Instructions for use LIPRAZID

Contraindications

Absolute:

• Age up to 18 years;
• Pregnancy;
• Lactation;
• Concomitant use of lithium preparations;
• Idiopathic or hereditary angioedema or angioedema caused by the use of angiotensin-converting enzyme inhibitors (history);
• Severe renal dysfunction (creatinine clearance less than 30 ml/min), anuria, bilateral renal artery stenosis or stenosis of the artery of a single kidney, as well as the period of hemodialysis using high-strength membranes (polyacrylonitrile, methylsulfonate);
• Hypersensitivity to Liprazide components or sulfonamide derivatives.

Relative (special care should be taken due to the risk of complications):

• Mitral and/or aortic stenosis;
• Cardiac ischemia;
• Cerebrovascular disorders;
• Impaired kidney/liver function;
• Alcoholism;
• Conditions accompanied by increased potassium levels in the blood;
• The period before surgery using general anesthesia;
• Obstructive hypertrophic cardiomyopathy;
• Severe heart failure;
• Diabetes;
• Violations of water and electrolyte balance;
• Renal artery stenosis;
• Hypovolemia;
• Collagenoses;
• Elderly age;
• Low sodium diet.

Caution should be exercised when prescribing the drug to patients on hemodialysis.

Liprazid 10 tablets for high blood pressure, 30 pcs.

Non-melanoma skin cancer

An increased risk of nonmelanoma skin cancer (NMSC) with increasing cumulative dose of HCTZ was found in two pharmacoepidemiological studies. The photosensitizing effect of HCTZ may act as a possible mechanism for the development of this pathology.

Patients taking HCTZ alone or in combination with other drugs should be informed of the risk of developing NMSC, especially with long-term use, the need for regular skin checks, and to immediately report new lesions or any suspicious skin lesions, changes in skin lesions or moles.

To reduce the risk of developing skin cancer, patients should be advised of possible preventive measures, such as limiting exposure to sunlight and UV radiation, and if exposed, the need for adequate skin protection. It is necessary to examine suspicious skin lesions as soon as possible, including histological examination of biopsy material.

Patients with a previous history of NMSC may also need to review the use of HCTZ.

Symptomatic hypotension

Symptomatic hypotension is rare in patients with uncomplicated hypertension and is more likely in patients with hypovolemia, electrolyte imbalance (including hyponatremia, hypochloremic alkalosis, hypomagnesemia or hypokalemia), for example, during diuretic therapy, low-salt diet, dialysis, diarrhea , vomiting or in severe forms of renin-dependent hypertension. Such patients should undergo regular determination of serum electrolytes. In patients at increased risk of symptomatic hypotension, initiation of therapy and dose adjustment should be carried out under close medical supervision. Particular attention is necessary for patients with coronary heart disease or cerebrovascular diseases, in whom an excessive decrease in pressure can lead to myocardial infarction or stroke.

If arterial hypotension develops, the patient should be placed on his back and, if necessary, given an intravenous infusion of saline sodium chloride solution. Transient arterial hypotension when taking the drug is not a contraindication for its further use. After normalization of blood pressure and restoration of effective blood volume, it is possible to resume therapy with the drug lisinopril / hydrochlorothiazide in a reduced dosage or separately with one of the components.

In some patients with heart failure and normal or low blood pressure, lisinopril may further reduce systemic blood pressure. This effect is expected and is not usually a reason to stop treatment. If symptomatic hypotension may require dose reduction or discontinuation of the lisinopril/hydrochlorothiazide combination drug.

Dual blockade of renin-angiotensin (RAAS)

Concomitant use of ACE inhibitors (including lisinopril), angiotensin II receptor blockers (ARBs) or aliskiren increases the risk of arterial hypotension, hyperkalemia and decreased renal function (including acute renal failure). Therefore, dual blockade of the RAAS by combining ACE inhibitors with ARBs or aliskiren is not recommended.

If double blockade of the RAAS is considered absolutely necessary, this should only occur under specialist supervision and with frequent careful monitoring of renal function, blood electrolyte levels (especially potassium), and blood pressure.

ACE inhibitors and ARBs should not be used concomitantly in patients with diabetic nephropathy.

Previous diuretic therapy

Symptomatic hypotension may occur after the initial dose of the lisinopril/hydrochlorothiazide combination drug. This is more likely in patients with dehydration and/or salt deficiency as a result of previous diuretic therapy. Diuretic therapy should be discontinued 2-3 days before starting the lisinopril/hydrochlorothiazide combination. If this is not possible, treatment should be started with lisinopril 5 mg alone.

Aortic and/or mitral valve stenosis/hypertrophic cardiomyopathy

Like other ACE inhibitors, lisinopril is not recommended for use in patients with mitral valve stenosis and left ventricular outflow obstruction (for example, aortic stenosis or hypertrophic cardiomyopathy).

Renal dysfunction

Thiazides may not be acceptable diuretics for use in patients with impaired renal function. They are ineffective when CC is 30 ml/min or lower (moderate or severe renal failure).

The combination drug lisinopril/hydrochlorothiazide should not be used as initial therapy in any patient with impaired renal function.

Lisinopril/hydrochlorothiazide should not be prescribed to patients with renal impairment (creatinine clearance ≤ 80 ml/min) until the need for the exact doses contained in the combination tablet has been established by titrating the doses of the individual active substances of the drug.

In patients with heart failure, arterial hypotension that occurs after initiation of therapy with ACE inhibitors can lead to further impairment of renal function with the possible subsequent development of reversible (after discontinuation of the drug) acute renal failure.

Some patients with arterial hypertension without obvious signs of kidney disease may experience slight transient increases in serum urea and creatinine levels, especially if lisinopril is used concomitantly with diuretics. The likelihood of this happening is higher in patients with pre-existing renal impairment. This condition may require dose reduction and/or discontinuation of the diuretic and/or lisinopril.

Patients after kidney transplantation

There is no experience with the use of the drug in patients with a recently transplanted kidney, so the drug should not be used in this group of patients.

Anaphylactoid reactions during hemodialysis

The use of lisinopril/hydrochlorothiazide is not indicated in patients who require dialysis for renal failure.

Cases of anaphylactic reactions have been reported in patients undergoing hemodialysis procedures using high-flow membranes (for example AN 69) and concomitant treatment with ACE inhibitors. In such patients, it is recommended to use a different type of dialysis membrane or a different class of antihypertensive drugs.

Anaphylactoid reactions during low-density lipoprotein (LDL) apheresis

Life-threatening anaphylactic reactions have been rarely reported in patients receiving ACE inhibitors during LDL apheresis with dextran sulfate. To avoid these reactions, ACE inhibitors should be temporarily suspended before each apheresis procedure.

Liver diseases

Thiazides should be used with caution in patients with impaired liver function or progressive liver disease, since minor changes in fluid and electrolyte balance may precipitate sudden hepatic coma.

Very rarely, the use of ACE inhibitors has been associated with a syndrome that begins with cholestatic jaundice or hepatitis and progresses to fulminant hepatic necrosis, sometimes fatal. The mechanism of this syndrome is unknown. If patients taking lisinopril/hydrochlorothiazide develop jaundice or significantly increased serum liver enzymes, the drug should be discontinued and the patient should be monitored until symptoms resolve.

Surgery/general anesthesia

During major surgery or during anesthesia with drugs that cause hypotension, lisinopril can block the formation of angiotensin II due to compensatory release of renin, causing a pronounced, unexpected decrease in blood pressure. If arterial hypotension develops, which can be explained by this mechanism, it should be corrected by increasing the volume of blood volume.

Metabolic and endocrine effects

It is known that the combined use of ACE inhibitors and antidiabetic drugs (including insulin) can cause an increase in blood glucose concentrations and reduces the risk of hypoglycemia. This phenomenon is more likely to develop in the first weeks of combination therapy and in patients with impaired renal function (see Section “Interaction with other drugs and other types of interactions”). Thiazide therapy can lead to impaired glucose tolerance and the development of hyperglycemia. Therefore, dosage adjustments of antidiabetic agents, including insulin, may be necessary. In diabetic patients receiving oral antidiabetic agents or insulin, plasma glucose levels should be carefully monitored during the first month of treatment with an ACE inhibitor. Manifestation of latent diabetes mellitus is possible during thiazide therapy.

Thiazide diuretic therapy may be associated with increased levels of cholesterol, free bilirubin (due to displacement from albumin) and triglycerides in the blood plasma.

Thiazides can reduce plasma levels of protein-bound iodine without evidence of thyroid dysfunction.

In some patients, the use of thiazide diuretics may provoke hyperuricemia and/or worsen the course of/provoke an attack of gout in predisposed patients. However, lisinopril may increase the excretion of uric acid and thus may reduce the hyperuricemic effect of hydrochlorothiazide.

Electrolyte imbalance

All patients receiving diuretic therapy should have serum electrolyte levels measured periodically to identify possible fluid and electrolyte imbalances.

Thiazides, including hydrochlorothiazide, can cause water and electrolyte imbalance, incl. hypovolemia, hyponatremia, hypokalemia, hypomagnesemia, hypochloremic alkalosis. Determination of serum and urine electrolyte levels is especially important when the patient is experiencing excessive vomiting and/or diarrhea or is receiving parenteral fluids. Warning symptoms of fluid and electrolyte imbalance, regardless of the cause, are dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, confusion, cramps, muscle pain or cramps (Crump), muscle fatigue, hypotension, oliguria, tachycardia, nausea , vomit.

The drug should be prescribed with caution to patients who are on a salt-free diet.

In patients with edema in hot weather, dilutional hyponatremia may occur. Chloride deficiency is usually minor and does not require treatment. Thiazides increase urinary excretion of magnesium, which can lead to hypomagnesemia.

Thiazides can also reduce the excretion of calcium in the urine and, as a result, cause a slight transient increase in its level in the blood plasma. Significant hypercalcemia may be a manifestation of latent hyperparathyroidism. Thiazides should be discontinued before testing parathyroid function.

Hyperkalemia

Some patients taking ACE inhibitors, including lisinopril, experienced an increase in serum potassium concentrations. Risk factors for hyperkalemia include renal failure, diabetes mellitus, concomitant use of potassium-sparing diuretics, potassium-containing dietary supplements or potassium-containing salt substitutes or other drugs that cause an increase in serum potassium concentrations (for example, heparin, trimethoprim). If taking the above-mentioned drugs during treatment with ACE inhibitors is considered necessary, regular monitoring of serum potassium levels is recommended.

Monitoring blood electrolyte levels is particularly important in patients receiving potassium-sparing diuretics and ACEIs or ARBs for heart failure. Also in such cases, the lowest effective doses of potassium-sparing diuretics and ACEIs/ARBs should be used. In case of hyperkalemia, suspension or discontinuation of treatment should be considered.

Diabetes

Patients taking oral antidiabetic agents or insulin should exercise close glycemic control, especially during the first month of treatment with ACE inhibitors.

Hypersensitivity/angioedema

Angioedema of the face, extremities, lips, tongue, epiglottis, vocal cords and/or larynx has been observed in isolated cases in patients treated with ACE inhibitors, including lisinopril. Angioedema may develop at any time during treatment. In this case, the use of lisinopril should be stopped immediately, appropriate treatment should be administered and the patient should be monitored until symptoms disappear completely.

Even in cases where swelling is limited to the tongue and there are no signs of respiratory distress, patients may require long-term observation as treatment with antihistamines and corticosteroids may not be sufficient.

Very rarely, deaths due to angioedema of the larynx or tongue have been reported. If swelling extends to the tongue, vocal cords, or larynx, airway obstruction may occur, especially in patients who have previously had respiratory surgery. In such cases, emergency treatment measures (administration of adrenaline (epinephrine) and/or maintaining airway patency) should be taken immediately. The patient should be under close medical supervision until symptoms disappear completely and permanently.

Angioedema with the use of ACE inhibitors occurred more often in representatives of the Negroid race than in patients of other races.

Patients with a history of angioedema not related to ACE inhibitor therapy may have an increased risk of developing it when using ACE inhibitors.

Patients receiving thiazides may experience hypersensitivity reactions (with or without a history of allergies or bronchial asthma). The use of the drug may worsen the course of connective tissue diseases, incl. systemic lupus erythematosus.

Anaphylactoid reactions during desensitization therapy

In patients receiving ACE inhibitors, prolonged anaphylactoid reactions developed during desensitizing therapy with allergens (for example, hymenoptera venom). By abstaining from taking ACE inhibitors during desensitization, such reactions can be avoided, but accidental repeated administration of ACE inhibitors again provoked the development of anaphylactoid reactions.

Neutropenia / agranulocytosis / thrombocytopenia / anemia

Cases of neutropenia/agranulocytosis, thrombocytopenia and anemia have been reported in patients taking ACE inhibitors. With normal renal function and in the absence of any other predisposing factors, neutropenia rarely develops. Neutropenia and agranulocytosis are reversible after discontinuation of ACE inhibitors.

Lisinopril should be used with particular caution in patients with diffuse connective tissue diseases, those being treated with immunosuppressants, allopurinol or procainamide, or a combination of these complicating factors, especially in the presence of pre-existing renal impairment.

Some of these patients developed severe infections that sometimes did not respond to intensive antibiotic therapy. When using lisinopril in such patients, it is recommended that the white blood cell count be periodically monitored, and patients should be warned to inform the physician of any signs of infection.

Choroidal effusion, acute myopia and secondary glaucoma

Hydrochlorothiazide, which is part of the drug, can cause an idiosyncratic reaction, which leads to the appearance of choroidal effusion with a visual field defect, the development of acute transient myopia and acute angle-closure glaucoma. Symptoms are characterized by an acute onset of decreased visual acuity and/or ocular pain and usually develop within hours to several weeks from the start of hydrochlorothiazide treatment.

Untreated acute glaucoma can lead to permanent vision loss. The first step is to stop using hydrochlorothiazide as soon as possible. Prompt medical or surgical treatment should subsequently be considered if intraocular pressure remains uncontrolled. A history of allergy to sulfonamides or penicillins may be a risk factor for the development of acute angle-closure glaucoma.

Ethnic characteristics

Blacks taking ACE inhibitors were more likely to experience angioedema compared to patients of other races. As with other ACE inhibitors, the antihypertensive effect of lisinopril is less pronounced in patients of the Black race than in patients of other races, possibly due to the greater prevalence of individuals with low blood renin levels among hypertensive Black patients.

Cough

During treatment with ACE inhibitors, the occurrence of a non-productive persistent cough has been reported, which resolves after discontinuation of the drug. Cough caused by ACE inhibitors should be differentiated from cough caused by other diseases.

Primary hyperaldosteronism

In patients suffering from primary hyperaldosteronism, ACE inhibitors are ineffective and should not be used in this group of patients.

Lithium

Concomitant use of lithium and lisinopril is generally not recommended.

Elderly patients

According to clinical studies, the effectiveness and tolerability of simultaneous use of lisinopril and hydrochlorothiazide were similar in both elderly patients and younger patients with arterial hypertension.

No dosage adjustment is required for elderly patients. If an elderly patient experiences decreased renal function, the initial dose of lisinopril should be adjusted (see "Renal failure").

Pregnancy

You should not start taking ACE inhibitors during pregnancy. If continued therapy with ACE inhibitors is considered necessary, patients planning pregnancy should be switched to alternative antihypertensive therapy with drugs that have an established safety profile for use during pregnancy. If pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately and, if necessary, alternative therapy should be initiated (see Sections “Contraindications” and “Use during pregnancy or lactation”).

Photosensitivity

Photosensitivity reactions have been reported during treatment with thiazides. If photosensitivity occurs during treatment, it is recommended to discontinue the drug. If the doctor believes that the drug needs to be re-prescribed, it is recommended to protect areas of the body exposed to sunlight or artificial UV radiation and limit exposure to the sun.

Anti-doping test

The hydrochlorothiazide contained in this medicine may cause a false positive result in a doping test.

The antihypertensive effect of hydrochlorothiazide may be enhanced after sympathectomy.

During treatment with Liprazide, alcohol consumption is not recommended.

Directions for use and dosage

Liprazide is taken orally, swallowing the tablets whole with a sufficient amount of liquid, regardless of meals, but preferably at the same time of day. If necessary, the tablet can be divided into parts.

The dosage and duration of treatment with the drug are determined by the doctor individually for each patient. Usually prescribed 5-10 mg 1 time/day. If after 1-2 weeks of taking Liprazide the therapeutic effect is not sufficiently pronounced, the dose is gradually increased. The recommended maintenance dose is 20 mg once a day.

The maximum permissible daily dose for patients with normal renal function is 80 mg.

The initial dose for patients with impaired renal function (creatinine clearance more than 30 ml/minute) and patients with renovascular hypertension is 2.5 mg 1 time per day.

Before prescribing Liprazide, the doctor must provide the patient with complete information about the symptoms of angioedema.

Liprazid 20 tablets 20mg/12.5mg No. 10x3

Name

Liprazid 20 tablets 20 mg 12.5 mg No. 10x3

Basic physical and chemical properties

Liprazid 10 is a round tablet with a biconvex surface, light yellow in color with a brownish tint. Marbling and inclusions from yellow to brown are allowed on the surface of the tablets. Liprazid 20 is a round tablet with a biconvex surface, pink in color. Marbling and inclusions of red-brown color are allowed on the surface of the tablets.

Compound

active ingredients: lisinopril and hydrochlorothiazide; composition: 1 tablet of Liprazide 10 contains lisinopril - 10 mg, which corresponds to lisinopril dihydrate - 10.89 mg and hydrochlorothiazide - 12.5 mg; 1 tablet of Liprazide 20 contains lisinopril - 20 mg, which corresponds to lisinopril dihydrate - 21.78 mg and hydrochlorothiazide - 12.5 mg; excipients: Liprazide 10 - mannitol (E 421), corn starch, magnesium stearate, yellow iron oxide (E 172), calcium hydrogen phosphate dihydrate. Liprazide 20 - mannitol (E 421), corn starch, magnesium stearate, red iron oxide (E 172), calcium hydrogen phosphate dihydrate.

Pharmacotherapeutic group

Drugs affecting the renin-angiotensin system. ACE inhibitors in combination with other drugs. ACE inhibitors and diuretics. ATS code C09B A03.

Indications

Mild to moderate arterial hypertension in patients whose condition is already adequately controlled by simultaneous administration of lisinopril and hydrochlorothiazide in the same doses as Liprazide.

Contraindications

Hypersensitivity to lisinopril, hydrochlorothiazide, other components of the drug or other ACE inhibitors; hypersensitivity to sulfonamide derivatives; history of hereditary or idiopathic angioedema (Quincke's edema); history of angioedema caused by taking ACE inhibitors; bilateral renal artery stenosis or renal artery stenosis of a single kidney; mitral or aortic stenosis, hypertrophic cardiomyopathy with severe hemodynamic disturbances; acute myocardial infarction with unstable hemodynamics; cardiogenic shock; severe renal (creatinine clearance

Precautionary measures

Non-melanoma skin cancer. Increased risk of non-melanoma skin cancer (NMSC)

basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)

with increasing cumulative dose of hydrochlorothiazide was demonstrated in two pharmacoepidemiological studies based on data from the Danish National Cancer Registry. The photosensitizing effect of hydrochlorothiazide may act as a possible mechanism for the development of this pathology. Patients taking hydrochlorothiazide alone or in combination with other drugs should be informed of the risk of developing NMSC, especially with long-term use, the need for regular skin checks, and to promptly report any suspicious skin growths, any changes in skin lesions or moles . To reduce the risk of developing skin cancer, patients should be advised of possible preventative measures, such as limiting exposure to sunlight and UV radiation, and if exposed, the need for adequate skin protection. It is necessary to examine suspicious skin lesions as soon as possible, including histological examination of biopsy material. Patients with a history of NMSC may also need to reconsider the use of hydrochlorothiazide. Symptomatic hypotension and previous treatment with diuretics. In patients with dehydration and electrolyte imbalance due to previous diuretic treatment, or with dehydration of a different origin (excessive sweating, prolonged vomiting, profuse diarrhea), symptomatic arterial hypotension may occur after taking Liprazide. To prevent it, the use of diuretics must be stopped 2-3 days before starting Liprazide treatment. If this is not possible, treatment should begin with a dose of 5 mg (in terms of lisinopril). In patients at increased risk of symptomatic hypotension, treatment should be initiated under medical supervision and with periodic monitoring of serum electrolyte levels. In case of arterial hypotension, the patient should be in a supine position, and if necessary, saline solution should be administered intravenously. A temporary hypotensive reaction is not a contraindication to further treatment; to further restore the effective blood volume and blood pressure (BP), it is necessary to reduce the dose or switch to monotherapy with one of the active components of the drug. When changing the dose, monitoring should be especially careful. Electrolyte imbalance. As with any diuretic treatment, patients should periodically determine serum electrolyte levels. Thiazides, including hydrochlorothiazide, can cause water and electrolyte imbalance (hypokalemia, hyponatremia, hypochloremic alkalosis). Symptoms of water and electrolyte imbalance include dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain or cramps, muscle weakness, hypotension, oliguria, tachycardia, and gastrointestinal disorders such as nausea and vomiting. In hot weather, patients prone to edema may develop hyponatremia. Chloride deficiency is usually mild and does not require treatment. Thiazides may increase renal excretion of magnesium, which may lead to hypomagnesemia. Aortic stenosis/hypertrophic cardiomyopathy. ACE inhibitors should be prescribed with caution to patients with left ventricular outflow tract obstruction. Prescribe with caution to patients with coronary heart disease or cerebrovascular disease, since a pronounced decrease in blood pressure can cause myocardial infarction or cerebrovascular stroke. Surgery/general anesthesia. Caution should be exercised when using Liprazide in patients who are planning to undergo surgery under anesthesia, since during major surgical interventions and the use of other drugs that cause a decrease in blood pressure, lisinopril, by blocking the formation of angiotensin II, can cause a pronounced, unpredictable decrease in blood pressure. Hypotension of this origin can be eliminated by compensation of intravascular fluid. Metabolic and endocrine effects. Thiazide therapy may reduce glucose tolerance. Doses of antidiabetic agents, including insulin, may need to be adjusted. Thiazides may reduce urinary calcium excretion and cause a transient and slight increase in serum calcium. Hypercalcemia may indicate hidden hyperparathyroidism. Thiazides should be discontinued before parathyroid function tests are performed. Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy. Thiazide diuretic therapy may precipitate hyperuricemia and/or gout in some patients. However, lisinopril may increase the excretion of uric acid and thus may reduce the hyperuricemic effect of hydrochlorothiazide. Patients with diabetes mellitus. In diabetic patients taking oral antidiabetic agents or insulin, careful glycemic control should be exercised, especially during the first month of ACE inhibitor therapy. Manifestation of latent diabetes is possible. Hypersensitivity/angioedema. Angioedema of the face, upper and lower extremities, lips, tongue, epiglottis and/or larynx has rarely been reported in patients taking ACE inhibitors, including lisinopril. This can happen at any time during therapy. In such cases, the use of Liprazide should be stopped immediately, appropriate treatment should be administered and the patient should be closely monitored until symptoms disappear completely. Even in cases where swelling is limited only to the tongue and there are no signs of respiratory distress, the patient's condition should be monitored, since treatment with antihistamines and corticosteroids may not be sufficient. Very rarely, deaths due to angioedema of the larynx or tongue have been reported. If swelling extends to the tongue, vocal cords, or larynx, airway obstruction may occur, especially in patients who have previously undergone respiratory surgery. In such cases, it is necessary to take emergency treatment measures (administration of adrenaline (epinephrine) and/or maintaining airway patency). The patient should be under medical supervision until symptoms disappear completely and permanently. Patients with a history of angioedema not related to ACE inhibitor therapy may be at risk of developing angioedema while receiving an ACE inhibitor. Patients receiving thiazide therapy may experience hypersensitivity reactions (with or without a history of allergies or asthma). The use of the drug may worsen the course of connective tissue diseases, including systemic lupus erythematosus. Patients on hemodialysis. The use of lisinopril/hydrochlorothiazide is not indicated in patients with renal failure requiring hemodialysis. It is also not prescribed to patients with a transplanted kidney. The development of anaphylactic reactions has been reported in patients who underwent hemodialysis using high-precision membranes (for example AN 69) and simultaneously used ACE inhibitors. These patients may need to use a different type of dialysis membrane or a different class of antihypertensive drug. Anaphylactoid reactions during low-density lipoprotein (LDL) apheresis. Life-threatening anaphylactoid reactions have rarely developed in patients treated with ACE inhibitors during low-density lipoprotein (LDL) apheresis using dextran sulfate absorption. To avoid these reactions, ACE inhibitors should be suspended before each apheresis procedure. Anaphylactoid reactions during desensitizing therapy. Patients receiving ACE inhibitors during desensitization with an allergen from hymenoptera venom (for example, bee venom) developed anaphylactoid reactions. If such patients refrained from taking ACE inhibitors during desensitization, no reactions were observed, but accidental administration of ACE inhibitors provoked anaphylactoid reactions. Cough. A nonproductive/persistent cough is characteristic, which is observed when taking ACE inhibitors and disappears after discontinuation of therapy. Cough caused by an ACE inhibitor must be differentiated from cough caused by other diseases. Salt-free diet. The drug should be prescribed with caution to patients on a salt-free diet. Renal dysfunction. Thiazides may be inappropriate diuretics for use in patients with renal impairment and are ineffective when creatinine clearance is 30 mL/min or lower (moderate to severe renal impairment). Liprazide should not be administered to patients with renal impairment (creatinine clearance less than 80 ml/min), unless dose titration of the individual active substances of the drug is used to achieve an acceptable dose that is present in the combination. Some patients with arterial hypertension without obvious signs of damage to the blood vessels of the kidneys may experience a slight temporary increase in serum urea and creatinine levels, especially when lisinopril was used concomitantly with diuretics. This occurs more often in patients with pre-existing kidney dysfunction. This condition requires dose reduction and/or discontinuation of the diuretic and/or Liprazide. In some patients with bilateral renal artery stenosis or renal artery stenosis of a solitary kidney, ACE inhibitors increase serum urea and creatinine levels; Typically, these effects disappear after stopping the medications. The likelihood of such events is especially high in patients with renal failure. The presence of renovascular hypertension increases the risk of developing severe arterial hypotension and renal failure. Treatment of such patients should begin under medical supervision with low doses and subsequently with careful titration of the dose. Since diuretics may precipitate the condition described above, renal function should be carefully monitored during the first weeks of treatment with lisinopril/hydrochlorothiazide. Liver diseases. Thiazides should be used with caution in patients with impaired liver function or progressive liver disease, since minor changes in water-salt and electrolyte balance can cause sudden hepatic coma. Very rarely, a syndrome that begins with cholestatic jaundice or hepatitis and progresses to liver necrosis, sometimes fatal, has been associated with the use of ACE inhibitors. The mechanism of this syndrome is unknown. If patients taking ACE inhibitors develop jaundice or significantly increase the activity of liver enzymes, the drug should be discontinued and the patient should be kept under medical supervision until symptoms disappear. Elderly persons. Treatment begins with the lower limit of the dose of Liprazide (10 mg + 12.5 mg) due to the fact that the likelihood of deterioration in liver, kidney and heart function is higher due to concomitant diseases and the use of other medications. When selecting doses, safety precautions (monitoring renal function) should be observed. Neutropenia/agranulocytosis. Neutropenia/agranulocytosis, thrombocytopenia and anemia may develop in patients taking ACE inhibitors. With normal renal function and in the absence of complications, neutropenia rarely develops. Neutropenia and agranulocytosis are reversible and disappear after discontinuation of ACE inhibitors. Liprazide should be used with particular caution in patients with connective tissue disease with vascular manifestations, those receiving treatment with immunosuppressants, allopurinol or procainamide, or a combination of these factors, especially in the presence of pre-existing renal impairment. Some of these patients develop severe infections that sometimes do not respond to intensive antibiotic therapy. When using Liprazide in this group of patients, periodic monitoring of leukocytes is recommended, and the patient should be warned about the need to inform the doctor of any signs of infection. Hyperkalemia. In some patients, when taking ACE inhibitors, including lisinopril, an increase in serum potassium concentrations was noted. Risk factors for hyperkalemia include renal failure or diabetes mellitus, concomitant use of potassium-sparing diuretics, dietary supplements containing potassium or potassium salt substitutes, or other drugs that cause an increase in serum potassium concentrations (eg, heparin). If taking the above drugs during treatment with ACE inhibitors is determined to be necessary, regular monitoring of serum potassium levels is recommended. Lithium. Concomitant use of lithium and lisinopril is generally not recommended. Dual blockade of the renin-angiotensin-aldosterone system (RAAS). Double blockade of the RAAS with simultaneous use of ACE inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), direct renin inhibitors (for example, aliskiren) is associated with an increased risk of arterial hypotension, hyperkalemia, and renal dysfunction (including acute renal disease). failure) compared to monotherapy. If this combination is necessary, blood pressure, renal function and blood electrolytes should be carefully monitored in patients taking lisinopril and other drugs that affect the RAAS. The use of aliskiren in combination with BRAN or ACE inhibitors is contraindicated in patients with diabetes mellitus or impaired renal function (GFR

Children

Contraindicated for children.

Use during pregnancy or breastfeeding

The use of the drug during pregnancy is contraindicated, since hydrochlorothiazide reduces maternal plasma volume, uteroplacental blood supply and penetrates the placental barrier. There is a risk of the fetus developing fetal or neonatal jaundice, thrombocytopenia and other harmful effects. Epidemiological data on the risk of teratogenicity when taking ACE inhibitors in the first trimester of pregnancy do not allow us to make a final conclusion, but a slight increase in risk cannot be excluded. Except in cases where therapy with ACE inhibitors should be considered irreplaceable and justified, patients planning pregnancy should be switched to alternative antihypertensive therapy with drugs with a proven safety profile for pregnant women. If pregnancy occurs, the ACE inhibitor should be discontinued immediately and, if necessary, alternative antihypertensive therapy should be prescribed. Newborns whose mothers took ACE inhibitors should be carefully monitored due to the possibility of arterial hypotension, oliguria and hyperkalemia developing in such newborns. Since there is no information regarding the use of lisinopril/hydrochlorothiazide during breastfeeding, the drug is contraindicated in women who are breastfeeding. Alternative antihypertensive therapy with drugs with a proven safety profile is recommended for breastfeeding women, especially when feeding a newborn or premature infant.

The ability to influence the reaction rate when driving a vehicle or working with other mechanisms

Due to the risk of adverse reactions such as dizziness (especially at the beginning of treatment), confusion, and arterial hypotension, it is not recommended to drive vehicles or operate other mechanisms until the patient’s individual response is determined.

Interaction with other drugs

Lisinopril with: direct renin inhibitors (for example, aliskiren-containing drugs), ARB II: the risk of arterial hypotension, hyperkalemia, and renal dysfunction (including acute renal failure) increases. Combination of ACE inhibitors, incl. lisinopril, with aliskiren-containing drugs is contraindicated in patients with diabetes mellitus or impaired renal function (GFR

Directions for use and dosage

The drug is prescribed taking into account the doses of lisinopril or hydrochlorothiazide, which were used in monotherapy. The dose and duration of treatment are selected individually depending on the therapeutic effect and severity of the disease. The usual dose is 1 tablet of Liprazide 10 or Liprazide 20 per day. The drug should be taken at approximately the same time every day. If the desired therapeutic effect is not achieved within 2-4 weeks, the dose should be increased to 2 tablets. The maximum daily dose (in terms of lisinopril) is 40 mg. Renal failure Liprazide 10 or Liprazide 20 should not be used as initial therapy in these patients. Thiazides are not usually used in patients with impaired renal function; they are not effective when creatinine clearance is 30 ml/min or lower (i.e., with moderate to severe renal impairment). In patients with creatinine clearance > 30 and

Overdose

Symptoms associated with an overdose of ACE inhibitors: arterial hypotension, circulatory shock, electrolyte disturbances, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety, cough. To treat an overdose, administration of saline is recommended. In case of arterial hypotension, the patient should be placed on his back with his legs elevated. If necessary, infusion of angiotensin II and/or intravenous catecholamines is possible. If the drug has been used recently, measures should be taken to eliminate lisinopril (stimulating vomiting, gastric lavage, administration of absorbents and sodium sulfate). Lisinopril can be removed from the body by hemodialysis. Therapy with cardiac stimulants is indicated in the event of bradycardia that is resistant to treatment with other therapeutic agents. Vital signs, serum electrolyte balance, and creatinine concentrations should be continuously monitored. Symptoms caused by an overdose of hydrochlorothiazide: increased diuresis, depression of consciousness (including coma), convulsions, paresis, arrhythmia, renal failure. Bradycardia or vagal reactions can be eliminated by the use of atropine. In the case of concomitant use of digitalis drugs, hypokalemia may develop, which increases the risk of arrhythmia.

Best before date

3 years. The expiration date is the last day of the month indicated on the packaging. Do not use the drug after the expiration date indicated on the package!

Storage conditions

Store in original packaging to protect from light at temperatures not exceeding 25 °C. If the blister pack is removed from the pack, it must be protected from light. Keep out of the reach of children.

Package

10 tablets in a blister made of polyvinyl chloride film and aluminum foil, coated on one side with thermovarnish and printed on the other side. 3 blisters along with instructions for medical use of the drug in a cardboard pack.

Vacation conditions

On prescription.

Side effects

• Gastrointestinal tract and liver: dryness of the oral mucosa, pain in the epigastric region, digestive disorders, loss of appetite, nausea, vomiting, stool disorders; in isolated cases - changes in taste, jaundice, pancreatitis, hepatitis;
• Central and peripheral nervous system: increased fatigue, headache, sleep/wake disturbances, dizziness, emotional lability, increased irritability, weakness, paresthesia, convulsions; in isolated cases - asthenic syndrome, confusion;
• Cardiovascular system and hematopoietic system: cardiac arrhythmia, thrombocytopenia, feeling of pain and pressure in the chest, excessive decrease in blood pressure, incl. orthostatic hypotension, neutropenia, anemia, agranulocytosis, leukopenia;
• Urinary system: anuria, uremia, renal dysfunction, acute renal failure;
• Laboratory indicators: eosinophilia, increased erythrocyte sedimentation rate, leukocytosis, changes in potassium levels in the blood, decreased glucose tolerance, increased activity of liver enzymes, decreased levels of chlorine, magnesium and sodium in the blood, increased levels of creatinine, calcium, bilirubin, glycerides, urea, cholesterol;
• Allergic reactions: alopecia, urticaria, photosensitivity, itching, skin rash, bronchospasm, Quincke's edema;
• Other: respiratory rhythm disturbance, cough, increased sweating, pain in muscles and joints, decreased potency; with long-term treatment – ​​gout.

Drug interactions

Possible interaction reactions when Liprazide is used simultaneously with other drugs:

• Hypoglycemic drugs: reduction of their therapeutic effects;
• Cyclosporine, sodium chloride solution, potassium-sparing diuretics and potassium preparations, non-steroidal anti-inflammatory drugs, estrogens: decreased effectiveness of Liprazide (potassium preparations, potassium-sparing diuretics, indomethacin and cyclosporine also increase the risk of hyperkalemia);
• Thiazide and loop diuretics: increased hypotensive effect of the drug;
• Tetracyclines, antacids, enterosorbents, cholestipol, cholestyramine: decreased absorption of the active substances of Liprazid;
• Digoxin: increased toxicity;
• Lithium preparations, amantadine: slowing their elimination;
• Tubocurarine: enhancing its action;
• Methyldopa: risk of intravascular hemolysis;
• Barbiturates, ethyl alcohol, narcotic drugs: risk of developing hypokalemia and orthostatic hypotension;
• Cardiac glycosides: risk of hypokalemia;
• Amiodarone: likelihood of developing arrhythmia;
• Allopurinol, procainamide, systemic glucocorticosteroids, cytostatics, immunosuppressive drugs: risk of developing leukopenia;
• Non-depolarizing muscle relaxants: enhancing their effects.