Lizoretik 20mg # 28 tablets

Lisoretic instruction manual

Composition

active ingredients: lisinopril, hydrochlorothiazide;

1 tablet (Lizoretik-10) contains lisinopril dihydrate in terms of lisinopril 10 mg and hydrochlorothiazide 12.5 mg

1 tablet (Lizoretik-20) contains lisinopril dihydrate in terms of lisinopril 20 mg and hydrochlorothiazide 12.5 mg

auxiliary substances: calcium hydrophosphate, mannitol (E 421), corn starch, corn starch, magnesium stearate, iron oxide red (E172) and yellow (E172) (Lizoretik-10).

Dosage form

Pills.

Basic physical and chemical properties: round biconvex tablets of light pink color, with a notch on one side. Allowed impregnations of dark color (Lizoretik - 10); white or almost white round biconvex (Lizoretik - 20).

Pharmacological group

ACE inhibitors (ACE inhibitors) and diuretics.

The ATC code is C09B A03.

Pharmacological properties

Pharmacodynamics.

Lizoretik® is a combination drug with a fixed dose of lisinopril, an ACE inhibitor (ACE) and hydrochlorothiazide, a thiazide diuretic. Both components show a complementary and additive antihypertensive effect.

Lizinopril is an inhibitor of peptidyl-dipeptidase. It suppresses ACE which catalyzes the conversion of angiotensin I into a vasoconstrictor peptide - angiotensin II. Angiotensin II also stimulates the secretion of aldosterone in the adrenal cortex.The suppression of ACE leads to a decrease in the concentration of angiotensin II, which leads to a decrease in vasopressor activity and a decrease in the secretion of aldosterone. A further decrease may lead to an increase in serum potassium levels.

Despite the fact that the mechanism by which lisinopril reduces blood pressure is considered primary suppression of renin-angiotensin-lysinopril reduces blood pressure even in patients with low-grade hypertension. ACE is identical to kininase II, an enzyme that breaks down bradykinin. It remains to be seen whether higher levels of bradykinin, a powerful vasodilator peptide, play a role in the therapeutic effect of lisinopril.

Hydrochlorothiazide is a diuretic and an antihypertensive substance. It affects the mechanism of reabsorption of electrolytes in the distal tubular kidney and increases the excretion of sodium and chloride approximately equally.Sodium-sulfur may be accompanied by some loss of potassium and bicarbonates. The mechanism of antihypertensive action of thiazides is unknown. Thiazides usually do not affect normal blood pressure.

Pharmacokinetics.

Simultaneous reception of lisinopril and hydrochlorothiazide shows little or no effect on the bioavailability of both components. There were no clinically significant pharmacokinetic interactions between the two components when taken in one tablet.

Lysinopril.

Absorption. After taking lisinopril, the maximum concentration in the blood plasma is reached within approximately 7:00.Based on the data on urinary excretion, the average amount of absorption of lisinopril in the range of studied doses (5-80 mg) is approximately 25% of the individual variation of 6-60%. Bioavailability decreases by approximately 16% in patients with heart failure. Absorption of lisinopril does not depend on food intake.

Distribution Lizinopril probably does not bind to plasma proteins other than the circulating angiotensin-converting enzyme (ACE).

It is known that lisinopril penetrates poorly through the blood-brain barrier.

Excretion of lisinopril does not lend itself to metabolism and is excreted by the kidneys completely unchanged. With multiple applications, lisinopril has an effective half-life of accumulation of 12.6 hours. The clearance of lisinopril in healthy volunteers is approximately 50 ml / min. Reduction of serum concentration indicates a prolonged terminal phase, which is not a consequence of cumulation of the drug. This terminal phase may indicate a saturation of binding with ACE and is not proportional to the dose.

Heart failure. Patients with heart failure are more exposed to lisinopril than healthy volunteers (an increase in the area under the concentration-time curve (AUC) by an average of 125%), but based on data on the withdrawal of lisinopril in the urine, it was found that there is a decrease in approximately 16% absorption compared to healthy volunteers.

Older patients older patients have higher area values under the plasma concentration-time curve (AUC) (increased by about 60%) compared with younger volunteers.

Renal failure Kidney damage reduces the elimination of lisinopril, which is excreted by the kidneys, but this decrease becomes clinically significant only if the glomerular filtration rate is below 30 ml / min. For mild to moderate renal insufficiency (creatinine clearance> 30 mL / min to <80 mL / min), the mean AUC was only increased by 13%, while in severe renal failure (creatinine clearance> 30 mL / min to < 80 ml / min) the average AUC was increased 4.5 times.

Lizinopril can be removed from the body by dialysis. During 4:00 hemodialysis, the concentrations of lisinopril in plasma decreased by an average of 60%, the clearance for dialysis was between 40 and 55 ml / min.

Dysfunction of the liver Disturbance of liver function in patients with cirrhosis led to a decrease in the absorption of lisinopril (about 30% in the determination of urinary output), but increased its effect (approximately 50%) compared with healthy volunteers due to reduced clearance.

Hydrochlorothiazide.

Hydrochlorothiazide is rapidly absorbed from the gastrointestinal tract. In humans, about 70% of the orally taken therapeutic dose is absorbed mainly in the duodenum and upper parts of the small intestine. Eating does not affect absorption, and maximum concentration is achieved within 2-4 hours after ingestion. It is reported that the volume of distribution is from 0.8 to 3 l / kg. Hydrochlorothiazide is not metabolized, but is quickly excreted by the kidneys. At least 61% of the dose is excreted unchanged for 24 hours. The half-life period is from 8 to 12:00, and 95% of the absorbed hydrochlorothiazide is excreted by the kidneys. After taking hydrochlorothiazide diuresis begins at 2:00, the peak comes about 4:00 and lasts for 6-12 hours. Hydrochlorothiazide penetrates the placenta, but does not penetrate the blood-brain barrier.

Indications

Treatment of patients with mild or moderate arterial hypertension has a stable course against the background of therapy with individual drugs in the same dosages.

Contraindications

• Hypersensitivity to lisinopril and other ACE inhibitors, to hydrochlorothiazide and sulfonamide derivatives or other components of the drug.
• Angioedema in history, associated with the use of ACE inhibitors.
• Hereditary or idiomatic angioedema.
• Hemodynamically significant stenosis of the aortic or mitral valve or hypertrophic cardiomyopathy.
• Severe renal failure or terminal stage of the disease.
• Severe liver disease.
• Pregnant women or women planning to become pregnant (see "Use during pregnancy or lactation").
• Exacerbation of gout.
• Anuria.
• Hyperuricemia.
• Hyperaldosteronism.
• Stenosis of the renal artery (bilateral or unilateral).
• Cardiogenic shock.
• A condition with unstable hemodynamics after acute myocardial infarction.
• Use for patients on hemodialysis using high-flow membranes (eg AN 69).
• The level of creatinine in the serum is> 220 μmol / l.

Interaction with other drugs and other interactions

Diuretics. If a diuretic is added at the peak of lisinopril, an additional antihypertensive effect will be obtained.

After the first dose of Lizoretik®, symptomatic hypotension may develop, the development of this condition is more likely in patients with fluid and / or salt depletion as a result of previous diuretic therapy. Diuretic therapy should be discontinued before Lizoretik® therapy begins (see the section on "Features of Use").

Food supplements containing potassium, potassium-sparing diuretics or salt substitutes containing potassium. The excretion of potassium on the background of thiazide diuretics is usually weakened by the potassium-sparing effect of lisinopril. The use of nutritional supplements containing potassium, potassium-sparing substances or substitutes for salt containing potassium, especially in patients with impaired renal function, can lead to a significant increase in potassium in the serum. If simultaneous application of Lysoretik® and any of these substances is necessary, they should be used with caution against the background of frequent monitoring of potassium content in the serum (see Section "Features of application").

Tricyclic antidepressants / antipsychotics / anesthetics. The simultaneous use of certain anesthetics, tricyclic antidepressants or antipsychotic drugs and ACE inhibitors may lead to an additional reduction in blood pressure (see Section "Features of Use").

Drugs / antipsychotics. Against the background of taking ACE inhibitors, orthostatic hypotension may develop.

Barbiturates or drugs. There may be an increase in orthostatic hypotension.

Nonsteroidal anti-inflammatory drugs / anti-inflammatory drugs (NSAIDs). The long-term use of NSAIDs (selective inhibitors of COX-2, acetylsalicylic acid> 3 g / day and nonselective NSAIDs) can reduce the hypotensive effect of both an ACE inhibitor and a thiazide. The simultaneous use of NSAIDs and ACE inhibitors may worsen the function of the kidneys. This effect is usually unavoidable. In rare cases, acute renal failure may develop, primarily in patients with impaired renal function, as in older people, in patients in a state of dehydration.

In some patients, the use of non-steroidal anti-inflammatory drugs can reduce the diuretic, natriuretic and antihypertensive effects of diuretics.

Reported an increase in serum potassium levels caused by NSAIDs and ACE inhibitors, which can lead to impaired renal function.

Sympathomimetics. Sympathomimetics can reduce the hypotensive effect of ACE inhibitors.

Other antihypertensive drugs. The antihypertensive effect of the preparation Lizoretik can be strengthened with simultaneous prescription of other drugs, which, probably, can lead to orthostatic hypotension. Simultaneous use of glyceryl trinitrate and other nitrates or other vasodilators can further reduce blood pressure.

Acetylsalicylic acid, thrombolytics, beta-blockers, nitrates. Lizoretik® can be used concomitantly with acetylsalicylic acid (cardiac doses), thrombolytic agents, beta-blockers and / or nitrates.

Antidiabetic drugs. It is known that the simultaneous use of ACE inhibitors and antidiabetic medications ( insulin , oral hypoglycemic drugs) may lead to an increase in the hypoglycemic action with a risk of developing hypoglycemia. The possibility of developing this phenomenon is more likely during the first two weeks of combined therapy and in patients with impaired renal function.

It is possible to reduce glucose tolerance, so it may be necessary to change the dose of antidiabetic drugs.

Anti-gouty agents (probenecid, sulfinpyrazone and alopurylol). Simultaneous use of ACE inhibitors and allopurinol increases the risk of kidney damage and may lead to an increased risk of leukopenia.

It may be necessary to adjust the dose of uricosuric agents, since hydrochlorothiazide can increase the level of uric acid in the serum. It may be necessary to increase the dose of probenecid or sulfinpyrazone. With the simultaneous use of thiazides, an increase in the frequency of hypersensitivity reactions to allopurinol is possible.

Cyclosporine. Simultaneous use of ACE inhibitors and cyclosporine increases the risk of kidney damage and hyperkalemia.

Lovastatin. Simultaneous use of ACE inhibitors and lovastatin increases the risk of hyperkalemia.

Cytotoxic drugs, immunosuppressants, procainamide. Simultaneous use with ACE inhibitors may lead to an increased risk of leukopenia.

Gold. Nitrite reactions (symptoms of vasodilation, including hyperemia, nausea, dizziness and arterial hypotension, which can occur in severe form) as a result of gold injections (eg sodium aurotyomalate) are more common in patients who simultaneously take lisinopril.

Amphotericin B (parenterally), carbenoxolone, corticosteroids, corticotropin (ACTH) or stimulant laxatives.Hydrochlorothiazide can enhance the disturbance of water-electrolyte balance, especially hypokalemia.

Cardiac glycosides. There is an increased risk of an overdose of cardiac glycosides due to hypoxalemia caused by thiazides.

Cholestyramine and colestipol. They can reduce or worsen the absorption of hydrochlorothiazide, so the drug Lizoretik should be taken at least 1:00 or 4-6 hours after taking these medications.

Nondepolarizing muscle relaxants (eg, tubocurarine). Hydrochlorothiazide can enhance the effect of these drugs.

Medicinal products that cause ventricular tachycardia of the "pirouette" type. As a result of the risk of developing hyperkalemia, the simultaneous use of hydrochlorothiazide and drugs whose effects are affected by changes in potassium levels in the blood serum and which can lead to ventricular pirouette tachycardia should be conducted with caution.

It is recommended to periodically monitor potassium levels in the blood serum and ECG examination if hydrochlorothiazide is taken concomitantly with drugs whose effects are affected by changes in potassium levels in the blood serum and subsequent drugs that cause polymorphic tachycardia of the pirouette type (ventricular tachycardia), including some antiarrhythmics :

• antiarrhythmics of class Ia (quinidine, hydroquinidine, disopyramide)
• antiarrhythmic drugs of class III (amiodarone, sotalol, dofetilide, ibutilide)
• some neuroleptics (eg, thioridazine, chlorpromazine, levomepromazine, trifluoroperazine, cyamemazine, sulpiride, sultopride, amisulpiride, tiaprid, pimozide, haloperidol, droperidol)
• other medications (eg, bepridil, cisapride, difemanyl, erythromycin for intravenous administration, halofantrine, misolastine, pentamidine, terfenadine, vincamine for intravenous administration).

Sotalol. Thiazide-induced hypokalemia may increase the risk of sotalol-induced arrhythmia.

Lithium preparations. Lithium preparations should usually not be prescribed concomitantly with diuretics or ACE inhibitors. Diuretics drugs and ACE inhibitors reduce renal clearance of lithium and increase the risk of lithium intoxication. If nevertheless there is a need to prescribe this combination of drugs, the level of lithium should be carefully monitored (see Section "Application Features").

Trimethoprim. Simultaneous use of ACE inhibitors and thiazides with trimethoprim increases the risk of hyperkalemia.

Corticosteroids, ACTH. Increased loss of electrolytes, especially hypokalemia.

Pressor amines (eg epinephrine (epinephrine).) A decrease in the response to pressor amines is possible, but not enough to stop their use.

Alcohol. Alcohol can enhance the antihypertensive effect of any antihypertensive drugs.

Antacids. Decrease the bioavailability of ACE inhibitors.

Metformin. Use with caution, given the risk of lactate acidosis due to possible hydrochlorothiazide-mediated functional renal failure.

Anticholinergics (atropine, biperidene). Due to the weakening of the motility of the gastrointestinal tract and the decrease in the rate of evacuation from the stomach, the bioavailability of thiazide type diuretics increases.

Cytotoxic agents (eg, cyclophosphamide, methotrexate). Thiazides can reduce the excretion of cytotoxic drugs by the kidneys and enhance their myelosuppressive effect.

Methyldopa. Individual cases of hemolytic anemia with simultaneous use of hydrochlorothiazide and methyldopa have been reported.

Effect on the results of laboratory tests. Because of the effect on calcium metabolism, thiazides can affect the results of assessing parathyroid function.

Carbamazepine. Considering the risk of symptomatic hyponatremia, it is necessary to carry out clinical and biological monitoring.

Iodine-containing contrast media. In the case of induced dehydration diuretic increased the risk for acute renal failure, especially when high doses of iodinated contrast agents. Patients in need of rehydration prior to administration iodine preparations.

Beta-blockers and diazoxide. Concomitant use of those arid diuretics, including hydrochlorothiazide, with beta blockers may increase the risk of hyperglycemia. Thiazide diuretics including hydrochlorothiazide, may exacerbate diaksozida hyperglycemic effect.

Amantadine. Thiazides, including hydrochlorothiazide, may increase the risk of side effects of amantadine.

Application features

Hypotension and violations of water-electrolyte balance.

As well as on the background of any other antihypertensive therapy, some patients may develop hypotension.

In patients with hypertension hypertensive condition more likely to develop if there is a decrease in the volume of circulating fluid, for example during treatment with diuretics, diet with salt restriction, dialysis, diarrhea or vomiting, or if the patient has severe renin-dependent hypertension (see. Forums "The interaction with other drugs and other forms of interaction" and "side reaction"). Symptomatic hypotension is also observed in patients with heart failure with or without renal failure.

This condition is more likely to occur in patients with severe heart failure due to the use of high doses of loop diuretics, hyponatremia or functional renal impairment.

Patients with risk of symptomatic hypotension, at the beginning of treatment and during dose adjustment should be monitored carefully.

In these patients at regular intervals should be the definition of electrolytes in the blood serum.

Particular attention should be paid to the treatment of patients with coronary heart disease or tserebovaskulyarnimy disease because an excessive fall in blood pressure could result in a myocardial infarction or stroke.

With the development of arterial hypotension, the patient should be put on the back and, if necessary, start infusion of normal saline. Transient hypotensive response is not a contraindication to continue therapy. After the restoration of effective blood volume and blood pressure therapy may restore the lowered dose or use of one of the components of the drug alone.

Patients should be adequately controlled in time to identify the clinical signs of water and electrolyte balance (eg, hypovolemia, hyponatremia, gipohloremichesky alkalosis, hypomagnesemia or hypokalemia), which can develop in the case of simultaneous diarrhea or vomiting. During warmer months, in patients with edema may occur hyponatremia due to blood thinners. If possible, hypovolemia eliminate and / or reduce the volume of the interstitial fluid before treatment lisinopril and carefully check the influence of the initial dose in blood pressure. In the case of acute myocardial infarction lisinopril forbidden to use if the treatment vasodilators may degrade hemodynamic status of the patient (e.g., if the systolic blood pressure of 100 mm Hg. Art.Or below) or in case of cardiogenic shock.

Stenosis of the aortic and mitral valve / hypertrophic cardiomyopathy.

As with other therapy with ACE inhibitors, lisinopril should be used with caution in patients with obstruction of the left ventricular outflow tract. If the obstruction is hemodynamically significant, reception LizoretikÔ drug is contraindicated (see. Section "Contraindications").

Impaired renal function.

Thiazides should not be used in patients with severe renal failure, they are ineffective at the level of creatinine clearance of 30 ml / min or below (i.e., severe renal failure).

LizoretikÔne The drug may be administered to patients with mild or moderate renal impairment (creatinine clearance of> 30 ml / min to <80 ml / min) until by titration of the individual components will not be established, namely that the patient needed such doses, as in the combination tablet.

If the kidney function (creatinine clearance <80 mL / min) initial dose of lisinopril should be selected depending on the performance of creatinine clearance (see. Section "Dosage and Administration") and the clinical response to treatment. For such patients it is recommended constant monitoring of the concentration of potassium, and creatinine in the blood. Patients with heart failure hypotension occurs after initiation of therapy with ACE inhibitors, may lead to renal dysfunction. Reported acute renal failure, which in such cases is usually reversible.

Some patients with unilateral or bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, treated with ACE inhibitors, there was an increase in the concentration of urea and serum creatinine, usually reversible upon discontinuation of terapii.Veroyatnost development of this condition is higher in patients with renal insufficiency. If you also have the renovascular hypertension, there is an increased risk of severe hypotension and renal insufficiency. In these patients, treatment should be started with low doses under close medical supervision, need careful dose titration. Since treatment with diuretics may promote the development of the above situations, in the first few weeks of therapy with LizoretikÔ should monitor renal function.

In some patients with hypertension who have no history of kidney disease, while the use of lisinopril and diuretic developed, usually, poor transient increase in the concentration of urea and creatinine serum. If this occurs during therapy with the drug LizoretikÔ should stop taking combination therapy may preparata.Vozobnovlenie in reduced dosage or one of the components of the drug alone.

After a kidney transplant.

Since data on the use of lisinopril patients after kidney transplantation have, use of the drug LizoretikÔ this group of patients is not recommended.

Patients on hemodialysis.

Application LizoretikÔ drug is not indicated in patients on hemodialysis for renal failure.

Anaphylactic reactions in patients on hemodialysis.

Reported high risk of anaphylactic reactions in patients undergoing dialysis through membranes with high hydraulic permeability (eg 69 AN) with concurrent therapy with ACE inhibitors. For such patients should consider using another type of dialysis membrane or destination of another group of antihypertensive drugs.

Liver disease, hepatic failure.

Very rarely, ACE inhibitors is associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant necrosis and (sometimes) a lethal iskhodu.Mehanizm this syndrome is unclear. Patients who while taking the drug LizoretikÔ developed jaundice or there is marked increase in liver enzymes should stop taking the drug and LizoretikÔ be under appropriate supervision.

Tiazidy, including hydrochlorothiazide, should of caution in patients with impaired liver function or progressive liver disease because the drug can cause internal hepatic cholestasis, as well as minimal changes in water-electrolyte balance can trigger the development of hepatic coma (see. Section: "Contra ') .

Surgery / anesthesia.

In patients during major surgery or during anesthesia drugs, causing hypotension, lisinopril may further block the formation of angiotensin II during compensatory renin release. If the development of hypotension is considered to be a consequence of this mechanism, it can be eliminated by introducing a large amount of liquid.

Metabolic and endocrine effects.

It is known that co-administration of ACE inhibitors and antidiabetic drugs (insulin, oral hypoglycemic drugs) may lead to increased blood glucose concentration decreases the risk of hypoglycemia. This phenomenon is more likely to develop during the first weeks of combination therapy and in patients with renal failure (see. Section "interaction with other drugs and other types of interactions").

Thiazide therapy may reduce the glucose tolerance. Dose adjustment may be required antidiabetic agents including insulin. Thiazides may decrease the excretion of calcium in the urine and can cause an abrupt and a slight increase of calcium in blood serum. Severe hyperkalemia can be a sign of hidden hyperparathyroidism. Should stop taking those arid diuretics to conduct tests to assess the function of parathyroid glands. Increasing the concentration of cholesterol and triglycerides may be associated with the therapy arid those diuretics.

Thiazide therapy may accelerate occurrence giperurikemiita / or gout in some patsientov.Odnako lisinopril may increase the levels of uric acid in the urine and thereby weaken the hyperuricemic effect of hydrochlorothiazide.

Hypersensitivity / angioedema.

It reported isolated cases of angioedema person, extremities, lips, tongue, vocal cords and / or the larynx in patients treated with ACE inhibitors, including lisinopril. These phenomena may develop at any stage of treatment. In this case, you should immediately cancel the lisinopril and install the appropriate supervision to ensure the complete disappearance of symptoms before the patient is discharged. Even in those cases when there is a swelling of the tongue only without the development of respiratory failure, may require prolonged observation of the patient, since treatment with antihistamines and corticosteroids may not be sufficient.

Very rarely reported fatal cases of angioedema due to laryngeal edema or swelling tongue. When developing swelling of the tongue, glottis or larynx, are most likely to cause airway obstruction, should immediately begin the appropriate emergency treatment. It may include the appointment of adrenaline and / or support the patient's airway patency. The patient should be under medical supervision until complete and sustained resolution of symptoms. Angioedema may also affect the intestine and manifested acute abdominal pain, nausea, vomiting and diarrhea.

Patients who have had a history of angioneurotic edema place not associated with ACE inhibitors, may be at increased risk of angioedema during treatment with ACE inhibitors (cm. CATEGORY "Contra ').

Patients receiving therapy with thiazides, hypersensitivity reactions may occur regardless of the presence or absence of a history of allergy or bronchial asthma. It reported an exacerbation or activation of systemic lupus erythematosus during treatment with thiazides.

Race.

The incidence of edema anginevrotichnogo during treatment with ACE inhibitors higher in patients blacks compared with those of other races. As is the case with other ACE inhibitors, lisinopril may less effectively reduce blood pressure in patients blacks compared with those of other races, it is probably a consequence of the greater frequency of low-renin hypertension in these patients.

Anaphylactic reactions in connection with apheresis low density lipoprotein (LDL).

In rare cases, patients receiving therapy with ACE inhibitors, developing life-threatening anaphylactic reactions during apheresis low density lipoprotein (LDL) dextran sulfate. These symptoms can be avoided by temporarily discontinuing therapy with ACE inhibitors before each apheresis.

Desensitization.

Patients receiving ACE inhibitors during desensitizing therapy (eg, poison Hymenoptera), develops a continuous anaphylactic reactions. In these patients this reaction were avoided by temporarily abandoning the ACE inhibitors, but it reappeared under a random re-appointment of the drug.

Hyperkalemia.

In some patients treated with ACE inhibitors, including lisinopril, there was an increase of potassium in the blood serum. risk group for the development of hyperkalemia included patients suffering from renal failure, diabetes, and those who use the same time sparing diuretics, nutritional supplements with potassium or salt substitutes containing potassium, and those patients who are taking other medications that can cause the potassium increase in serum blood (e.g., heparin). If concomitant use of the above funds necessary to read, it is recommended regular monitoring of potassium serum.

Neutropenia / agaranulotsitoz / Thrombocytopenia / Anemia.

It reported on the development of neutropenia, agranulocytosis, thrombocytopenia, and anemia in patients treated with ACE inhibitors. In patients with normal renal function with no other complicating factors neutropenia is rare. Neutropenia and agranulocytosis resolved upon discontinuance of the ACE inhibitors.

In patients with vascular collagen who receive immunosuppressant therapy, treatment with allopurinol or procainamide, or have a combination of these complicating factors, especially against the background of an existing renal dysfunction, lisinopril should be used with extreme caution. Some of these patients developed serious infections, which in several cases did not respond to intensive antibiotic therapy. When appointing such patients, lisinopril should regularly monitor the number of white blood cells, and the patient should be advised to report the signs of infection.

Cough.

Cough development was reported in patients taking ACE inhibitors. What is characteristic, cough, permanent and stops after the abolition of therapy. The fact that ACE inhibitors cause a cough should be considered when conducting a differential diagnosis of cough.

Lithium preparations.

Combination of administration of ACE inhibitors and lithium preparations should be avoided (see Section "Interaction with Other Drugs and Other Interactions").

Pregnancy.

Do not start taking ACE inhibitors during pregnancy. While continuing therapy with ACE inhibitors is considered necessary, patients who plan a pregnancy should be transferred to alternative antihypertensive therapy, including drugs that have an established safety profile for use during pregnancy. If pregnancy occurs, treatment with ACE inhibitors should be stopped immediately and, if possible, alternative therapy should be started (see Sections "Contraindications" and "Use during pregnancy or lactation").

Photosensitivity.

During treatment, those arid diuretics reported cases of photosensitization reactions. If photosensitization occurs during treatment, it is recommended to cancel the drug. If the doctor believes that you need to re-designate the drug, it is recommended to protect areas of the body that are exposed to sunlight or artificial UV irradiation.

Laboratory indicators.

The drug may interfere with the results of the following laboratory tests: hydrochlorothiazide may reduce the level of protein-bound iodine in blood plasma (treatment with hydrochlorothiazide should be discontinued before a laboratory examination to assess parathyroid function) and increase the concentration of free bilirubin in serum.

Use during pregnancy and lactation

The drug is contraindicated to apply to pregnant women or women who plan to become pregnant. If during pregnancy, this drug is confirmed pregnancy, its use must be immediately stopped and replaced with another drug approved for use in pregnant women.

The ability to influence the reaction rate when driving vehicles or other mechanisms

Due to the development of adverse reactions, especially at the beginning of therapy, Lizoretik® may have little or no effect on the reaction rate (see Section "Adverse Reactions"), therefore, one should refrain from managing motor vehicles and / or working with other mechanisms. The risk of this increases if the drug LizoretikÔ is combined with the intake of alcohol.

Dosing and Administration

Arterial hypertension.

Adults.

A fixed-dose combination drug should not be used to initiate therapy. A fixed-dose combination drug can replace a combination of 10 mg or 20 mg of lisinopril and 12.5 mg of hydrochlorothiazide in patients whose condition has been stabilized against the background of therapy with individual active substances in the same dosages, appointed in the form of separate preparations. The usual dose is 1 tablet once a day. Like any other medications that are taken 1 time per day, Lizorethik should be taken at about the same time every day.

If the desired therapeutic effect can not be achieved within 2-4 weeks of treatment, the dose can be increased to 2 tablets once a day.

Prior therapy with diuretics.

After taking the first dose of Lizoretik®, symptomatic hypotension may develop, this development is more likely in patients with depletion of fluid and / or salt as a result of previous diuretic therapy. Therapy with diuretics should be discontinued 2-3 days before therapy with Lizoretik®. If this is not possible, then start treatment with individual components in a low dose (lisinopril in a dose of 5 mg).

Patients with renal insufficiency.

The drug Lizoretik® can not be used as an initial therapy for patients with renal insufficiency.

Patients with mild or moderate renal insufficiency (creatinine clearance> 30 and <80 ml / min) Lizoretik® can be used only after titrating the dose of individual components.

In this case, the recommended dose of lisinopril, which is prescribed as a separate drug, is 5-10 mg.

Patients of advanced age.

It is known that the efficacy and tolerability of lisinopril and hydrochlorothiazide in their simultaneous administration were similar in elderly patients and in younger patients with arterial hypertension.

In the dosage range of 20 mg to 80 mg, the efficacy of lisinopril was similar in elderly patients (aged 65 years) and in young patients with hypertension. In elderly patients with hypertension, monotherapy with lisinopril was also effective in reducing diastolic blood pressure, as was monotherapy with hydrochlorothiazide or atenolol. If the elderly patient has decreased renal function, the initial dose of lisinopril should be adjusted (see "Patients with renal insufficiency").

Children

Lizoretik is not suitable for use in children.

Safety and effectiveness of use for children and adolescents are not established.

Overdose

There is no specific information on the treatment of an overdose of lisinopril / hydrochlorothiazide.

Lysinopril.

Symptoms. The most likely symptoms of overdose are arterial hypotension, electrolyte imbalance, renal failure, circulatory shock, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety and cough.

Hydrochlorothiazide.

The most common signs and symptoms are caused by elimination of electrolytes (hypokalemia, hypochloraemia, hyponatremia) and dehydration due to excessive use of diuretics: seizures paresis; renal failure, oppression of consciousness, including to whom.

Symptoms. Tachycardia, shock, weakness, confusion, dizziness, muscle spasms, paresthesia, exhaustion, impaired consciousness, nausea, vomiting, thirst, polyuria, oliguria, anuria, hypokalemia, hyponatremia, hypochloremia, alkalosis, elevated blood urea nitrogen level kidney failure). With the simultaneous appointment of cardiac glycosides, hypokalemia can increase cardiac arrhythmia.

Treatment. Treatment is symptomatic and supportive. Therapy with Lizoretik® should be discontinued and the patient should be carefully monitored. Therapeutic measures depend on the nature and severity of the symptoms. Take measures to prevent absorption and use methods to accelerate elimination.

In case of severe arterial hypotension, the patient should be placed in a supine position with raised lower limbs and quickly begin infusion of physiological saline. It is possible to consider the possibility of treatment of angiotensin II (if it is available). Like all ACE inhibitors, lisinopril can be removed from the general blood flow by hemodialysis (see Section "Pharmacological properties"). The use of polyacrylonitrile dialysis membrane with high hydraulic permeability should be avoided. The level of electrolytes and serum creatinine should be monitored. For the treatment of resistant bradycardia is shown the installation of a pacemaker. Frequent monitoring of vital signs, serum electrolyte and serum creatinine levels should be carried out.

If these measures fail to achieve the desired result, catecholamines should be administered. Bradycardia can also be reduced by taking atropine.

Adverse Reactions

Against the background of the reception of individual components, adverse reactions were reported which could also develop with the use of Lizoretik®.

Side effects caused by lisinopril and other ACE inhibitors.

• On the part of the blood and lymphatic system: lymphadenopathy, anemia, agranulocytosis, oppression of bone marrow function, hemolytic anemia, leukopenia, thrombocytopenia, neutropenia, autoimmune diseases.
• Cardiovascular system: palpitation, tachycardia, arterial hypotension (including orthostatic hypotension), cerebral circulation disorders, Raynaud phenomenon, imbalance, myocardial infarction or stroke, possibly due to severe arterial hypotension in high-risk patients.
• Mental disorders: mood changes, sleep disturbance, confusion, disorientation.
• From the side of the nervous system: dizziness, imbalance, paresthesia, headache, taste disorder, impaired sense of smell.
• From the organs of hearing and balance: vertigo.
• On the part of the respiratory system, chest and mediastinal organs: cough *, bronchospasm, dyspnea, rhinitis, sinusitis, allergic alveolitis, eosinophilic pneumonia, upper respiratory tract infections.
• On the part of the gastrointestinal tract: diarrhea, nausea, vomiting, dry mouth, glossitis, pancreatitis, angioedema, intestinal edema, abdominal pain, digestive disorders, decreased appetite, constipation.
• On the part of the digestive system: hepatitis, hepatocellular or cholestatic jaundice, liver failure **.
• From the skin and subcutaneous tissue: rash, hypersensitivity, angioedema ***, symptom complex ****, alopecia, urticaria, pruritus, psoriasis, increased sweating, fever, hyperemia, skin disorders (pemphigus, toxic epidermal necrolysis, Stevens syndrome -Johnson, multiform erythema, pseudolymphoma of the skin)
• From the side of metabolism and nutrition: hypoglycemia.
• From the musculoskeletal system and connective tissue: muscle spasms, muscle weakness.
• From the endocrine system: inadequate secretion of ADH.
• From the side of the kidneys and urinary tract: oliguria / anuria, renal dysfunction, acute renal failure, proteinuria.
• Complications of a general nature: increased fatigue, asthenia, discomfort in the chest.
• On the part of the reproductive system and mammary glands: impotence, gynecomastia.
• Laboratory indicators *****: increased activity of liver enzymes, increased serum creatinine concentration, increased blood urea, decreased hemoglobin, reduced hematocrit, serum bilirubin. * Cough, caused by therapy with ACE inhibitors, is characterized as a permanent,

unproductive, disappears when the drug is withdrawn. This should be taken into account in the differential diagnosis of cough.

** There was very rarely a report of patients in whom unwanted development of hepatitis led to hepatic insufficiency.Patients who have developed jaundice against the background of therapy or a significant increase in hepatic enzyme activity should stop using Lizoretik® and undergo a proper medical examination.

*** Individual cases of angioedema, facial, extremities, lips, tongue, glottis and / or larynx have been reported (see "Features of Use" section).

**** The development of a symptom complex that may include one or more of the following symptoms has been reported: fever, vasculitis, myalgia, arthralgia / arthritis, positive antinuclear antibodies (ANA), increased erythrocyte sedimentation rate (ESR), eosinophilia and leukocytosis, rash, photosensitivity or other dermatological manifestations.

***** There was a slight increase in serum creatinine and urea concentration. These phenomena are usually reversible when the drug is discontinued. A slight decrease in hemoglobin and hematocrit was reported. Bone marrow suppression has been reported, manifested by anemia and / or thrombocytopenia. Hyper- or hypokalemia and hyponatremia were observed. There was reported a single increase in the activity of hepatic enzymes and / or bilirubin content, but the association with the drug containing lisinopril and hydrochlorothiazide was not established.

Individual cases of development of syncope and pain in the chest have been reported, but the association with the administration of the drug containing lisinopril and hydrochlorothiazide has not been established.

There are reports of the development of neuropathy against the background of the administration of ACE inhibitors.

Side effects due to hydrochlorothiazide.

• Infections and infestations: sialodenitis.
• On the part of the immune system: hypersensitivity reactions, including a prophylactic reaction, shock.
• On the part of the blood and lymphatic system: leukopenia, neutropenia / agranulocytosis, thrombocytopenia, aplastic anemia, hemolytic anemia, suppression of bone marrow function.
• From the side of metabolism and nutrition: anorexia; hyperglycemia; glucosuria; hyperuricemia, which can provoke gouty attacks in patients with asymptomatic course of the disease, abnormal electrolyte balance, including hyponatremia and hypokalemia; hypomagnesemia; hypercalcemia; increased blood lipid levels, gout, reduced glucose tolerance, which can lead to the manifestation of latent diabetes mellitus, hypochloraemic alkalosis, which can induce hepatic encephalopathy or hepatic coma.
• Mental disturbances: anxiety, depression, mood changes, sleep disturbance, confusion, disorientation, drowsiness, nervousness.
• From the nervous system: dizziness, headache, convulsions, paresthesia.
• On the part of the organs of vision: xantopsy, temporary visual impairment.
• From the organs of hearing and balance: vertigo.
• From the cardiovascular system: arrhythmia, orthostatic arterial hypotension.
• On the part of the respiratory system, chest and mediastinal organs: respiratory distress syndrome, including pneumonitis and pulmonary edema.
• From the gastrointestinal tract: irritation of the gastric mucosa, constipation, dry mouth, thirst, nausea, vomiting.
• On the part of the digestive system: jaundice (jaundice caused by intrahepatic cholestasis), pancreatitis, cholecystitis
• From the skin and subcutaneous tissue: vasculitis, including cutaneous, necrotizing angiitis, toxic epidermal necrolysis, Stevens-Johnson syndrome, photosensitivity, rash, eczema, dermal lupus-like reactions, reactivation of cutaneous manifestations of systemic lupus erythematosus, hives, purpura.
• From the musculoskeletal system and connective tissue: muscle spasms and pain.
• From the kidneys and urinary tract: kidney failure, kidney dysfunction and interstitial nephritis.
• From the genitals: sexual disorders.
• General complications: exhaustion.

Shelf life

3 years.

Storage conditions

Store in original packaging at a temperature not exceeding 25 ° C.
Keep out of the reach of children.

Packaging

For 14 tablets in a blister pack. 2 blisters in a cardboard box.

Category of leave

On prescription.