Lizoretik

General characteristics. Structure:

Active agents: lisinopril of 10 mg; hydrochlorothiazide of 12.5 mg

Excipients: calcium hydrophosphate, a mannitol, starch corn, starch prezhelatinizirovanny, dye ferrous oxide red, dye ferrous oxide yellow, magnesium stearate, the water purified.

Active agents: lisinopril of 20 mg; hydrochlorothiazide of 12.5 mg

Excipients: calcium hydrophosphate, a mannitol, starch corn, starch prezhelatinizirovanny, magnesium stearate, the water purified.

Pharmacological properties:

The combined anti-hypertensive drug containing APF inhibitor (lisinopril) and diuretic (hydrochlorothiazide). Possesses anti-hypertensive and diuretic action.
Lisinopril - APF inhibitor, reduces formation of II angiotensin of angiotensin I. Decrease leads the content of angiotensin II to direct reduction of allocation of Aldosteronum. Reduces degradation of bradikinin and increases prostaglandin synthesis. Reduces OPSS, the ABP, preloading, pressure in pulmonary capillaries, causes increase in minute volume of blood and increase in tolerance to loadings in patients with 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 - 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.

Hydrochlorothiazide - thiazide diuretic which diuretic effect is connected with disturbance of a reabsorption of ions of sodium, chlorine, potassium, magnesium, water in distal department of nephron; removal of calcium ions, uric acid detains. Has anti-hypertensive properties; hypotensive action develops due to expansion of arterioles. Practically does not exert impact on normal to the ABP. The diuretic effect occurs in 1-2 h, reaches a maximum in 4 h and proceeds 6-12 h. Anti-hypertensive action comes in 3-4 days, but for achievement of optimum therapeutic effect 3-4 weeks can be required.
Lisinopril and hydrochlorothiazide if are applied at the same time, render the additive anti-hypertensive effect.

Pharmacokinetics. Data on drug pharmacokinetics Lizoretik are not provided.

Indications to use:

— arterial hypertension (at patients to whom the combination therapy is shown).

Route of administration and doses:

Appoint inside, 1 times/days.

At arterial hypertension appoint 1 tablet (10 mg +12.5 mg) of 1 times/days. If necessary the dose can be increased before reception of 1 tablet (20 mg +12.5 mg) of 1 times/days.
Patients with KK have more than 30 ml/min. and less than 80 ml/min. drug can be used only after titration of a dose of separate components of drug. The recommended initial dose of lisinopril at an uncomplicated renal failure makes 5-10 mg.
Symptomatic hypotension can arise after reception of an initial dose of drug. Such cases meet more often at patients who had a loss of liquid and electrolytes owing to the previous treatment by diuretics. Therefore it is necessary to stop reception of diuretics in 2-3 days prior to treatment by Lizoretik.

Features of use:

Most often the expressed decrease in the ABP arises at decrease in OTsK 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, development of symptomatic hypotension is possible. It comes to light at patients with severe forms of 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 should be begun under strict control of the doctor. The similar rules should follow at appointment as the patient with an ischemic 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 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.

The Quincke's disease of the person, extremities, lips, language, epiglottis and/or throat (can arise during any period of treatment) was noted seldom at the patients treated by APF inhibitors including lisinopril. In that case treatment by lisinopril needs to be stopped as soon as possible and for the patient to establish observation before full regression of symptoms. The state most often undergoes in cases when hypostasis arose only on a face and lips, without treatment, however, perhaps purpose of antihistaminic drugs. The Quincke's disease with hypostasis of a throat can be fatal. When are captured language, the epiglottis or a throat can occur obstruction of respiratory tracts therefore it is necessary to carry out immediately the corresponding therapy (0.3-0.5 ml Epinephrinum/adrenaline solution / 1:1000 п / to) and/or measures for ensuring passability of respiratory tracts.

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.

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.

Anaphylactic reaction is noted also at the patients subjected to a hemodialysis with use of dialysis membranes with high-permeability which 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.

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.

The expressed decrease in the ABP which is considered the investigation of this mechanism can be eliminated with increase in OTsK.

Before surgical intervention (including stomatology) it is necessary to warn the surgeon/anaesthesiologist about use of APF inhibitors.

The hyperpotassemia was in certain cases noted.

Risk factors for development of a hyperpotassemia include a renal failure, a diabetes mellitus, administration of drugs of potassium or the drugs causing increase in potassium concentration in blood (for example, heparin), especially at patients with disturbance with function of kidneys. 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).

Thiazide diuretics are capable to influence tolerance to glucose therefore it is necessary to adjust doses of antidiabetic medicines.

Thiazide diuretics are capable to reduce removal of calcium with urine and to cause a hypercalcemia. The expressed hypercalcemia can be a symptom of the hidden hyperparathyreosis, it is recommended to stop treatment by thiazide diuretics before test according to function of epithelial bodies.

During treatment by drug Lizoretik is necessary regular control in a blood plasma of potassium, glucose, urea, fats and creatinine.

During treatment it is not recommended to take alcohol since ethanol strengthens hypotensive effect of drug.

It is necessary to be careful when performing physical exercises, hot weather (risk of development of dehydration and excessive decrease in the ABP because of decrease in OTsK).

Influence on ability to driving of motor transport and to control of mechanisms
During treatment patients have to abstain from driving of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions since dizziness, especially at the beginning of a course of treatment is possible.

Side effects:

Most of patients had easy side reactions and passing.
Most often: dizziness, headache.
Side reactions which met less often are listed below.
From cardiovascular system: the expressed decrease in the ABP, a stethalgia; seldom - orthostatic hypotension, tachycardia, bradycardia, emergence of symptoms of heart failure, AV conductivity disturbance, a myocardial infarction.
From the alimentary system: nausea, vomiting, abdominal pains, dryness in a mouth, diarrhea, dyspepsia, anorexia, taste change, pancreatitis, hepatitis (hepatocellular and cholestatic), jaundice; seldom - increase in activity of hepatic transaminases, a hyperbilirubinemia.
From a nervous system: lability of mood, disturbance of concentration of attention, paresthesia, increased fatigue, drowsiness, convulsive twitchings of muscles of extremities and lips; seldom - an asthenic syndrome, confusion of consciousness.
From respiratory system: диспноэ, bronchospasm, apnoea, dry cough.
Dermatological reactions: small tortoiseshell, perspiration, hair loss, photosensitization.
Allergic reactions: a Quincke's disease of the person, extremities, lips, language, an epiglottis and/or a throat, skin rashes, an itch, fever, a vasculitis, positive takes on antinuclear antibodies, increase in SOE, an eosinophilia.
From system of a hemopoiesis: leukopenia, thrombocytopenia, neutropenia, agranulocytosis, anemia (decrease in a hemoglobin content, hematocrit, erythrocytopenia).
From an urinary system: uraemia, oliguria/anury, renal failure, acute renal failure, increase in level of urea and creatinine.
From a reproductive system: decrease in a potentiality.
From a musculoskeletal system: arthralgia/arthritis, mialgiya.
From a metabolism: hyperpotassemia and/or hypopotassemia, hyponatremia, hypomagnesiemia, hypochloraemia, hyperuricemia, hyperglycemia, exacerbation of gout; seldom - a hypercholesterolemia, a gipertriglitseridemiya, decrease in tolerance to glucose.
Others: disturbance of development of kidneys of a fruit.

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 vazodilatator, barbiturates, fenotiazina, tricyclic antidepressants, ethanol hypotensive action amplifies.

At simultaneous use with NPVS (indometacin and others), estrogen anti-hypertensive effect of lisinopril decreases.

At simultaneous use with drugs of lithium delay of removal of lithium from an organism (strengthening of cardiotoxic and neurotoxic effect of lithium) is noted.
At simultaneous use with antacids and kolestraminy absorption from a GIT decreases.
Drug strengthens a neurotoxicity of salicylates.
Drug reduces action of peroral hypoglycemic means, Norepinephrinum, Epinephrinum and antigouty means.
Drug strengthens effects (including collateral) cardiac glycosides, action of peripheral muscle relaxants.
Drug reduces quinidine removal.
Reduces efficiency of oral contraceptives.

Contraindications:

— anury;
— the expressed renal failure (KK less than 30 ml/min.);
— a Quincke's disease (including in the anamnesis from use of APF inhibitors);
— a hemodialysis with use of high-flowing membranes;
— hypercalcemia;
— hyponatremia;
— porphyria;
— prekoma, hepatic coma;
— diabetes mellitus (severe forms);
— pregnancy;
— lactation period;
— age up to 18 years (efficiency and safety are not established);
— hypersensitivity to drug components;
— hypersensitivity to other APF inhibitors and derivatives of streptocides.

With care: an aortal stenosis / a hypertrophic cardiomyopathy, a bilateral stenosis of renal arteries, a stenosis of an artery of the only kidney with the progressing azotemia, a state after transplantation of kidneys, a renal failure (KK more than 30 ml/min.), primary hyper aldosteronism, arterial hypotension, a marrow hypoplasia, a hyponatremia (the increased risk of development of arterial hypotension in the patients who are on a low-salt or electrolyte-deficient diet), the states which are followed by decrease in OTsK (including diarrhea, vomiting), diseases of connecting fabric (a system lupus erythematosus, a scleroderma), a diabetes mellitus, gout, a hyperuricemia, a hyperpotassemia, an ischemic heart disease, cerebrovascular insufficiency, heavy chronic heart failure, a liver failure, advanced age.

Use of drug LIZORETIK at pregnancy and feeding by a breast
Use of drug at pregnancy and in the period of a lactation (breastfeeding) is contraindicated.

Use at abnormal liver functions
With care: liver failure.

Use at renal failures
At patients with KK> 30 ml/min. and <80 ml/min. it is possible to use drug only after titration of a dose of separate components of drug. The recommended initial dose of lisinopril at an uncomplicated renal failure makes 5-10 mg.
Use at the anury expressed to a renal failure is contraindicated (KK less than 30 ml/min.).

Use for elderly patients
With care: advanced age.

Use for children
Contraindication: age up to 18 years (efficiency and safety are not established).

Overdose:

Symptoms: the expressed decrease in the ABP.

Treatment: artificial vomiting and/or a gastric lavage, performing the symptomatic therapy directed to correction of dehydration and disturbances of water-salt balance. At arterial hypotension it is necessary to enter isotonic solution. Control of urea, creatinine and electrolytes in blood serum, and also a diuresis is necessary.

Storage conditions:

List B. Drug should be stored in the unavailable to children, dry, protected from light place, at a temperature below 25 °C.

Issue conditions:

According to the recipe

Packaging:

Tablets of 10 mg +12.5 mg: 10, 14, 20, 28, 30 or 42 pieces.

Tablets of 20 mg +12.5 mg: 10, 14, 20, 28, 30 or 42 pieces.