Diroton

General characteristics. Structure:

Active agent:
1 tablet contains:
2,5 mg of lisinopril (in the form of 2,72 mg of lisinopril of a dihydrate)
5 mg of lisinopril (in the form of 5,44 mg of lisinopril of a dihydrate)
10 mg of lisinopril (in the form of 10,89 mg of lisinopril of a dihydrate)
20 mg of lisinopril (in the form of 21,77 mg of lisinopril of a dihydrate)

Excipients: magnesium stearate, talc, Mannitolum. starch corn, hydrophosphate calcium dihydrate.

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 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 expressiveness of a 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 hypotensive action - in 1 h. The maximum effect is observed in 6-7 h. Hypotensive action remains during 24 h. Effect duration also depends on dose size.
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 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 in risk of development of a hypoglycemia.

Pharmacokinetics. After lisinopril reception inside the maximum concentration in blood serum is reached in 7 h. Poorly contacts proteins of a blood plasma. Permeability through a blood-brain and placental barrier low. Average extent of absorption of lisinopril makes about 25%, at considerable interindividual variability (6 - 60%). Food does not influence lisinopril absorption. Lisinopril is not exposed to metabolism and is removed in not changed look only by kidneys. After multiple dose the effective elimination half-life of lisinopril makes 12 h.
At patients with chronic heart failure absorption and clearance of lisinopril are reduced.
The renal failure leads to increase in AUC (the area under a curve "concentration in plasma - time") and a lisinopril elimination half-life, but these changes become clinically significant only when the glomerular filtration rate decreases lower than 30 ml/min.
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.
Lisinopril is removed from an organism by a hemodialysis.

Indications to use:

- Essential and renovascular arterial hypertension (in monotherapy or in a combination with other antigipertenziviy means).
- Chronic heart failure (as a part of a combination therapy).
- At an acute myocardial infarction with stable indicators of a hemodynamics in the first 24 h as a part of a combination therapy for 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, 1 time a day, irrespective of meal, preferably at the same time.
Essential hypertensia
The recommended initial dose for the patients who are not accepting anti-hypertensive means, 1 tablet on 10 mg a day. The usual maintenance dose makes 1 tablet on 20 mg a day; in a zavisismost from the ABP indicators it is possible to increase a dose to 40 mg/days. Maximum daily dose of 40 mg/days. At increase in a dose it is necessary to consider that full manifestation of hypotensive effect requires 2-4 weeks. If the therapeutic effect is insufficient, it is necessary to add therapy with other anti-hypertensive means.

The patients accepting diuretic means in 2-3 days prior to therapy with the drug Diroton® should stop reception of diuretic means. In cases when it is impossible, the initial dose of the drug Diroton® should not exceed 5 mg/day, at the same time it is recommended to provide medical observation of the patient after reception of the first dose since development of symptomatic arterial hypotension is possible (the maximum action is shown in 6 h after administration of drug).

The renovascular hypertensia and other states connected with a superactivity system renin-angiotensin-aldosteronovoy. The recommended initial dose makes 2,5-5 mg / суткн under the strengthened medical control (control of the ABP, function of kidneys, content of potassium in blood serum). A maintenance dose, continuing strict medical control, it is necessary to define depending on ABP loudspeakers.

Renal failure
As removal of lisinopril is carried out through kidneys, the initial dose of the drug Diroton® depends on KK indicators: at KK of 30-70 ml/min. - 5-10 mg/days, at KK of 10-30 ml/min. - 2.5-5 mg/days, less than 10 ml/min. including patients who are on a hemodialysis - 2,5 mg/days. The maintenance dose depends on clinical effect and is selected at regular measurement of indicators of function of kidneys, potassium concentration and sodium in blood.

Chronic heart failure
Initial daily dose of the drug Diroton®, equal 2,5 mg, it is possible to increase gradually in 3-5 days to the usual, supporting daily dose 5-20 mg. The dose should not exceed the maximum daily dose of 20 mg. At simultaneous use with diuretics previously, whenever possible, the dose of diuretic should be lowered.
Before to start treatment by the drug Diroton® and later, during treatment it is regularly necessary to control the arterial pressure, function of kidneys, content of potassium and sodium in blood in order to avoid development of arterial hypotension and the related renal failure.

Diabetic nephropathy
The daily dose at patients with a non-insulin-dependent diabetes mellitus with normal arterial pressure makes 10 mg in one step. In case of need the dose can be increased to 20 mg of 1 times a day for decrease in diastolic arterial pressure to 75 mm of mercury., measured in a sitting position.
Selection of a dose for the patients with an insulin-dependent diabetes mellitus having arterial hypertension is carried out according to the above-stated scheme, however optimum diastolic lower than 90 mm hg have to be the ABP.

Acute myocardial infarction
In case of use of the drug Diroton® in the first days after a myocardial infarction, the initial dose of drug makes 5 mg, to second day repeatedly appoint 5 mg, to third day - 10 mg, further the maintenance dose makes 10 mg a day. At patients with an acute myocardial infarction to use drug not less than 6 weeks.
With a low systolic arterial pressure (less than 120 mm hg) treatment is begun with a low dose (2,5 mg/days). In case of development of arterial hypotension when systolic arterial pressure less than 100 mm hg, a maintenance dose is reduced to 5 mg/days, in case of need it is temporarily possible to appoint 2,5 mg/days.
In case of the long expressed decrease in the ABP (systolic the ABP is lower than 90 mm hg more than 1 h) it is necessary to stop treatment by drug.

Features of use:

The expressed decrease in the ABP most often arises at the decrease in volume of the circulating blood 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 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 arterial hypotension is not a contraindication for reception of the following dose of drug. Prior to treatment, whenever possible, it is necessary to normalize concentration of sodium and/or to fill the volume of the circulating blood, to carefully control action of an initial dose of drug on the patient. Treatment of symptomatic arterial hypotension consists of providing a bed rest and, in case of need, in/in administrations of liquid (infusion of normal saline solution). Passing arterial hypotension is not a contraindication for treatment by the drug Diroton®, however, its temporary cancellation, or a dose decline can be required.

Treatment by the drug Diroton® contraindicated in case of cardiogenic shock and at an acute myocardial infarction if purpose of a vazodilatator can worsen significantly hemodynamics indicators, for example, when systolic the ABP does not exceed 100 mm of mercury.
At patients with an acute myocardial infarction depression of function of kidneys (concentration of creatinine in a blood plasma more than 177 µmol/l and/or a proteinuria more than 500 mg / 24 h) is a contraindication for drug Diroton® use. In case of development of a renal failure during treatment by lisinopril (concentration of creatinine in a blood plasma more than 265 µmol/l or twice exceeds initial level), the doctor has to resolve an issue of need of the termination of treatment.

At a bilateral stenosis of renal arteries and a renal artery stenosis of the only kidney, and also at a hyponatremia and / нли decrease in volume of the circulating blood or a circulatory unefficiency the arterial hypotension caused by administration of drug of Diroton® can lead to depression of function of kidneys with the subsequent development reversible (after drug withdrawal) an acute renal failure. Small temporary increase in concentration of urea in blood and creatinine can be observed in cases of an impaired renal function, especially against the background of at the same time carried out treatment by diuretics. In cases of considerable depression of function of kidneys (clearance of creatinine less than 30 ml/min.) care and control of renal function is required.

Quincke's disease of the person, extremities, lips. language, an epiglottis and/or a throat it was noted seldom at the patients treated by APF inhibitors including the drug Diroton® which can arise during any period of treatment. In that case treatment by the drug Diroton® 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 there was hypostasis only of the person and lips, without treatment, however, perhaps purpose of antihistamines. 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 of solution of Epinephrinum (adrenaline) 1:1000 subcutaneously, introduction of glucocorticosteroids. antihistaminic drugs) 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 (also see the section "Contraindications").
Anaphylactic reaction is noted also at the patients who are on a hemodialysis with use of high-flowing dialysis membranes (AN69®) which at the same time accept Diroton®. In such cases it is necessary to consider the possibility of use of other type of a membrane for dialysis or other antigipertenziviy means.
In some cases desensitizations against allergens of arthropods treatment by APF inhibitors was followed by hypersensitivity reactions. Similar can be avoided if it is previously temporary to interrupt reception of APF inhibitors.

At patients at extensive surgical intervention or during the general anesthesia APF inhibitors (in particular, lisinopril) can block formation of angiotensin II. Decrease in the ABP. associated with this mechanism of action, it is adjusted by increase in volume of the circulating blood. Before surgical intervention (including stomatology) it is necessary to warn the anesthesiologist about drug Diroton® use.

Use of the recommended drug doses by patients of advanced age can be followed by increase in concentration of lisinopril in blood therefore selection of a dose requires special attention and is carried out depending on function of kidneys and the patient's ABP.
At the same time. at elderly and young patients the anti-hypertensive effect of the drug Diroton® is expressed to the same extent.

At use of APF inhibitors cough was noted. Cough dry, long which disappears after the treatment termination by APF inhibitors. At the differential diagnosis of cough, it is necessary to consider also the cough caused by 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 content of potassium in blood (for example, heparin), especially at patients with an impaired renal function. During treatment by drug regular control in a blood plasma of potassium ions, glucose, urea, lipids is necessary.

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).

As it is impossible to exclude potential risk of emergence of an agranulocytosis, periodic control of a picture of blood is required.

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%).
Frequency of other side reactions less than 1%:

From cardiovascular system: the expressed decrease in the ABP, a stethalgia, is rare - orthostatic hypotension, tachycardia, bradycardia, emergence of symptoms of heart failure, disturbance of atrioventricular conductivity, a myocardial infarction.
From a digestive tract: nausea, vomiting, abdominal pains, dryness in a mouth, diarrhea, dyspepsia, anorexia, taste disturbance, pancreatitis, hepatitis (hepatocellular and cholestatic), jaundice (hepatocellular or cholestatic).

From integuments: a small tortoiseshell, the increased sweating, a photosensitization, a skin itch, a hair loss.
From the central 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, dry cough, bronchospasm, apnoea.

From system of a hemopoiesis: leukopenia, thrombocytopenia, neutropenia, agranulocytosis, anemia (decrease in concentration of hemoglobin, hematocrit, erythrocytopenia).
Allergic reactions: Quincke's disease of the person, extremities, lips, language, epiglottis and/or throat, intestinal Quincke's disease, vasculitis, positive reactions to antinuclear antibodies, increase in SOE, eosinophilia.
Seldom or never - an intersticial Quincke's disease (hypostasis of intersticial tissue of lungs without a transudate exit in a gleam of alveoluses).

From urinogenital system: uraemia, oliguria, anury, renal failure, acute renal failure, decrease in a potentiality.
Laboratory indicators: hyperpotassemia and/or hypopotassemia, hyponatremia, hypomagnesiemia, hypochloraemia, hypercalcemia. a hyperuricemia, increase in concentration of urea and creatinine in a blood plasma, a hyperbilirubinemia, a hypercholesterolemia, a gipertriglitseridemiya, decrease in tolerance to glucose, increase in activity of "hepatic" transaminases, at prolonged treatment perhaps small decrease in hemoglobin and a hematocrit, in some cases an agranulocytosis.
Others: arthralgia, arthritis, mialgiya, fever, 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 a giprekaliyemiya, especially at patients with an impaired renal function increases. Therefore it is possible to appoint them jointly only on the basis of the individual decision of the doctor at regular control of content of potassium in blood serum and function of kidneys.
At simultaneous use with beta adrenoblockers, blockers of "slow" calcium channels, diuretics and other antihypertensives strengthening of hypotensive effect of drug is observed.

At simultaneous use of APF inhibitors and drugs of gold (sodium ауротиомалат) intravenously, the symptom complex including a hyperemia of the person, nausea, vomiting and arterial hypotension is described.
At simultaneous use with vazodilatator, barbiturates, fenotiazina, tricyclic antidepressants, ethanol - strengthening of hypotensive effect of drug.
At simultaneous use with non-steroidal anti-inflammatory drugs (NPVP) (including the selection inhibitors of cyclooxygenase-2), estrogen, and also adrenostimulyator - decrease in anti-hypertensive effect of lisinopril.
At simultaneous use with lithium drugs - delay of removal of lithium from an organism (strengthening of cardiotoxic and neurotoxic effect of lithium).
At simultaneous use with antacids and Colestyraminum - decrease in absorption in digestive tract.

Drug strengthens a neyrotoksichiost of salicylates, weakens action of hypoglycemic means for intake, Norepinephrinum, Epinephrinum and antigouty drugs, strengthens effects (including collateral) cardiac glycosides, action of peripheral muscle relaxants, reduces quinidine removal.
Reduces effect of oral contraceptives. At a concomitant use Methyldopums the risk of development of hemolysis increases.

Contraindications:

Hypersensitivity to lisinopril and other components of drug, a Quincke's disease in the anamnesis, including, the connected using APF inhibitors, idiopathic Quincke's disease, a hereditary Quincke's edema, age up to 18 years (efficiency and safety are not established).

Overdose:

Symptoms: the expressed decrease in the ABP, dryness in a mouth, drowsiness, an urination delay, a lock, concern, an acrimony.
Treatment: a gastric lavage, reception of absorbent carbon, giving to the patient of horizontal position with the raised legs, completion of the volume of the circulating blood (VCB) - intravenous administration of plasma substituting solutions, symptomatic therapy, control of functions of cardiovascular and respiratory systems, OTsK, urea, creatinine and electrolytes in blood serum, and also a diuresis. Lisinopril can be removed from an organism by means of a hemodialysis.

Storage conditions:

List B. To store at a temperature of 15-30 °C. To store in the place, unavailable to children!

Issue conditions:

According to the recipe

Packaging:

Tablets, 2,5 mg.
On 14 tablets in the AL/PVH blister. 1 or 2 blisters with the application instruction in a cardboard pack.
Tablets, 5 mg, 10 mg and 20 mg.
On 14 tablets in the AL/PVH blister. 1, 2 or 4 blisters with the application instruction in a cardboard pack.