Lisinopril

General characteristics. Structure:

Active ingredient: 5 mg or 10 mg of lisinopril in the form of a dihydrate.

Excipients: lactoses monohydrate (sugar milk), cellulose microcrystallic, starch prezhelatinizirovanny (starch 1500), silicon dioxide colloid (aerosil), talc, magnesium stearate.

Cure for normalization of states for cardiovascular diseases. Drug is known more than 30 years, and its efficiency is proved. In comparison with other drugs of the same group, lisinopril does not contain the organic compounds leading to a number of side effects as, for example, emergence of protein in urine. Lisinopril does not influence sugar level in blood, does not influence a liver, being removed by kidneys in not changed look. Drug is not bad transferred by patients.

For patients with chronic heart failure lazinoprit is the means allowing to prolong life.

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 anti-hypertensive effect begins 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 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. 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 at 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 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 insulin-dependent patients with the normal ABP and non-insulin-dependent patients 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 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, potassium concentrations 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, then according to reaction, it is necessary to establish a maintenance dose in the conditions of frequent control of function of kidneys, level of potassium, sodium in blood serum.

Clearance of creatinine	Initial dose
ml/min.	mg/day
30-70	5-10
10-30	2,5-5
less than 10	2,5

(including also the patients subjected to treatment by 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 people 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), 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 Lisinopril 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:

Use of lisinopril during 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.

Symptomatic hypotension. Most often the expressed decrease in the ABP arises at decrease in volume of the liquid caused by therapy by diuretics, reduction of amount 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. It comes to light at patients with a heavy stage of chronic heart failure, as a result of use of high doses of diuretics, a hyponatremia or an impaired renal function more often. At such patients treatment with Lisinopril 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.

Tranzitorny hypotensive reaction is not a contraindication for reception of the following dose of drug.

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

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

In case of a renal artery stenosis (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 sodium and/or liquid, use of Lisinopril can lead also 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 apply 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 medicines 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 a polyacryle-nitrile-membrane 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 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.

Side effects:

The most often found side effects: dizziness, a headache (at 5-6% of patients), weakness, diarrhea, dry cough (3%), nausea, vomiting, orthostatic hypotension, skin rash, a stethalgia (1-3%).

Other side effects (frequency <1%):

From immune system: (0,1%) Quincke's disease (face, lips, language, throat or epiglottis, upper and lower extremities).

From cardiovascular system: the expressed decrease in the ABP, orthostatic hypotension, a renal failure, disturbances of a heart rhythm, a cardiopalmus.

From the central nervous system: increased fatigue, drowsiness, convulsive twitchings of muscles of extremities and lips.

From system of a hemopoiesis: the leukopenia, a neutropenia, an agranulocytosis, thrombocytopenia are possible, at prolonged treatment - small decrease in concentration of hemoglobin and a hematocrit, an erythrocytopenia.

Laboratory indicators: a hyperpotassemia, an azotemia, a hyperuricemia, a hyperbilirubinemia, increase in activity of "hepatic" enzymes, especially in the presence in the anamnesis of diseases of kidneys, a diabetes mellitus and renovascular hypertensia.

Seldom found side effects (less than 1%):

From cardiovascular system: heartbeat; tachycardia; myocardial infarction; a cerebrovascular stroke at patients with the increased risk of a disease, owing to the expressed decrease in the ABP.

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

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

From an urinary system: renal failure, oliguria, anury, acute renal failure, uraemia, proteinuria.

From immune system: the syndrome including acceleration of the blood sedimentation rate (BSR), an arthralgia and emergence of antinuclear antibodies.

From the central nervous system: asthenic syndrome, lability of mood, confusion of consciousness, decrease in a potentiality.

Others: mialgiya, fever, disturbance of fetation.

Interaction with other medicines:

Lisinopril reduces removal of potassium from an organism at treatment by diuretics.

Extra care at simultaneous use of drug is required with:

- kaliysberegayushchy diuretics (Spironolactonum, Triamterenum, amiloride), potassium, the deputies of table salt containing potassium (the risk of development of a hyperpotassemia increases, especially at the broken renal function) therefore it is possible to appoint them jointly only on the basis of the individual decision of the attending physician at regular control of level of potassium in blood serum and function of kidneys.

Carefully it can be applied together:

- with diuretics: at additional administration of diuretic to the patient accepting Lisinopril, as a rule, the additive anti-hypertensive effect - risk of the expressed decrease in the ABP occurs;

1. with other anti-hypertensive means (the additive effect);
2. with non-steroidal anti-inflammatory drugs (indometacin, etc.), estrogen, and also adrenostimulyator - decrease in anti-hypertensive effect of lisinopril;
3. with lithium (release of lithium can decrease therefore it is regularly necessary to control concentration of lithium in blood serum);
4. 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, 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, a renal failure, an azotemia, a hyperpotassemia, a stenosis of the mouth of an aorta, a hypertrophic obstructive kardiomipatiya, 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 and above): 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 liquid, controlling ABP, water and electrolytic balance and normalization of the last.

Lisinopril can be removed from an organism by means of a hemodialysis.

Storage conditions:

In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity 3 years. Not to use after the date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets on 5, 10 or 20 mg. On 10 tablets in a blister strip packaging. 1, 2, 3, 4 or 5 blister strip packagings together with the application instruction place in a pack from a cardboard.