Листрил® Plus

General characteristics. Structure:

Active agents: lisinopril of 5 mg and hydrochlorothiazide of 12,5 mg; excipients: Mannitolum, starch prezhelatinizirovanny, sodium hydroortho-phosphate, magnesium stearate, talc, starch (dry).

Description
White or almost white, round, biconvex tablets with the squeezed-out shape of heart on one party and with the dividing line on other party of a tablet.

Pharmacological properties:

Pharmacodynamics. Листрил® Plus is a combination of inhibitor of an angiotensin-converting enzyme (lisinopril) and diuretic (Hydrochlorthiazidum). 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 the general peripheric vascular resistance, the arterial pressure (AP), preloading, pressure 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 impact on fabric systems of retinas-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 hour, the maximum effect is defined in 6-7 hours, duration - 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.
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. Possesses
anti-hypertensive properties; hypotensive action develops due to expansion of arterioles. Practically does not exert impact on normal arterial pressure. The effect occurs in 1-2 hours, reaches a maximum in 4 hours and 6-12 hours proceed. Anti-hypertensive action comes in 3-4 days, but for achievement of optimum therapeutic effect 3-4 weeks can be required.
Lisinopril and Hydrochlorthiazidum if are applied at the same time, render the additive anti-hypertensive effect.

Indications to use:

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

Route of administration and doses:

To accept inside, once a day.
Arterial hypertension
The dose is established individually Recommended dose - on 1-2 tablet of 1 times a day.
Doses at a renal failure
Patients with clearance of creatinine have more than 30 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 not complicated renal failure makes 5-10 mg.
The previous therapy by diuretics
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 of Listrilom® Plus (see. Special instructions).

Features of use:

Symptomatic hypotension
Most often the expressed decrease in the ABP arises at reduction of volume of the circulating blood caused by therapy by diuretics, reduction of amount 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, 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 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.
Renal failure
At patients with a chronic renal 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 increased sensitivity / the Quincke's disease
The Quincke's disease of the person, extremities, lips, language, epiglottis and/or throat was noted seldom at the patients treated by APF inhibitors including lisinopril which can arise during any period of treatment. 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 solution of Epinephrinum (adrenaline) 1:1000 subcutaneously) 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, can be raised risk of its development during treatment by APF inhibitor (see. "Contraindications").
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.
The patients who are on dialysis:
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.

Surgery / General anesthesia
At use of means, the reducing ABP, for patients at extensive surgical intervention or during the general anesthesia, lisinopril, blocking formation of angiotensin II, can lead to the expressed decrease in the ABP which can be eliminated with increase in volume of the circulating blood.
Before surgical intervention (including stomatology) it is necessary to warn the surgeon/anaesthesiologist about use of APF inhibitors.
Potassium in serum
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).
Metabolic and endocrine effects
Thiazide diuretics can influence tolerance to glucose therefore it is necessary to adjust doses of antidiabetic medicines.
Thiazide diuretics can reduce releases of calcium with urine and 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 of Listrilom® Plus is necessary regular control in a blood plasma of potassium, glucose, urea, fats and creatinine.
During treatment it is not recommended to take alcoholic beverages as alcohol 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 volume of the circulating blood).
Influence on ability of control of vehicles and mechanisms
During treatment it is necessary to refrain from driving of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions as dizziness, especially at the beginning of a course of treatment is possible.

Side effects:

Most of patients had easy by-effects and passing. The most frequent were: dizziness, headache.
By-effects which met less often:
From cardiovascular system: the expressed lowering of arterial pressure, a stethalgia, is rare - orthostatic hypotension, tachycardia, bradycardia, emergence of symptoms of heart failure, disturbance atrioventricular
conductivity, myocardial infarction.
From a digestive tract: nausea, vomiting, abdominal pains, dryness in a mouth, diarrhea, dyspepsia, anorexia, taste change, pancreatitis, hepatitis (hepatocellular and cholestatic), jaundice.
From a nervous system: lability of mood, disturbance of concentration of attention, paresthesia, increased fatigue, drowsiness, convulsive twitchings of muscles of extremities and lips, it is rare - an asthenic syndrome, confusion of consciousness.
From respiratory system - диспноэ, a bronchospasm, an apnoea.
From integuments - a small tortoiseshell, perspiration, a hair loss, a photosensitization.
Allergic reactions: a Quincke's disease of the person, extremities, lips, language, an epiglottis and/or a throat (see. "Special instructions"), skin rashes, an itch, fever, a vasculitis, positive takes on antinuclear antibodies, increase in SOE, an eosinophilia.
From bodies of a hemopoiesis: leukopenia, thrombocytopenia, neutropenia, agranulocytosis, anemia (decrease in a hemoglobin content, hematocrit, erythrocytopenia).
From urinogenital system - uraemia, an oliguria/anury, a renal failure, an acute renal failure, decrease in a potentiality.
Laboratory indicators: a hyperpotassemia and/or a hypopotassemia, a hyponatremia, a hypomagnesiemia, a hypochloraemia, a hyperuricemia, a hyperglycemia, increase in level of urea and creatinine, it is rare - increase in activity of "hepatic" transaminases, a hyperbilirubinemia, a hypercholesterolemia, a gipertriglitseridemiya,
decrease in tolerance to glucose.
Others: dry cough, arthralgia/arthritis, mialgiya, disturbance of development of kidneys of a fruit, exacerbation of gout.

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;
with vazodilatator, barbiturates, fvnotiazina, tricyclic antidepressants, ethanol - strengthening of hypotensive action;
with non-steroidal anti-inflammatory drugs (indometacin, etc.), estrogen - decrease in anti-hypertensive effect of lisinopril;
with lithium drugs - delay of removal of lithium from an organism (strengthening of cardiotoxic and neurotoxic effect of lithium);
with antacids and kolvstiraminy - decrease in a vsavyvaniye in digestive tract.
Strengthens a neurotoxicity of salicylates, weakens action of peroral hypoglycemic means, Norepinephrinum, Epinephrinum and antigouty means, strengthens effects (including collateral) cardiac glycosides, action of peripheral muscle relaxants, reduces quinidine removal.
Reduces effect of oral contraceptives.

Contraindications:

Hypersensitivity to drug, other APF inhibitors and derivatives of streptocides, an anury, the expressed renal failure (clearance of creatinine less than 30 ml/min.), a Quincke's disease (including in the anamnesis from use
APF inhibitors), a hemodialysis with use of high-flowing membranes, a hypercalcemia, a hyponatremia, a porphyria, a prekoma, a hepatic coma, a diabetes mellitus (severe forms), pregnancy, the lactation period, age up to 18 years (efficiency and safety are not established).
With care: a bilateral stenosis of renal arteries, an aortal stenosis / a hypertrophic cardiomyopathy, a stenosis of an artery of the only kidney with the progressing azotemia, a state after transplantation of kidneys, a renal failure (clearance of creatinine less than 30 ml/min.), primary
hyper aldosteronism, arterial hypotension, marrow hypoplasia, 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 volume of the circulating blood (including diarrhea, vomiting), diseases of connecting fabric (a system lupus erythematosus, a scleroderma), a diabetes mellitus, gout, a hyperuricemia, a hyperpotassemia, coronary heart disease, cerebrovascular insufficiency, heavy chronic heart failure, a liver failure, advanced age.

Overdose:

Symptoms: the expressed decrease in the ABP.
Treatment: to cause vomiting and/or to wash out a stomach, the symptomatic therapy directed to correction of dehydration and disturbances of water-salt balance. At arterial hypotension to enter isotonic solution. Control of urea, creatinine and
electrolytes in blood serum, and also a diuresis.

Storage conditions:

To store in the dry place at a temperature not above 30 °C. To store in the place, unavailable to children. Period of validity 2 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

10 tablets in an aluminum strip. 3 strips or 10 strips are packed into a cardboard pack with the application instruction.
Sample not for sale: 4 or 10 tablets in a strip from aluminum foil. 1 strip together with the application instruction in a cardboard pack.