Lisinopril

General characteristics. Structure:

Active ingredient: 2,5 mg, 5 mg, 10 mg or 20 mg of lisinopril (in the form of a dihydrate) in 1 tablet.

Excipients: lactoses monohydrate, hydrophosphate calcium dihydrate, silicon dioxide colloid (aerosil), cellulose microcrystallic, magnesium stearate, talc.

Cardiological drug.

Pharmacological properties:

Pharmacodynamics. APF inhibitor, reduces formation of II angiotensin of angiotensin I. Decrease in content of angiotensin II leads to direct reduction of allocation of Aldosteronum. Reduces degradation of bradikinin and increases synthesis of prostaglandins. Reduces the general peripheric vascular resistance, the arterial pressure (AP), preloading, pressure in pulmonary capillaries, causes increase in minute volume of blood and increase in tolerance of a myocardium to loadings in patients with chronic heart failure. Expands arteries more than veins. Some effects are explained by influence on fabric a system renin-angiotenzinovye. At prolonged use the hypertrophy of a myocardium and walls of arteries of resistive type decreases. Improves blood supply of an ischemic myocardium.

APF inhibitors extend life expectancy at patients with chronic heart failure, slow down progressing of dysfunction of a left ventricle at the patients who had a myocardial infarction without clinical displays of heart failure. The maximum effect is defined in 6-7 hours and remains within 24 hours. At arterial hypertension the effect is noted in the first days after an initiation of treatment, stable action develops in 1-2 months. At sharp drug withdrawal did not observe the expressed increase in the arterial pressure (AP).

In addition to decrease in the ABP lisinopril reduces an albuminuria. Lisinopril does not influence concentration of glucose in blood at patients with a diabetes mellitus and does not lead to increase of cases of a hypoglycemia.

Pharmacokinetics. Absorption. After intake lisinopril is soaked up from the digestive tract (DT) on average for 25%, but absorption can vary from 6 to 60%. Bioavailability makes 25%. Meal does not influence drug absorption.

Distribution. Almost does not contact proteins of a blood plasma. The maximum concentration in a blood plasma of 90 ng/ml is reached in 7 hours. Permeability through a blood-brain and placental barrier low.

Metabolism. Lisinopril does not biotransformirutsya in an organism.

Removal. It is removed by kidneys in not changed look. The elimination half-life makes 12 hours.

Pharmacokinetics at separate groups of patients. At patients with chronic heart failure absorption and clearance of lisinopril are reduced, bioavailability makes 16%.

At patients with a renal failure concentration of lisinopril several times exceeds concentration in a blood plasma at healthy volunteers, and increase in time of achievement of the maximum concentration in a blood plasma and increase in an elimination half-life is noted.

Patients of advanced age have a concentration of drug in a blood plasma and the area under a curve "concentration time" is twice more, than at patients of young age.

Indications to use:

Route of administration and doses:

Inside, irrespective of meal, preferably at the same time.

At arterial hypertension the patient who is not receiving other antihypertensives appoint 5 mg of 1 times a day. In the absence of effect the dose is raised by each 2-3 days on 5 mg to an average therapeutic dose of 20-40 mg/days (increase in a dose usually does not lead over 40 mg/days to further decrease in the ABP). A usual daily maintenance dose - 20 mg.

The maximum daily dose - 40 mg. The full effect develops usually in 2-4 weeks from an initiation of treatment that should be considered at increase in a dose. At insufficient clinical effect the drug combination with other antihypertensives is possible.

If the patient received preliminary treatment by diuretics, then reception of such drugs needs to be stopped in 2-3 days prior to drug Lisinopril use. If it is impracticable, then the initial dose of the drug Lisinopril should not exceed 5 mg a day. In this case after reception of the first dose medical control within several hours (the maximum of action is reached approximately in 6 hours) as there can be an expressed decrease in the ABP is recommended.

At renovascular hypertensia or other states with a superactivity renin-angiotensin-aldosteronovoy of system it is reasonable to appoint also low initial dose - 2,5-5 mg a day, under the strengthened medical control (control of the ABP, function of kidneys, the maintenance of potassium ions in blood serum). A maintenance dose, continuing strict medical control, it is necessary to define depending on ABP loudspeakers.

At a renal failure in view of the fact that it lizinoprilvydelyatsya through kidneys, the initial dose has to be defined depending on clearance of creatinine. Further selection of doses should be made depending on individual reactions at regular control of function of kidneys, level of potassium, sodium in blood serum.

At clearance of creatinine of 30-70 ml/min. the initial dose makes 5-10 mg/day, at KK of 10-30 ml/min. - 2,5-5 mg/day, at KK less than 10 - 2,5 mg/day (including and the patients who are on a hemodialysis). At persistent arterial hypertension the long maintenance therapy on 10-15 mg/days is shown.

At chronic heart failure - begin with 2,5 mg of 1 times a day, with the subsequent increase in a dose by 2,5 mg in 3-5 days to the usual, supporting daily dose of 5-20 mg. The dose should not exceed 20 mg a day.

At patients of advanced age more expressed long hypotensive action is often observed that it is connected with reduction of speed of removal of lisinopril (it is recommended to begin treatment with 2,5 mg/days).

Acute myocardial infarction (as a part of a combination therapy) - in the first days - 5 mg inside, then 5 mg in a day, 10 mg in two days and then 10 mg of 1 times a day. At patients with an acute myocardial infarction to use drug not less than 6 weeks.

In an initiation of treatment or within the first 3 days after an acute myocardial infarction at patients with the low systolic ABP (120 mm hg or below) it is necessary to appoint a smaller dose - 2,5 mg. In case of decrease in the ABP (systolic the ABP is lower or 100 mm hg are equal), the daily dose in 5 mg can be lowered to 2,5 mg if necessary. In case of the long expressed decrease in the ABP (systolic the ABP is lower than 90 mm hg more than 1 hour), treatment by the drug Lisinopril should be stopped.

The diabetic nephropathy - at patients with a non-insulin-dependent diabetes mellitus is applied by 10 mg of the drug Lisinopril of 1 Times a day. It is possible to increase a dose, if necessary, to 20 mg of 1 times a day for the purpose of achievement of values of the diastolic ABP lower than 75 mm hg in situation "sitting".

At patients with an insulin-dependent diabetes mellitus dozataky, for the purpose of achievement of values of the diastolic ABP lower than 90 mm hg in situation "sitting".

Features of use:

Use at pregnancy and in the period of a lactation: Use of Lisinopril of a priberemennost is contraindicated. At pregnancy establishment administration of drug Lisinopril needs to be stopped as soon as possible. Reception of APF inhibitors in II and the III trimester of pregnancy makes an adverse effect on a fruit (the expressed decrease in the ABP, a renal failure, a hyperpotassemia, a hypoplasia of bones of a skull, pre-natal death are possible). There are no data on negative impacts of drug on a fruit in case of use during the I trimester. For newborns and babies who underwent pre-natal influence of APF inhibitors it is recommended to conduct careful observation for early detection of the expressed decrease in the ABP, an oliguria, a hyperpotassemia.

Lisinopril gets through a placenta. There are no data on release of lisinopril in breast milk. If administration of drug Lisinopril is necessary in the period of a lactation, then breastfeeding needs to be cancelled.

Symptomatic hypotension. Most often the expressed decrease in the ABP arises at decrease in the volume of the circulating blood (VCB), the caused therapy by diuretics, reduction of salt in food, dialysis, diarrhea or vomiting. At patients with chronic heart failure with a simultaneous renal failure or without it, perhaps expressed decrease in the ABP.

Under strict control of the doctor it is necessary to appoint Lisinopril the patient with coronary heart disease, cerebrovascular insufficiency at whom sharp decrease in the ABP can lead to a myocardial infarction or to a stroke. Tranzitorny arterial hypotension is not a contraindication for reception of the following dose of drug.

At drug Lisinopril use, at some patients with chronic heart failure, but with the normal or reduced ABP, decrease in the ABP can be noted that usually is not the reason for the treatment termination.

Prior to treatment by drug, whenever possible, it is necessary to normalize the content of sodium and/or to fill OTsK, to carefully control action of an initial dose of the drug Lisinopril on the patient.

At a bilateral stenosis of renal arteries and a renal artery stenosis of the only kidney, and also at a hyponatremia and/or decrease in the volume of the circulating blood (VCB) or a circulatory unefficiency the arterial hypotension caused by administration of drug Lisinopril can lead to depression of function of kidneys with the subsequent development reversible (after drug withdrawal) an acute renal failure.

At an acute myocardial infarction. Use of standard therapy is shown (trombolitik, acetylsalicylic acid, beta adrenoblockers). It is possible to use lisinopril together with intravenous administration or using therapeutic transdermal systems of nitroglycerine.

Surgical intervention / general anesthesia. At extensive surgical interventions, and also at use of other means causing decrease in the ABP, Lisinopril, blocking formation of angiotensin II, can cause the expressed not predicted decrease in the ABP.

At patients of advanced age the same dose results in higher concentration of drug in blood therefore extra care when determining a dose is required.

As it is impossible to exclude potential risk of emergence of an agranulocytosis, periodic control of a picture of blood is required. At use of drug in the conditions of dialysis with polyacryles-nitriles-membranes there can be an acute anaphylaxis therefore other type of a membrane for dialysis, or purpose of other anti-hypertensive means is recommended or.

Influence on ability of control of vehicles and mechanisms. There are no data on influence of the drug Lisinopril on ability to control of vehicles and mechanisms applied in therapeutic doses, however it is necessary to consider that developing of dizziness and drowsiness therefore it is necessary to be careful is possible.

Side effects:

Frequency of emergence of side effects is characterized as it is frequent (≥1%), is rare (<1%).

Most often: dizziness, headache, increased fatigue, dry cough, nausea, diarrhea.

From cardiovascular system: often - the expressed decrease in the ABP, orthostatic hypotension, is rare - a stethalgia, tachycardia, bradycardia, aggravation of symptoms of chronic heart failure, disturbance of atrioventricular conductivity, a myocardial infarction.

From the central nervous system: often - paresthesias, lability of mood, confusion, drowsiness, convulsive twitchings of muscles of extremities and lips, it is rare – an asthenic syndrome.

From system of a hemopoiesis: seldom - a leukopenia, a neutropenia, an agranulocytosis, thrombocytopenia, at prolonged treatment – anemia (decrease in hemoglobin, a hematocrit, an erythrocytopenia).

From respiratory system: seldom - диспноэ, a bronchospasm.

Laboratory indicators: often - a hyperpotassemia, a hyponatremia, sometimes - a hyperbilirubinemia, increase in activity of "hepatic" enzymes, a giperkreatininemiya, povysheniyekontsentration of urea and creatinine.

From the alimentary system: seldom - dryness of a mucous obolochkipolost of a mouth, dyspepsia, taste changes, anorexia, an abdominal pain, pancreatitis, hepatocellular or cholestatic jaundice, hepatitis.

From integuments: seldom - a small tortoiseshell, the increased sweating, a skin itch, an alopecia, a photosensitization.

From urinogenital system: seldom - a renal failure, an oliguria, an anury, an acute renal failure, uraemia, a proteinuria, decrease in a potentiality.

Allergic reactions: seldom - a Quincke's disease of the person, extremities, lips, language, an epiglottis and/or a throat, skin rashes, a skin itch, fever, positive takes of the test for antinuclear antibodies, increase in the blood sedimentation rate (BSR), an eosinophilia, a leukocytosis. Seldom or never – an intestinal Quincke's disease.

Others: seldom - a mialgiya, arthralgia/arthritis, a vasculitis.

Interaction with other medicines:

At simultaneous use of drug with kaliysberegayushchy diuretics (Spironolactonum, Triamterenum, amiloride), potassium drugs, the salt substitutes containing potassium, cyclosporine the risk of development of a hyperpotassemia increases, especially at an impaired renal function therefore it is possible to appoint them jointly only at regular control of maintenance of potassium ions in blood serum and function of kidneys.

The combined use of lisinopril with beta adrenoblockers, blockers of "slow" calcium channels (BMKK), diuretics, tricyclic antidepressants / neuroleptics and other antihypertensives increases expressiveness of hypotensive action.

Lisinopril slows down removal a preparatovlitiya. Therefore at combined use it is regularly necessary to control concentration of lithium in blood serum.

Antacids and Colestyraminum reduce absorption of lisinopril in digestive tract.

At combined use with insulin and hypoglycemic means for intake the risk of development of a hypoglycemia is possible.

Non-steroidal anti-inflammatory drugs (NPVP) (including the selection inhibitors of cyclooxygenase-2 (TsOG-2)), are oestrogenic, adrenostimulyator reduce hypotensive effect of lisinopril.

At simultaneous use of APF inhibitors and drugs of gold intravenously (sodium ауротиомалат) the symptom complex including a hyperemia of the person, nausea, vomiting and decrease in the ABP is described.

At combined use with selective serotonin reuptake inhibitors can lead to the expressed hyponatremia.

Combined use with Allopyrinolum, procaineamide, cytostatics can lead to a leukopenia.

Contraindications:

Hypersensitivity to lisinopril or other APF inhibitors, a Quincke's disease in the anamnesis, including from use of APF inhibitors; a hereditary Quincke's edema or an idiopathic Quincke's disease, age up to 18 years (efficiency and safety are not established).

With care: the expressed renal failures, a bilateral stenosis of renal arteries or a stenosis of an artery of the only kidney with the progressing azotemia, a state after transplantation of a kidney, an azotemia, a hyperpotassemia, a stenosis of the mouth of an aorta, a hypertrophic subaortic stenosis, primary hyper aldosteronism, arterial hypotension, cerebrovascular diseases (including insufficiency of cerebral circulation), coronary heart disease, coronary insufficiency, autoimmune general diseases of connecting fabric (including a scleroderma, a system lupus erythematosus); oppression of a marrowy hemopoiesis; a diet with sodium restriction; hypovolemic states (including as a result of diarrhea, vomiting); advanced age, a hemodialysis with use of high-flowing dialysis membranes with high-permeability (AN69®).

Overdose:

Symptoms (arise at reception of a single dose of 50 mg): the expressed decrease in the ABP, dryness of a mucous membrane of an oral cavity, drowsiness, an ischuria, a lock, concern, an acrimony.

Treatment: the specific antidote is absent. Gastric lavage, use of enterosorbents and purgatives. Intravenous administration of 0,9% of solution of sodium of chloride is shown. In case of bradycardia, steady against treatment, use of an artificial pacemaker is necessary. Control of the ABP, indicators of water and electrolytic balance is necessary. The hemodialysis is effective.

Storage conditions:

List B. In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 2 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging: