lisinopril
Terms leave through pharmacies
In retseptu
Dosage form
tablet
