Irumed

General characteristics. Structure:

Tablets of 2,5 mg: one tablet contains
Active agent: lisinopril a dihydrate in terms of lisinopril of anhydrous 2,5 mg

Excipients: Mannitolum, phosphate calcium dihydrate, starch corn, starch corn prezhelatinizirovanny, silicon dioxide colloid, magnesium stearate.

tablets of 5 mg: one tablet contains
Active agent: lisinopril a dihydrate in terms of lisinopril of anhydrous 5 mg,

Excipients: Mannitolum, phosphate calcium dihydrate, starch corn, starch corn prezhelatinizirovanny, silicon dioxide colloid, magnesium stearate.

Tablets of 10 mg: one tablet contains
Active agent: lisinopril a dihydrate in terms of lisinopril of anhydrous 10 mg,

Excipients: Mannitolum, phosphate calcium dihydrate, starch corn, starch corn prezhelatinizirovanny, dye ferrous oxide yellow (Е 172), silicon dioxide colloid, magnesium stearate.

Tablets of 20 mg: one tablet contains
Active agent: lisinopril a dihydrate in terms of lisinopril of anhydrous 20 mg,

Excipients: Mannitolum, phosphate calcium dihydrate, starch corn, starch corn prezhelatinizirovanny, dye ferrous oxide yellow (Е 172), dye ferrous oxide red (Е 172), silicon dioxide colloid, magnesium stearate.

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 beginning of action - in 1 h. The maximum effect is defined by 6-7 h, duration of-24 h. 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 ABP. In addition to decrease in the ABP lisinopril reduces an albuminuria. At patients with a hyperglycemia contributes to normalization of function of the damaged glomerular endothelium. 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. After administration of drug inside about 25% of lisinopril are soaked up from digestive tract. Meal does not influence drug absorption. Absorption averages 30%, bioavailability - 29%. After intake the maximum concentration of lisinopril in a blood plasma is reached in 6-8 hours.
Poorly contacts proteins of a blood plasma.
Metabolism. Lisinopril does not biotransformirutsya in an organism.
Elimination half-life - 12 hours. Lisinopril poorly gets through a blood-brain barrier.

Indications to use:

Arterial hypertension (in monotherapy or in a combination with other anti-hypertensive means).
Chronic heart failure (as a part of a combination therapy for treatment of the patients accepting drugs of a foxglove and/or diuretics).
Early treatment of an acute myocardial infarction as a part of a combination therapy (in the first 24 hours with stable indicators of a hemodynamics for maintenance of these indicators and prevention of dysfunction of a left ventricle and heart failure).
Diabetic nephropathy (decrease in an albuminuria at insulin-dependent patients with the normal ABP and non-insulin-dependent patients with arterial hypertension).

Route of administration and doses:

Inside.
It is necessary to accept drug 1 time a day in the morning, to or after food, preferably at the same time.

At essential hypertensia the drug IRUMED® appoint in an initial dose 10 mg a day. The maintenance dose makes 20 mg a day. The maximum daily dose - 40 mg. For full development of effect the 2-4 weeks course of treatment drug can be required (it should be considered at increase in a dose). If use of drug in the maximum dose does not cause sufficient therapeutic effect, then perhaps additional purpose of other anti-hypertensive means.

At the patients receiving previously diuretics it is necessary to cancel them in 2 — 3 days prior to drug use. At impossibility of cancellation of diuretics the initial dose of lisinopril has to make no more than 5 mg a day.

At renovascular hypertensia or other states about the system renin-angiotensin-aljdosteronovoy raised by function the drug IRUMED® potassium concentrations in blood serum appoint in an initial dose 2,5 — 5 mg a day under control of arterial pressure, function of kidneys.

The maintenance dose is established depending on the ABP.
At patients with a renal failure and the patients who are on a hemodialysis, the initial dose is established depending on the level of the clearance of creatinine (CC). The maintenance dose is defined depending on the ABP (under control of function of kidneys, level of potassium and sodium in blood).

Clearance of creatinine (ml/min.)	Initial dose (mg a day)
30 — 70	5 — 10
10 — 30	2,5 — 5
less than 10	2,5

At chronic heart failure use of lisinopril along with diuretics and/or cardiac glycosides is possible. Whenever possible the dose of diuretic should be reduced prior to lisinopril reception. The initial dose makes 2,5 mg of 1 times a day, further it gradually (on 2,5 mg in 3-5 days) increase up to 5 — 10 mg a day. The maximum daily dose — 20 mg.

Acute myocardial infarction (as a part of a combination therapy in the first 24 hours with stable indicators of a hemodynamics)
In the first 24 hours - 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) it is possible if it is necessary, temporarily to lower a daily dose in 5 mg to 2,5 mg. 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 drug should be stopped.

Diabetic nephropathy
At patients with a non-insulin-dependent diabetes mellitus 10 mg of lisinopril of 1 times a day are applied. Lower than 75 mm hg in a sitting position are 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. At patients with an insulin-dependent diabetes mellitus the dosage same for the purpose of achievement of values of the diastolic ABP is lower than 90 mm hg in a sitting position.

Features of use:

Symptomatic hypotension
Most often the expressed decrease in the ABP arises at the decrease in volume of liquid caused by therapy by diuretics, reduction of salt in food, dialysis, diarrhea or vomiting (see INTERACTION WITH OTHER MEDICINES AND SIDE EFFECT). At patients with chronic heart failure with a simultaneous renal failure or without it development of symptomatic arterial hypotension is possible. It came to light at patients with a heavy stage of heart failure, as a result of use of high doses of diuretic, a hyponatremia or an impaired renal function more often. At such patients treatment should be begun under strict control of the doctor (with care to carry out selection of a dose of drug and diuretics). The similar rules should follow at appointment as the patient with coronary heart disease, cerebrovascular insufficiency at which sharp decrease in the ABP can lead to a myocardial infarction or a stroke. In case of development of the expressed decrease in the ABP of the patient to place in a prone position and if it is necessary, intravenously to enter 0,9% chloride sodium solution. Tranzitorny hypotensive reaction is not a contraindication for reception of the following dose of drug. At use of drug for some patients with chronic heart failure, but with the normal or reduced ABP to can/be noted decrease in the ABP that usually is not the reason for the treatment termination. If arterial hypotension passes into symptomatic, reduction of a dose of drug or the termination of treatment by drug is necessary.

At an acute myocardial infarction
Use of standard therapy is shown (trombolitik, acetylsalicylic acid, beta adrenoblockers). ИРУМЕД® it is possible to apply together with intravenous administration of nitroglycerine or using nitroglycerine transdermal systems.

Treatment by lisinopril should not begin at patients with an acute myocardial infarction who have a risk of further serious hemodynamic deterioration after use of vasodilators. These are patients with the systolic ABP of 100 mm hg or below or with cardiogenic shock. During the first 3 days after a heart attack the dose has to be reduced if systolic the ABP - 120 mm hg or below. Maintenance doses have to be reduced to 5 mg or is temporary to 2,5 mg if systolic the ABP - 100 mm hg or below. If arterial hypotension remains (systolic the ABP of less than 90 mm hg within more than 1 hour), further it is not necessary to use the drug IRUMED®.

Renal failure
At patients with chronic heart failure the expressed decrease in the ABP after an initiation of treatment with APF inhibitors can lead to further deterioration in renal function. Cases of an acute renal failure are noted.

Patients with a bilateral stenosis of renal arteries or a stenosis have arteries of the only kidney, the receiving APF inhibitors, increase in urea and creatinine in blood serum, usually reversible after the treatment termination was noted. Met at patients with a renal failure more often.

Lisinopril is not applied at an acute heart attack at patients with the expressed renal dysfunction established in change of concentration of creatinine of the serum exceeding 177 mmol/l and/or the proteinuria exceeding 500 mg/days. If renal dysfunction develops during drug use (the concentration of creatinine of serum exceeding 265 mmol/l or a doubling of value with indicators prior to treatment), the doctor has to estimate need of further use of the drug IRUMED®.

The increased sensitivity / the Quincke's disease
The Quincke's disease of the person, extremities, lips, language, epiglottis and/or throat which can arise during any period of treatment, was seldom noted at the patients treated by APF inhibitor including lisinopril. In that case treatment by drug needs to be stopped as soon as possible and for the patient to establish observation before full regression of symptoms. The state most often passes in cases when hypostasis arises only on a face and lips, without treatment, however purpose of antihistamines is possible. The Quincke's disease with hypostasis of a throat can be fatal. The paraglossa, an epiglottis or a throat can be the cause of obstruction of respiratory tracts therefore it is necessary to carry out immediately the corresponding therapy (0,3-0,5 ml 1:1000 solutions of Epinephrinum (adrenaline) subcutaneously) and/or measures for ensuring passability of respiratory tracts. It is noted that the patients of negroid race accepting APF have inhibitors, the Quincke's disease developed more often than at sick other races. At patients who in the anamnesis already had a Quincke's disease which is not connected with the previous treatment by APF inhibitors the risk of its development can be increased during treatment by APF inhibitor (see also CONTRAINDICATIONS).

Anaphylactoid reactions when performing desensitization on a gimenopter
At the patients accepting APF inhibitors during desensitization on a gimenopter, maybe, extremely seldom to appear dangerous for; lives anaphylactoid reaction. It can be avoided if temporarily to stop treatment by APF inhibitor before each desensitization.

The patients who are on a hemodialysis
Anaphylactoid reactions are noted also at the patients subjected to a hemodialysis with a high-permeability membrane (e.g. AN 69®) who at the same time accept APF inhibitors. In such cases it is necessary to consider the possibility of use of other type of a membrane for dialysis or other anti-hypertensive means.

Cough
At use of APF inhibitor cough was noted. Cough dry, long which disappears after the treatment termination by APF inhibitor. At the differential diagnosis of cough it is necessary to consider also the cough caused by APF inhibitor use.

Surgery / General anesthesia
At use of means, the reducing ABP, for patients at extensive surgical intervention or during the general anesthesia lisinopril can block formation of angiotensin II, secondary in relation to compensatory allocation of a renin. The expressed decrease in the ABP which is considered the investigation of this mechanism can be eliminated with increase in volume of the circulating blood.
Before surgical intervention (including dental surgery) it is necessary to inform the surgeon/anaesthesiologist on APF inhibitor use.

Serum potassium
The hyperpotassemia was in certain cases noted. Risk factors for development of a hyperpotassemia include a renal failure, a diabetes mellitus and simultaneous use potassium of saving diuretics (Spironolactonum, Triamterenum or amiloride), drugs of potassium or the deputies of salt containing potassium, especially at patients with an impaired renal function. If simultaneous use of lisinopril and above-mentioned means is considered necessary, they should be applied with care, regularly controlling potassium in blood serum.
At patients who have a risk of symptomatic hypotension (being on a low-salt or electrolyte-deficient diet) with or without hyponatremia, and also at patients who received high doses of diuretics the above-named states before an initiation of treatment need to be compensated (loss of liquid and salts). It is necessary to control effect of an initial dose of the drug IRUMED® on value of arterial pressure.

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

Side effects:

The most often found side effects: dizziness, headache, increased fatigue, diarrhea, dry cough, nausea.

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

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

From system of a hemopoiesis: leukopenia, neutropenia, agranulocytosis, thrombocytopenia, anemia (decrease in concentration of hemoglobin, hematocrit, erythrocytopenia).

Laboratory indicators: a hyperpotassemia, a hyponatremia, it is rare - increase in activity of "hepatic" enzymes, a hyperbilirubinemia, increase in levels of urea and creatinine.

From respiratory system: диспноэ, bronchospasm.

From a digestive tract: dryness in a mouth, anorexia, dyspepsia, taste changes, an abdominal pain, pancreatitis, hepatocellular or cholestatic jaundice, hepatitis.

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

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

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

Others: mialgiya, arthralgia/arthritis, vasculitis.

Interaction with other medicines:

At simultaneous use with kaliysberegayushchy diuretics (Spironolactonum, Triamterenum, amiloride), potassium drugs, the salt substitutes containing potassium - the risk of development of a hyperpotassemia, especially at patients with an impaired renal function increases. At simultaneous use with diuretics - the expressed decrease in the ABP. At simultaneous use with other anti-hypertensive drugs - the additive effect.

At simultaneous use with non-steroidal anti-inflammatory drugs (indometacin, etc.), estrogen, and also adrenostimulyator — decrease in hypotensive effect of lisinopril. At simultaneous use slitiy - delay of removal of lithium from an organism, with antacids and Colestyraminum - reduce absorption in digestive tract. Alcohol strengthens effect of drug.

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 idiopathic hypostasis, age up to 18 years (efficiency and safety are not established), pregnancy, the lactation period.

WITH CARE
Aortal stenosis, cerebrovascular diseases (including insufficiency of cerebral circulation), coronary heart disease, coronary insufficiency, serious autoimmune general diseases of connecting fabric (including a system lupus erythematosus, a scleroderma), oppression of a marrowy hemopoiesis, a diabetes mellitus, a hyperpotassemia, a bilateral stenosis of renal arteries, a stenosis of an artery of the only kidney, a state after transplantation of kidneys, a renal failure, an azotemia, primary aldosteronism, a hypertrophic subaortic stenosis, arterial hypotension, a diet with restriction of salt, the states which are followed by decrease in volume of the circulating blood (including diarrhea, vomiting), advanced age.

PREGNANCY AND PERIOD OF THE LACTATION
Use of lisinopril during pregnancy is contraindicated. At pregnancy establishment, treatment should be stopped as soon as possible. Reception of APF inhibitors by pregnant women in the second and third trimesters can cause death of a fruit and the newborn. 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 lowering of arterial pressure, oligurias, hyperpotassemias. At newborns the hypoplasia of bones of a skull, олигогидрамнион, deformation of bones of a skull and person, a hypoplasia of lungs, disturbance of development of kidneys of a fruit can develop.

Lisinopril gets through a placenta. There are no data on penetration of lisinopril into breast milk. For treatment by drug it is necessary to cancel breastfeeding.

Overdose:

Symptoms: the expressed decrease in the ABP, dryness in a mouth, drowsiness, an urination delay, a lock, concern, an acrimony.
Treatment: symptomatic therapy, intravenous administration of 0,9% of solution of sodium of chloride and if it is possible, use of vazopressor, control of the ABP, water and electrolytic balance. Use of a hemodialysis is possible (see. Special INSTRUCTIONS - Patients on a hemodialysis).

Storage conditions:

List B.
At a temperature not above 25 °C.
To store in the place, unavailable to children!

Issue conditions:

According to the recipe

Packaging:

Tablets of 2,5 mg, 5 mg, 10 mg, 20 mg
On 30 tablets in PVC / ПВДХ-Ал the blister. 1 blister is placed together with the application instruction in a cardboard pack.