Lisinopril

General characteristics. Structure:

Active ingredient: 5 mg, 10 mg or 20 mg of lisinopril of a dihydrate (in terms of lisinopril).

Excipients: Mannitolum, starch corn, calcium phosphate dihydrate, povidone, croscarmellose sodium, magnesium stearate.

Anti-hypertensive 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 reduces a hypertrophy of a myocardium and walls of arteries of resistive type. 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 anti-hypertensive effect develops approximately in 6 hours and remains within  24 hours. Duration of effect depends also on dose size. The beginning of action - in 1 h. The maximum effect is defined in 6-7 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 the expressed increase in the ABP is not observed. In addition to decrease in the ABP lisinopril reduces an albuminuria.

At patients with a hyperglycemia normalization and functions of the damaged glomerular endothelium promotes. 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 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%. Distribution. Almost does not contact proteins of a blood plasma. The maximum concentration in a blood plasma (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.

At patients with a renal failure concentration of lisinopril several times exceeds concentration in a blood plasma, than 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:

- 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 (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);

- a diabetic nephropathy (decrease in an albuminuria at patients with an insulin-dependent diabetes mellitus with the normal ABP and at patients with a non-insulin-dependent diabetes mellitus with arterial hypertension)

Route of administration and doses:

Inside, irrespective of meal.

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 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 lisinopril is emitted 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, the maintenance of potassium ions, sodium in blood serum. At clearance of creatinine of 30-70 ml/min. the initial dose of drug has to make 5-10 mg/day; 10-30 ml/min. - 2,5-5 mg/day; less than 10 ml/min. - 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 daily dose should not exceed 20 mg. 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 a dose of 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 1 days, 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 the expressed 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 drug 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". Patients with an insulin-dependent diabetes mellitus have the same dose, for the purpose of achievement of values of the diastolic ABP lower than 90 mm hg in situation "sitting".

Features of use:

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 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 maintenance of ions of sodium and/or to fill OTsK, to carefully control action of an initial dose of Lisinopril on the patient.
 
In case of a stenosis of renal arteries (in particular at a bilateral stenosis, or in the presence of a stenosis of an artery of the only kidney), and also at a circulatory unefficiency owing to a lack of ions of sodium and/or liquid, use of Lisinopril can lead to a renal failure, an acute renal failure which usually is irreversible after drug withdrawal.
 
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 / the 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 use of high-flowing membranes (including AN 69) the acute anaphylaxis therefore other type of a membrane for dialysis, or purpose of other anti-hypertensive means is recommended or can arise.
 
Influence on ability of control of vehicles and mechanisms. There are no data on influence of the Lisinopril on ability to control of vehicles and mechanisms applied in therapeutic doses, however it is necessary to consider that developing of dizziness therefore it is necessary to be careful is possible.

Use at pregnancy and in the period of a lactation. Use of Lisinopril at pregnancy is contraindicated. At pregnancy establishment administration of drug 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 skull hypoplasia, 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 penetration of lisinopril into breast milk. For treatment by drug it is necessary to cancel breastfeeding.

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 of consciousness, 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 concentration of hemoglobin, a hematocrit, an erythrocytopenia).

From respiratory system: seldom - an asthma, a bronchospasm. Laboratory indicators: often - a hyperpotassemia, a hyponatremia, sometimes - a hyperbilirubinemia, increase in activity of "hepatic" enzymes, a giperkreatininemiya, increase in concentration of urea and creatinine in blood serum.

From the alimentary system: seldom - dryness of a mucous membrane of an oral cavity, 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, an 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 of drugs of lithium. Therefore at combined use it is regularly necessary to control the content 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 (sodium ауротиомалат) the symptom complex including a dermahemia 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 idiopathic hypostasis, 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.

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 urination delay, 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. 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. In the place, unavailable to children, the Period of validity 2 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets of 5 mg, 10 mg, 20 mg. On 10 tablets in a blister strip packaging. 2,3 blister strip packagings together with the application instruction place in a pack from a cardboard.