Noliprel A Bi-forte tablets 10 mg + 2.5 mg 30 pcs. in Moscow

Compound

The drug Noliprel is offered in several different forms. All variations of the drug include perindopril and indapamide . Combined Noliprel contain 2 mg of perindopril and 0.625 mg of indapamide. The composition of Noliprel Forte includes 4 mg of perindopril and 1.25 mg of indapamide. Noliprel A contains 2.5 mg of perindopril and 0.625 mg of indapamide.
In this drug, perindopril is associated with the amino acid arginine, which has a beneficial effect on the condition of the cardiovascular system. Noliprel A Forte tablets contain 5 mg of perindopril and 1.25 mg of indapamide. Noliprel A Bi-forte contains 10 mg of perindopril and 2.5 mg of indapamide.

As additional substances in the composition of the drug Noliprel there is magnesium stearate, lactose monohydrate, colloidal hydrophobic silicon dioxide, microcrystalline cellulose.

NOLIPREL A FORTE film-coated tablets 5mg+1.25mg No. 30

The use of Noliprel® A forte 5 mg + 1.25 mg is not accompanied by a significant reduction in the frequency of side effects, with the exception of hypokalemia, compared with perindopril and indapamide at the lowest approved doses (see “Side effects”). When starting therapy with two antihypertensive drugs that the patient has not previously received, an increased risk of developing idiosyncrasies cannot be excluded. Careful monitoring of the patient can minimize this risk. Impaired renal function Therapy is contraindicated in patients with severe renal failure (Cl creatinine less than 30 ml/min). In some patients with arterial hypertension without previous obvious renal impairment, laboratory signs of functional renal failure may appear during therapy. In this case, treatment should be stopped. In the future, you can resume combination therapy using low doses of drugs, or use drugs in monotherapy. Such patients require regular monitoring of potassium and creatinine levels in the blood serum - 2 weeks after the start of therapy and every 2 months thereafter. Renal failure occurs more often in patients with severe chronic heart failure or underlying renal impairment, incl. with renal artery stenosis. Hypotension and fluid and electrolyte imbalance Hyponatremia is associated with a risk of sudden development of arterial hypotension (especially in patients with arterial stenosis of a solitary kidney and bilateral renal artery stenosis). Therefore, during dynamic monitoring of patients, attention should be paid to possible symptoms of dehydration and decreased levels of electrolytes in the blood plasma, for example, after diarrhea or vomiting. Such patients require regular monitoring of plasma electrolyte levels. In case of severe arterial hypotension, intravenous administration of 0.9% sodium chloride solution may be required. Transient arterial hypotension is not a contraindication for continued therapy. After restoration of blood volume and blood pressure, therapy can be resumed using low doses of drugs, or drugs can be used as monotherapy. Potassium levels The combined use of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal failure. As in the case of the combined use of an antihypertensive drug and a diuretic, regular monitoring of the level of potassium in the blood plasma is necessary. Excipients It should be taken into account that the excipients of the drug include lactose monohydrate. Noliprel® A forte should not be prescribed to patients with hereditary galactose intolerance, lactase deficiency and glucose-galactose malabsorption. Lithium preparations The simultaneous use of a combination of perindopril and indapamide with lithium preparations is not recommended (see “Contraindications”, “Interaction”). Perindopril Neutropenia/agranulocytosis The risk of developing neutropenia while taking ACE inhibitors is dose-dependent and depends on the drug taken and the presence of concomitant diseases. Neutropenia rarely occurs in patients without concomitant diseases, but the risk increases in patients with impaired renal function, especially against the background of systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma). After discontinuation of ACE inhibitors, signs of neutropenia disappear on their own. To prevent the development of such reactions, it is recommended to strictly follow the recommended dose. When prescribing ACE inhibitors to this group of patients, the benefit/risk factor should be carefully assessed. Angioedema (Quincke's edema) When taking ACE inhibitors, incl. and perindopril, in rare cases, the development of angioedema of the face, extremities, lips, tongue, glottis and/or larynx may occur. If symptoms appear, perindopril should be discontinued immediately and the patient should be observed until signs of edema completely disappear. If the swelling affects only the face and lips, it usually resolves on its own, although antihistamines may be used to treat symptoms. Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, glottis, or larynx can lead to airway obstruction. If such symptoms appear, you should immediately administer subcutaneous epinephrine (adrenaline) at a dilution of 1:1000 (0.3 or 0.5 ml) and/or ensure airway patency. Patients with a history of angioedema, not associated with taking ACE inhibitors, may have an increased risk of developing it when taking drugs of this group (see “Contraindications”). In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. Anaphylactoid reactions during desensitization There are isolated reports of the development of long-term life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with the venom of hymenoptera insects (bees, wasps). ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. Prescription of an ACE inhibitor should be avoided in patients receiving immunotherapy with hymenoptera venom. However, an anaphylactoid reaction can be avoided by temporarily discontinuing the ACE inhibitor at least 24 hours before the procedure. Anaphylactoid reactions during LDL apheresis In rare cases, life-threatening anaphylactoid reactions may develop in patients receiving ACE inhibitors during LDL apheresis using dextran sulfate, or in patients undergoing hemodialysis using high-flow membranes. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be temporarily discontinued at least 24 hours before the apheresis procedure. Cough During therapy with an ACE inhibitor, a dry cough may occur. The cough persists for a long time while taking drugs of this group and disappears after their discontinuation. If a patient develops a dry cough, one should be aware of the possible iatrogenic nature of this symptom. If the attending physician believes that ACE inhibitor therapy is necessary for the patient, the drug may be continued. Children and adolescents The drug should not be prescribed to children and adolescents under the age of 18 years due to the lack of data on the effectiveness and safety of the use of perindopril as monotherapy or as part of combination therapy in patients of this age group. Risk of arterial hypotension and/or renal failure (in patients with heart failure, water-electrolyte imbalance, etc.) In some pathological conditions, significant activation of the RAAS system may be observed, especially with severe hypovolemia and a decrease in the level of electrolytes in the blood plasma (against the background of salt-free diet or long-term use of diuretics), in patients with initially low blood pressure, with bilateral renal artery stenosis or with stenosis of the artery of a single kidney, chronic heart failure or cirrhosis of the liver with edema and ascites. The use of an ACE inhibitor causes a blockade of this system and therefore may be accompanied by a sharp decrease in blood pressure and/or an increase in plasma creatinine levels, indicating the development of functional renal failure. These phenomena are more often observed when taking the first dose of the drug or during the first two weeks of therapy. Sometimes these conditions develop acutely and during other periods of therapy. In such cases, when resuming therapy, it is recommended to use the drug at a lower dose and then gradually increase the dose. Elderly patients Before starting to take the drug, it is necessary to assess the functional activity of the kidneys and the concentration of potassium in the blood plasma. At the beginning of therapy, the dose of the drug is selected taking into account the degree of reduction in blood pressure, especially in the case of dehydration and loss of electrolytes. Such measures help to avoid a sharp decrease in blood pressure. Atherosclerosis The risk of arterial hypotension exists in all patients, however, special care should be taken when using the drug in patients with coronary artery disease and cerebrovascular insufficiency. In such patients, treatment should be started with low doses. Patients with renovascular hypertension The treatment method for renovascular hypertension is revascularization. However, the use of ACE inhibitors has a beneficial effect in this category of patients, both awaiting surgery and in cases where surgery is not possible. Treatment with Noliprel® A forte in patients with diagnosed or suspected bilateral renal artery stenosis or stenosis of the artery of a single kidney should be started with a low dose of the drug in a hospital setting, monitoring renal function and potassium concentration in the blood plasma. Some patients may develop functional renal failure, which disappears when the drug is discontinued. Other risk groups In persons with severe heart failure (stage IV) and patients with insulin-dependent diabetes mellitus (risk of spontaneous increase in potassium concentration), treatment should begin with a low dose of the drug and under constant medical supervision. Patients with arterial hypertension and coronary artery disease should not stop taking beta-blockers: ACE inhibitors should be used together with beta-blockers. Anemia Anemia can develop in patients after kidney transplantation or in people on hemodialysis. In this case, the decrease in hemoglobin concentration is greater, the higher its initial value. This effect does not appear to be dose-dependent, but may be related to the mechanism of action of ACE inhibitors. A slight decrease in hemoglobin concentration occurs during the first 6 months, then it remains stable and is completely restored after discontinuation of the drug. In such patients, treatment can be continued, but hematological tests should be performed regularly. Surgery/general anesthesia The use of ACE inhibitors in patients undergoing surgery under general anesthesia can lead to a marked decrease in blood pressure, especially when using general anesthesia agents that have a hypotensive effect. It is recommended to stop taking long-acting ACE inhibitors, incl. perindopril, the day before surgery. It is necessary to warn the anesthesiologist that the patient is taking ACE inhibitors. Aortic stenosis/hypertrophic cardiomyopathy ACE inhibitors should be prescribed with caution to patients with left ventricular outflow tract obstruction. Liver failure In rare cases, cholestatic jaundice occurs while taking ACE inhibitors. As this syndrome progresses, liver necrosis may rapidly develop, sometimes with death. The mechanism of development of this syndrome is unclear. If jaundice appears or a significant increase in the activity of liver enzymes while taking ACE inhibitors, you should stop taking the drug and consult a doctor (see “Side effects”). Indapamide In the presence of liver dysfunction, taking thiazide and thiazide-like diuretics can lead to the development of hepatic encephalopathy. In this case, you should immediately stop taking the drug. Water-electrolyte balance Content of sodium ions in blood plasma. Before starting treatment, it is necessary to determine the content of sodium ions in the blood plasma. While taking the drug, this indicator should be regularly monitored. All diuretics can cause hyponatremia, which sometimes leads to serious complications. Hyponatremia at the initial stage may not be accompanied by clinical symptoms, so regular laboratory monitoring is necessary. More frequent monitoring of sodium ion levels is indicated for patients with liver cirrhosis and the elderly (see “Side effects” and “Overdose”). Content of potassium ions in blood plasma. Therapy with thiazide and thiazide-like diuretics is associated with a risk of hypokalemia. Hypokalemia (less than 3.4 mmol/l) should be avoided in the following categories of high-risk patients: elderly people, debilitated patients or those receiving concomitant drug therapy, patients with liver cirrhosis, peripheral edema or ascites, coronary artery disease, heart failure. Hypokalemia in these patients enhances the toxic effect of cardiac glycosides and increases the risk of developing arrhythmias. The high-risk group also includes patients with an increased QT interval, and it does not matter whether this increase is caused by congenital causes or the effect of drugs. Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, especially arrhythmias, which can be fatal. In all the cases described above, more regular monitoring of the content of potassium ions in the blood plasma is necessary. The first measurement of potassium ion concentration should be carried out within the first week from the start of therapy. If hypokalemia is detected, appropriate treatment should be prescribed. Content of calcium ions in blood plasma. Thiazide and thiazide-like diuretics reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in the concentration of calcium in the blood plasma. Severe hypercalcemia may be a consequence of previously undiagnosed hyperparathyroidism. Before studying the function of the parathyroid gland, you should stop taking diuretics. Glucose content in blood plasma. It is necessary to monitor blood glucose levels in patients with diabetes mellitus, especially in the presence of hypokalemia. Uric acid. In patients with elevated levels of uric acid in the blood plasma during therapy, the frequency of gout attacks may increase. Diuretics and kidney function. Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (plasma creatinine in adults below 25 mg/l or 220 µmol/l). At the beginning of diuretic treatment in patients, due to hypovolemia and hyponatremia, a temporary decrease in glomerular filtration rate and an increase in the concentration of urea and creatinine in the blood plasma may be observed. This transient functional renal failure is not dangerous for patients with unchanged renal function, but its severity may increase in patients with renal failure. Photosensitivity While taking thiazide and thiazide-like diuretics, cases of photosensitivity reactions have been reported. If photosensitivity reactions develop while taking the drug, treatment should be discontinued. If it is necessary to continue diuretic therapy, it is recommended to protect the skin from exposure to sunlight or artificial UV rays. Athletes Indapamide may give a positive reaction during doping control. Impact on the ability to drive a car or perform work that requires increased speed of physical and mental reactions. The effect of the substances included in the drug Noliprel® A forte does not lead to disturbances in psychomotor reactions. However, some people may develop different individual reactions in response to lowering blood pressure, especially at the beginning of therapy or when other antihypertensive drugs are added to therapy. In this case, the ability to drive a car or operate other machinery may be reduced.

pharmachologic effect

Noliprel is a combination drug that contains perindopril (an angiotensin-converting factor inhibitor) and indapamide (a diuretic that is part of the sulfonamide group).

The pharmacological effect of a drug is determined by a combination of some of the effects of these components. In this combination, both components mutually increase the effect. Noliprel is an antihypertensive drug that effectively lowers both diastolic and systolic blood pressure. The severity of the effect depends on the dose. After taking the drug, there is no rapid heartbeat. The clinical effect is observed 1 month after treatment was started. The antihypertensive effect lasts for one day. After therapy is suspended, the patient does not experience withdrawal symptoms. During treatment, the severity of left ventricular hypertrophy decreases, and the degree of total precardiac and postcardiac load decreases. Large vessels become more elastic, the walls of small vessels are restored. The medicine has no effect on the metabolic processes that occur in the body.

Perindopril reduces the level of aldosterone secretion, resulting in increased renin activity in the blood. Blood pressure decreases in people with different levels of renin . Under the influence of this component, blood vessels dilate.

When taking the drug, the likelihood of hypokalemia . The mechanism of action of indapamide is similar to thiazide diuretics: urination and excretion of sodium and chloride ions in the urine will increase.

Vascular hyperreactivity decreases under the influence of adrenaline. The amount of lipids in the blood does not change.

Noliprel® a

Noliprel® A

The use of Noliprel® A is not accompanied by a significant reduction in the frequency of side effects, with the exception of hypokalemia, compared with perindopril and indapamide at the lowest approved doses. When initiating therapy with two antihypertensive drugs that the patient has not previously received, an increased risk of idiosyncrasy cannot be excluded. To minimize this risk, careful monitoring of the patient's condition should be carried out.

Kidney failure

In patients with severe renal failure (creatinine clearance <30 ml/min), this combination is contraindicated.

In some patients with arterial hypertension without previous renal impairment during treatment with Noliprel A, laboratory signs of functional renal failure may appear. In this case, treatment should be stopped. In the future, you can resume combination therapy using low doses of drugs, or use drugs in monotherapy. Such patients require regular monitoring of potassium and creatinine levels in the blood serum - 2 weeks after the start of therapy and every 2 months thereafter. Renal failure occurs more often in patients with severe chronic heart failure or underlying renal impairment, incl. with renal artery stenosis.

Arterial hypotension and water-electrolyte imbalance

Hyponatremia is associated with a risk of sudden development of arterial hypotension (especially in patients with arterial stenosis of a solitary kidney and bilateral renal artery stenosis). Therefore, during dynamic monitoring of patients, attention should be paid to possible symptoms of dehydration and decreased levels of electrolytes in the blood plasma, for example, after diarrhea or vomiting. Such patients require regular monitoring of plasma electrolyte levels. In case of severe arterial hypotension, intravenous administration of 0.9% sodium chloride solution may be required.

Transient arterial hypotension is not a contraindication for continued therapy. After restoration of blood volume and blood pressure, therapy can be resumed using low doses of drugs, or drugs can be used as monotherapy.

Potassium content

The combination of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal failure. As with any antihypertensive drug taken in combination with a diuretic, plasma potassium levels should be regularly monitored during treatment with this combination.

Lithium preparations

The simultaneous use of a combination of perindopril and indapamide with lithium preparations is not recommended.

Excipients

It should be taken into account that the excipients of the drug include lactose monohydrate. Noliprel® A should not be prescribed to patients with hereditary galactose intolerance, lactase deficiency and glucose-galactose malabsorption.

Perindopril

Neutropenia/agranulocytosis

The risk of developing neutropenia while taking ACE inhibitors is dose-dependent and depends on the drug taken and the presence of concomitant diseases. Neutropenia rarely occurs in patients without concomitant diseases, but the risk increases in patients with impaired renal function, especially against the background of systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma). After discontinuation of ACE inhibitors, signs of neutropenia disappear on their own. To avoid the development of such reactions, it is recommended to strictly follow the recommended dose. When prescribing ACE inhibitors to this group of patients, the benefit/risk factor should be carefully weighed.

Angioedema (Quincke's edema)

In rare cases, during therapy with ACE inhibitors, incl. perindopril, angioedema of the face, extremities, mouth, tongue, pharynx and/or larynx develops. In such a situation, you should immediately stop taking perindopril and monitor the patient's condition until the swelling completely disappears. If the swelling affects only the face and mouth, the symptoms usually go away without special treatment, but antihistamines can be used to more quickly relieve symptoms.

Angioedema, which is accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, pharynx, or larynx can lead to airway obstruction. In this case, you should immediately administer epinephrine (adrenaline) subcutaneously at a dose of 1:1000 (0.3 to 0.5 ml) and take other emergency measures. Patients with a history of angioedema not associated with taking ACE inhibitors have an increased risk of developing angioedema while taking these drugs.

In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors.

Anaphylactic reactions during desensitization

There are isolated reports of the development of long-term, life-threatening anaphylactic reactions in patients receiving ACE inhibitors during desensitizing therapy with hymenoptera insect venom (including bee and aspen). ACE inhibitors should be prescribed with caution to patients prone to allergic reactions and undergoing desensitization procedures. Prescribing the drug to patients receiving immunotherapy with hymenoptera venom should be avoided. However, anaphylactic reactions can be avoided by temporarily discontinuing the drug at least 24 hours before starting a course of desensitizing therapy.

Anaphylactic reactions during LDL apheresis

In rare cases, life-threatening anaphylactic reactions may occur in patients receiving ACE inhibitors, during LDL apheresis using dextran sulfate, or in patients receiving hemodialysis using high-flow membranes. To prevent an anaphylactic reaction, ACE inhibitor therapy should be temporarily discontinued at least 24 hours before the apheresis procedure.

Cough

During therapy with an ACE inhibitor, a dry cough may occur. The cough persists for a long time while taking drugs of this group and disappears after their discontinuation. If a patient develops a dry cough, one should be aware of the possible iatrogenic nature of this symptom. If the attending physician believes that ACE inhibitor therapy is necessary for the patient, the drug may be continued.

Risk of arterial hypotension and/or renal failure (in case of heart failure, fluid and electrolyte imbalance)

In some pathological conditions, significant activation of the RAAS may be observed, especially with severe hypovolemia and a decrease in the level of plasma electrolytes (due to a salt-free diet or long-term use of diuretics), in patients with initially low blood pressure, with bilateral renal artery stenosis or with stenosis of the artery of a single kidney, chronic heart failure or cirrhosis of the liver with edema and ascites. The use of an ACE inhibitor causes a blockade of this system and therefore may be accompanied by a sharp decrease in blood pressure and/or an increase in plasma creatinine levels, indicating the development of functional renal failure. These phenomena are more often observed when taking the first dose of the drug or during the first two weeks of therapy. Sometimes these conditions develop acutely and during other periods of therapy. In such cases, when resuming therapy, it is recommended to use the drug at a lower dose and then gradually increase the dose.

Elderly patients

Before starting to take the drug, it is necessary to assess the functional activity of the kidneys and the concentration of potassium in the blood plasma. At the beginning of therapy, the dose of the drug is selected taking into account the degree of reduction in blood pressure, especially in the case of dehydration and loss of electrolytes. Such measures help to avoid a sharp decrease in blood pressure.

Patients with established atherosclerosis

The risk of arterial hypotension exists in all patients, but the drug should be used with extreme caution in patients with coronary artery disease or cerebrovascular insufficiency. In such cases, treatment should be started with a low dose.

Renovascular hypertension

The treatment method for renovascular hypertension is revascularization. However, the use of ACE inhibitors has a beneficial effect in this category of patients, both awaiting surgery and in cases where surgery is not possible. Treatment with Noliprel® A in patients with diagnosed or suspected bilateral renal artery stenosis or stenosis of the artery of a single kidney should begin with a low dose of the drug in a hospital setting, monitoring renal function and potassium concentration in the blood plasma. Some patients may develop functional renal failure, which disappears when the drug is discontinued.

Other risk groups

In patients with severe heart failure (stage IV) and patients with insulin-dependent diabetes mellitus (risk of spontaneous increase in potassium levels), treatment with the drug should be started with low doses and carried out under constant medical supervision.

In patients with arterial hypertension and heart failure, beta-blockers should not be discontinued: ACE inhibitors should be used together with beta-blockers.

Anemia

Anemia may develop in patients who have undergone a kidney transplant or in patients undergoing hemodialysis. The higher the initial hemoglobin level, the more pronounced its decrease. This effect does not appear to be dose-dependent, but may be related to the mechanism of action of ACE inhibitors. The decrease in hemoglobin content is insignificant, it occurs during the first 6 months of treatment, and then stabilizes. When treatment is discontinued, hemoglobin levels are completely restored. Treatment can be continued under monitoring of the peripheral blood picture.

Surgery/General anesthesia

The use of ACE inhibitors in patients undergoing surgery under general anesthesia can lead to a significant decrease in blood pressure, especially when using general anesthesia agents that have a hypotensive effect. It is recommended to stop taking long-acting ACE inhibitors, incl. perindopril, the day before surgery. It is necessary to warn the anesthesiologist that the patient is taking ACE inhibitors.

Aortic stenosis/Hypertrophic cardiomyopathy

ACE inhibitors should be prescribed with caution to patients with left ventricular outflow tract obstruction.

Liver failure

In rare cases, cholestatic jaundice occurs while taking ACE inhibitors. As this syndrome progresses, liver necrosis may rapidly develop, sometimes with death. The mechanism of development of this syndrome is unclear. If jaundice appears or a significant increase in the activity of liver enzymes while taking ACE inhibitors, the patient should stop taking the drug and consult a doctor.

Use in pediatrics

Noliprel® A should not be prescribed to children and adolescents under 18 years of age

, because the effectiveness and safety of use in this category of patients have not been established.

Indapamide

In the presence of liver dysfunction, taking thiazide and thiazide-like diuretics can lead to the development of hepatic encephalopathy. In this case, you should immediately stop taking the drug.

Water-electrolyte imbalance

Before starting treatment, it is necessary to determine the content of sodium ions in the blood plasma. While taking the drug, this indicator should be regularly monitored. All diuretics can cause hyponatremia, which sometimes leads to serious complications. Hyponatremia at the initial stage may not be accompanied by clinical symptoms, so regular laboratory monitoring is necessary. More frequent monitoring of sodium ion levels is indicated for patients with liver cirrhosis and the elderly

Therapy with thiazide and thiazide-like diuretics is associated with a risk of hypokalemia. Hypokalemia (less than 3.4 mmol/l) should be avoided in the following categories of high-risk patients: elderly people, debilitated patients or those receiving concomitant drug therapy, patients with liver cirrhosis, peripheral edema or ascites, coronary artery disease, heart failure. Hypokalemia in these patients enhances the toxic effect of cardiac glycosides and increases the risk of developing arrhythmias. The high-risk group also includes patients with an increased QT interval, and it does not matter whether this increase is caused by congenital causes or the effect of drugs.

Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, especially arrhythmias, which can be fatal. In all the cases described above, more regular monitoring of the content of potassium ions in the blood plasma is necessary. The first measurement of potassium ion concentration should be carried out within the first week from the start of therapy.

If hypokalemia is detected, appropriate treatment should be prescribed.

Thiazide and thiazide-like diuretics reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in the concentration of calcium in the blood plasma. Severe hypercalcemia may be a consequence of previously undiagnosed hyperparathyroidism. Before studying the function of the parathyroid gland, you should stop taking diuretics.

Blood glucose level

It is necessary to monitor blood glucose levels in patients with diabetes mellitus, especially in the presence of hypokalemia.

Uric acid

In patients with high levels of uric acid in the blood during treatment with Noliprel A, the incidence of gout attacks increases.

Kidney function and diuretics

Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (plasma creatinine in adults below 2.5 mg/dL or 220 µmol/L). At the beginning of diuretic treatment in patients, due to hypovolemia and hyponatremia, a temporary decrease in glomerular filtration rate and an increase in the concentration of urea and creatinine in the blood plasma may be observed. This transient functional renal failure is not dangerous for patients with unchanged renal function, but its severity may increase in patients with renal failure.

Photosensitivity

Cases of photosensitivity reactions have been reported while taking thiazide and thiazide-like diuretics. If photosensitivity reactions develop while taking the drug, treatment should be discontinued. If it is necessary to continue diuretic therapy, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays.

Athletes

Indapamide may give a positive reaction during doping control.

Impact on the ability to drive vehicles and operate machinery

The action of the substances included in the drug Noliprel® A does not lead to impairment of psychomotor reactions. However, some people may develop different individual reactions in response to lowering blood pressure, especially at the beginning of therapy or when other antihypertensive drugs are added to therapy. In this case, the ability to drive a car or operate other machinery may be reduced.

Pharmacokinetics and pharmacodynamics

The pharmacokinetics of perindopril and indapamide when used in combination is the same as when used separately. After oral administration, perindopril is rapidly absorbed. Bioavailability level - 65-70%. About 20% of total absorbed perindopril is later converted to perindoprilat (the active metabolite). The maximum concentration of perindoprilate in plasma is observed after 3-4 hours. Less than 30% binds to blood proteins, depending on the concentration in the blood plasma. The half-life is 25 hours. The substance penetrates the placental barrier. Perindoprilat is excreted from the body through the kidneys. Its half-life is 3-5 hours. There is a slower administration of perindoprilate in older people, as well as in patients with heart failure and renal failure.

Indapamide is completely and relatively quickly absorbed from the gastrointestinal tract. The maximum concentration of the substance in plasma is observed one hour after oral administration.

The substance binds to plasma proteins by 79%. Half-life is 19 hours. The substance is excreted in the form of inactive metabolites by the kidneys (approximately 70%) and intestines (approximately 22%). In people with renal failure, no changes in the pharmacokinetics of the substance are observed.

Noliprel A Bi-forte tablets 10 mg + 2.5 mg 30 pcs. in Moscow

Round, biconvex, white, film-coated tablets.

Noliprel® A Bi-forte

The combined use of perindopril and indapamide does not change their pharmacokinetic characteristics compared to the separate administration of these drugs.

Perindopril

When taken orally, perindopril is rapidly absorbed. Cmax in blood plasma is achieved 1 hour after oral administration. T1/2 is 1 hour. Perindopril has no pharmacological activity. Approximately 27% of the total amount of perindopril taken orally enters the bloodstream in the form of an active metabolite, perindoprilate. In addition to perindoprilate, 5 more metabolites are formed that do not have pharmacological activity. Cmax of perindoprilate in blood plasma is achieved 3–4 hours after oral administration of perindopril. Eating slows down the conversion of perindopril to perindoprilat, thereby affecting bioavailability. Therefore, the drug should be taken once a day, in the morning, before meals.

There is a linear relationship between the concentration of perindopril in the blood plasma and its dose. The Vd of unbound perindoprilate is approximately 0.2 l/kg. The association of perindoprilate with plasma proteins, mainly with ACE, depends on the concentration of perindopril and is about 20%.

Perindoprilat is excreted from the body by the kidneys. The effective T1/2 of the unbound fraction is about 17 hours, the equilibrium state is reached within 4 days.

The elimination of perindoprilate is slowed down in old age, as well as in patients with heart and renal failure.

The dialysis clearance of perindoprilate is 70 ml/min.

The pharmacokinetics of perindopril is changed in patients with liver cirrhosis: its hepatic clearance is reduced by 2 times. However, the amount of perindoprilate formed does not decrease, which does not require dose adjustment (see “Dosage and Administration” and “Special Instructions”).

Indapamide

Indapamide is quickly and completely absorbed from the gastrointestinal tract.

Cmax of indapamide in blood plasma is observed 1 hour after oral administration.

Connection with blood plasma proteins - 79%.

T1/2 is 14–24 hours (average 18 hours). Repeated administration of the drug does not lead to its accumulation in the body. It is excreted mainly by the kidneys (70% of the administered dose) and through the intestines (22%) in the form of inactive metabolites.

The pharmacokinetics of the drug does not change in patients with renal failure.

Noliprel® A Bi-forte is a combination drug containing perindopril arginine and indapamide. The pharmacological properties of the drug Noliprel® A Bi-forte combine the individual properties of each of the components.

1. Mechanism of action

Noliprel® A Bi-forte

The combination of perindopril arginine and indapamide enhances the effect of each of them.

Perindopril arginine

Perindopril is an inhibitor of the enzyme that converts angiotensin I to angiotensin II (ACE inhibitor). ACE, or kininase II, is an exopeptidase that carries out both the conversion of angiotensin I into the vasoconstrictor substance angiotensin II, and the destruction of bradykinin, which has a vasodilatory effect, into an inactive heptapeptide. As a result, perindopril:

- reduces the secretion of aldosterone;

- according to the principle of negative feedback, it increases the activity of renin in the blood plasma;

- with long-term use, it reduces the peripheral vascular resistance, which is mainly due to the effect on the vessels in the muscles and kidneys. These effects are not accompanied by salt and water retention or the development of reflex tachycardia.

Perindopril normalizes myocardial function, reducing preload and afterload.

When studying hemodynamic parameters in patients with chronic heart failure, the following was revealed:

- decrease in filling pressure in the left and right ventricles of the heart;

— decrease in OPSS;

- increased cardiac output and increased cardiac index;

- increased muscle peripheral blood flow.

Indapamide

Indapamide belongs to the group of sulfonamides; its pharmacological properties are similar to thiazide diuretics. Indapamide inhibits the reabsorption of sodium ions in the cortical segment of the loop of Henle, which leads to an increase in the excretion of sodium, chlorine and, to a lesser extent, potassium and magnesium ions by the kidneys, thereby increasing diuresis and reducing blood pressure.

2. Antihypertensive effect

Noliprel® A Bi-forte

Noliprel® A Bi-forte has a dose-dependent hypotensive effect on both DBP and SBP in the standing and lying position. The hypotensive effect of the drug persists for 24 hours. A stable therapeutic effect occurs less than 1 month from the start of therapy and is not accompanied by tachycardia. Stopping treatment does not cause withdrawal syndrome.

Noliprel® A Bi-forte reduces the degree of left ventricular hypertrophy, improves arterial elasticity, reduces peripheral vascular resistance, and does not affect lipid metabolism (total cholesterol, HDL and LDL cholesterol, triglycerides).

The effect of the drug on cardiovascular morbidity and mortality has not been studied.

A more pronounced effect of the combination of perindopril and indapamide on left ventricular hypertrophy (LVH) compared to enalapril has been proven. In patients with arterial hypertension and LVH who received therapy with perindopril terbutylamine at a dose of 2 mg (equivalent to 2.5 mg perindopril arginine)/indapamide at a dose of 0.625 mg or enalapril at a dose of 10 mg 1 time per day, and with an increase in the dose of perindopril to 8 mg (equivalent to 10 mg perindopril arginine) and indapamide up to 2.5 mg, or enalapril up to 40 mg once a day, a more significant decrease in left ventricular mass index (LVMI) was noted in the perindopril/indapamide group (−10.1 g/m2) according to compared with the enalapril group (−1.1 g/m2). The difference in the degree of reduction in this indicator between groups was −8.3 g/m2 (95% CI (−11.5, −5.0), p<0.0001). The most significant effect on LVMI is achieved with the use of perindopril terbutylamine at a dose of 8 mg and indapamide at a dose of 2.5 mg.

A more pronounced hypotensive effect was noted during combination therapy with perindopril and indapamide compared to enalapril. The difference in blood pressure reduction between groups was −5.8 mmHg. Art. (95% CI (−7.9, −3.7), p<0.0001) - for SBP and −2.3 mmHg. Art. (95% CI (−3.6, −0.9), p=0.0004) - for dBP ( PICXEL

).

Perindopril

Perindopril is effective in the treatment of arterial hypertension of any severity.

The hypotensive effect of the drug reaches its maximum 4–6 hours after a single oral dose and persists for 24 hours. 24 hours after taking the drug, a pronounced (about 80%) residual ACE inhibition is observed.

Perindopril has a hypotensive effect in patients with both low and normal renin activity in the blood plasma.

The simultaneous administration of thiazide diuretics increases the severity of the hypotensive effect. In addition, the combination of an ACE inhibitor and a thiazide diuretic also reduces the risk of hypokalemia while taking diuretics.

Indapamide

The hypotensive effect occurs when the drug is used in doses that have a minimal diuretic effect.

The hypotensive effect of indapamide is associated with an improvement in the elastic properties of large arteries and a decrease in peripheral vascular resistance.

Indapamide reduces LVOT.

Indapamide does not affect the concentration of lipids in the blood plasma: triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol; carbohydrate metabolism (including in patients with concomitant diabetes mellitus).

Noliprel® A Bi-forte

Lithium preparations

The simultaneous use of a combination of perindopril and indapamide with lithium preparations is not recommended (see "Interactions").

Renal dysfunction

Therapy with Noliprel® A Bi-forte is contraindicated in patients with moderate and severe renal failure (Cl creatinine <60 ml/min). Some patients with arterial hypertension, without previous obvious impairment of renal function during therapy, may develop laboratory signs of functional renal failure. In this case, treatment with Noliprel® A Bi-forte should be discontinued. In the future, you can resume combination therapy using low doses of a combination of perindopril and indapamide, or use the drugs in monotherapy.

Such patients require regular monitoring of the content of potassium ions and creatinine in the blood serum - 2 weeks after the start of therapy and then every 2 months. Renal failure occurs more often in patients with severe chronic heart failure or underlying renal impairment, incl. with renal artery stenosis.

Noliprel® A Bi-forte is not recommended for patients with bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney.

Arterial hypotension and water-electrolyte imbalance

Hyponatremia is associated with a risk of sudden development of arterial hypotension (especially in patients with renal artery stenosis, including bilateral). Therefore, when monitoring patients, attention should be paid to possible symptoms of dehydration and decreased plasma electrolytes, for example after diarrhea or vomiting. Such patients require regular monitoring of blood plasma electrolyte levels.

In case of severe arterial hypotension, intravenous administration of 0.9% sodium chloride solution may be required.

Transient arterial hypotension is not a contraindication for continued therapy. After restoration of blood volume and blood pressure, therapy can be resumed using low doses of a combination of perindopril and indapamide, or the drugs can be used as monotherapy.

Potassium content

The combined use of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal failure. As with the use of other antihypertensive drugs in combination with a diuretic, regular monitoring of the content of potassium ions in the blood plasma is necessary.

Excipients

It should be taken into account that the excipients of the drug include lactose monohydrate. Noliprel® A Bi-forte should not be prescribed to patients with hereditary galactose intolerance, lactase deficiency and glucose-galactose malabsorption.

Perindopril

Neutropenia/agranulocytosis

The risk of developing neutropenia while taking ACE inhibitors is dose-dependent and depends on the drug taken and the presence of concomitant diseases. Neutropenia rarely occurs in patients without concomitant diseases, but the risk increases in patients with impaired renal function, especially against the background of systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma).

After discontinuation of ACE inhibitors, clinical signs of neutropenia disappear on their own.

Perindopril should be used with extreme caution in patients with systemic connective tissue diseases, while taking immunosuppressive drugs, allopurinol or procainamide and when used together, especially in patients with underlying renal impairment. Some patients developed severe infectious diseases, in some cases resistant to intensive antibiotic therapy. When prescribing perindopril to such patients, it is recommended to periodically monitor the number of leukocytes in the blood. Patients should tell their doctor about any signs of infectious diseases (eg, sore throat, fever).

Hypersensitivity/angioedema (Quincke's edema)

When taking ACE inhibitors, incl. and perindopril, in rare cases, the development of angioedema of the face, extremities, lips, tongue, glottis and/or larynx may occur. If symptoms appear, taking Noliprel® A Bi-forte should be stopped immediately, and the patient should be observed until signs of edema disappear completely. If the swelling affects only the face and lips, it usually resolves on its own, although antihistamines may be used to treat symptoms.

Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, glottis, or larynx can lead to airway obstruction. If such symptoms appear, you should immediately administer epinephrine (adrenaline) subcutaneously at a dilution of 1:1000 (0.3 or 0.5 ml) and/or ensure airway patency.

Patients with a history of angioedema, not associated with taking ACE inhibitors, may have an increased risk of developing it when taking drugs of this group (see “Contraindications”).

In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. In this case, patients experience abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and with normal activity of the C1 esterase enzyme. The diagnosis is made using computed tomography of the abdominal region, ultrasound, or at the time of surgery. Symptoms disappear after stopping ACE inhibitors. In patients with abdominal pain receiving ACE inhibitors, the possibility of developing angioedema of the intestine must be taken into account when making a differential diagnosis.

Anaphylactoid reactions during desensitization

There are isolated reports of the development of long-term life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with the venom of hymenoptera insects (bees, wasps). ACE inhibitors should be used with caution in patients with a history of allergies or a tendency to allergic reactions undergoing desensitization procedures. Prescription of an ACE inhibitor should be avoided in patients receiving immunotherapy with hymenoptera venom. However, an anaphylactoid reaction can be avoided by temporarily discontinuing the ACE inhibitor at least 24 hours before the start of the desensitization procedure.

Anaphylactoid reactions during LDL apheresis

In rare cases, life-threatening anaphylactoid reactions may occur in patients receiving ACE inhibitors during LDL apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be temporarily discontinued before each apheresis procedure.

Hemodialysis

Anaphylactoid reactions have been reported in patients receiving ACE inhibitors during hemodialysis using high-flux membranes (eg AN69®). Therefore, it is advisable to use a different type of membrane or use an antihypertensive agent of a different pharmacotherapeutic group.

Potassium-sparing diuretics and potassium supplements

As a rule, the combined use of perindopril and potassium-sparing diuretics, as well as potassium preparations and potassium-containing table salt substitutes is not recommended (see “Interactions”).

Cough

During therapy with an ACE inhibitor, a dry cough may occur. The cough persists for a long time while taking drugs of this group and disappears after their discontinuation. If a patient develops a dry cough, one should be aware of the possible connection of this symptom with taking an ACE inhibitor. If the doctor believes that ACE inhibitor therapy is necessary for the patient, the drug may be continued.

Children and teenagers

Noliprel® A Bi-forte should not be prescribed to children and adolescents under the age of 18 years due to the lack of data on the effectiveness and safety of the use of single drugs or combination therapy in patients in this age group.

Risk of arterial hypotension and/or renal failure (in patients with chronic heart failure, fluid and electrolyte imbalance, etc.)

In some pathological conditions, significant activation of the RAAS may be observed, especially with severe hypovolemia and a decrease in the content of electrolytes in the blood plasma (against the background of a salt-free diet or long-term use of diuretics), in patients with initially low blood pressure, bilateral renal artery stenosis or stenosis of the artery of a single kidney, chronic cardiac liver failure or cirrhosis with edema and ascites.

The use of ACE inhibitors causes blockade of the RAAS and therefore may be accompanied by a sharp decrease in blood pressure and/or an increase in the concentration of creatinine in the blood plasma, indicating the development of functional renal failure. These phenomena are more often observed when taking the first dose of the drug or during the first two weeks of therapy. Sometimes these conditions develop acutely. In such cases, when resuming therapy, it is recommended to use a combination of perindopril and indapamide at a lower dose and then gradually increase the dose.

Elderly patients

Before starting to take Noliprel® A Bi-forte, it is necessary to evaluate the functional activity of the kidneys and the content of potassium ions in the blood plasma. At the beginning of therapy, the dose of the drug is selected taking into account the degree of reduction in blood pressure, especially in the case of a decrease in blood volume and loss of electrolytes. Such measures help to avoid a sharp decrease in blood pressure.

Atherosclerosis

The risk of arterial hypotension exists in all patients, however, special care should be taken when using the drug in patients with coronary artery disease and cerebrovascular insufficiency. In such patients, treatment should begin with a low dose combination of perindopril arginine and indapamide.

Patients with renovascular hypertension

The treatment method for renovascular hypertension is revascularization. However, the use of ACE inhibitors has a beneficial effect in patients both awaiting surgery and in cases where surgery is not possible.

In patients with diagnosed or suspected renal artery stenosis, treatment should be initiated with lower doses of the combination of perindopril and indapamide. Some patients may develop functional renal failure, which disappears when Noliprel® A Bi-forte is discontinued.

Other risk groups

In patients with chronic heart failure (functional class IV according to the NYHA

) and patients with type 1 diabetes (risk of spontaneous increase in potassium ions), treatment should begin with lower doses of the combination of perindopril and indapamide and under constant medical supervision.

Patients with arterial hypertension and coronary artery disease should not stop taking beta-blockers: the combination of perindopril and indapamide should be used in conjunction with beta-blockers.

Patients with diabetes mellitus

When prescribing Noliprel® A Bi-forte to patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, regular monitoring of plasma glucose concentrations is necessary during the first month of therapy.

Ethnic differences

Perindopril, like other ACE inhibitors, apparently has a less pronounced hypotensive effect in patients of the Negroid race compared to representatives of other races. Perhaps this difference is due to the fact that patients with arterial hypertension of the Negroid race more often have low renin activity.

Surgery/general anesthesia

The use of ACE inhibitors in patients undergoing surgery under general anesthesia can lead to a significant decrease in blood pressure, especially when using general anesthetic agents that have an antihypertensive effect.

It is recommended to stop taking long-acting ACE inhibitors, incl. perindopril, 12 hours before surgery.

Aortic stenosis/mitral stenosis/hypertrophic cardiomyopathy

ACE inhibitors should be prescribed with caution to patients with left ventricular outflow obstruction and mitral stenosis.

Liver failure

In rare cases, cholestatic jaundice occurs while taking ACE inhibitors. As this syndrome progresses, fulminant liver necrosis develops, sometimes with death. The mechanism of development of this syndrome is unclear. If jaundice occurs while taking ACE inhibitors, the patient should consult a doctor. If there is a significant increase in the activity of liver enzymes while taking ACE inhibitors, you should stop taking Noliprel® A Bi-forte (see “Side effects”).

Anemia

Anemia can develop in patients after kidney transplantation or in patients on hemodialysis. In this case, the decrease in hemoglobin is greater, the higher its initial value. This effect does not appear to be dose-dependent, but may be related to the mechanism of action of ACE inhibitors.

Hyperkalemia

Hyperkalemia may develop during treatment with ACE inhibitors, incl. and perindopril. Risk factors for hyperkalemia are renal failure, impaired renal function, old age, diabetes mellitus, certain concomitant conditions (dehydration, acute decompensation of chronic heart failure, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), and also potassium preparations or potassium-containing substitutes for table salt, as well as the use of other drugs that increase the content of potassium ions in the blood plasma (for example, heparin) (especially in patients with reduced renal function). Hyperkalemia can lead to serious, sometimes fatal, heart rhythm disturbances. If combined use of the above drugs is necessary, treatment should be carried out with caution, against the background of regular monitoring of the content of potassium ions in the blood serum (see “Interaction”).

Indapamide

In the presence of liver dysfunction, taking thiazide and thiazide-like diuretics can lead to the development of hepatic encephalopathy. In this case, you should immediately stop taking Noliprel® A Bi-forte.

Photosensitivity

Cases of photosensitivity reactions have been reported while taking thiazide and thiazide-like diuretics (see “Side effects”). If a photosensitivity reaction develops while taking the drug, treatment should be discontinued. If it is necessary to continue diuretic therapy, it is recommended to protect the skin from exposure to sunlight or artificial UV rays.

Water and electrolyte balance

Content of sodium ions in blood plasma.

Before starting treatment, it is necessary to determine the content of sodium ions in the blood plasma. While taking the drug, this indicator should be regularly monitored. All diuretics can cause hyponatremia, which sometimes leads to serious complications. Hyponatremia at the initial stage may not be accompanied by clinical symptoms, so regular laboratory monitoring is necessary. More frequent monitoring of sodium ion levels is indicated in elderly patients (see “Side effects” and “Overdose”).

Content of potassium ions in blood plasma.

Therapy with thiazide and thiazide-like diuretics is associated with a risk of hypokalemia. Hypokalemia (less than 3.4 mmol/l) should be avoided in the following categories of high-risk patients: elderly patients, debilitated patients or those receiving concomitant drug therapy, patients with liver cirrhosis, peripheral edema or ascites, coronary artery disease, chronic heart failure. Hypokalemia in these patients enhances the toxic effect of cardiac glycosides and increases the risk of developing arrhythmia.

The high-risk group also includes patients with an increased QT interval, and it does not matter whether this increase is caused by congenital causes or the effect of drugs.

Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, especially arrhythmias, which can be fatal. In all the cases described above, regular monitoring of the content of potassium ions in the blood plasma is necessary. The first measurement of potassium ion content should be carried out within the first week from the start of therapy.

If hypokalemia is detected, appropriate treatment should be prescribed.

Content of calcium ions in blood plasma.

Thiazide and thiazide-like diuretics reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in the content of calcium ions in the blood plasma. Severe hypercalcemia may be a consequence of previously undiagnosed hyperparathyroidism. Before studying the function of the parathyroid glands, you should stop taking diuretics.

Plasma glucose concentration

It is necessary to monitor blood glucose concentrations in patients with diabetes mellitus, especially in the presence of hypokalemia.

Uric acid

In patients with elevated concentrations of uric acid in the blood plasma, the frequency of gout attacks may increase during therapy.

Diuretics and kidney function

Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (plasma creatinine concentration in adult patients below 25 mg/l or 220 µmol/l). In elderly patients, creatinine Cl is calculated taking into account age, body weight and gender.

At the beginning of treatment with diuretics, patients due to hypovolemia and hyponatremia may experience a temporary decrease in glomerular filtration rate and an increase in the concentration of urea and creatinine in the blood plasma. This transient functional renal failure is not dangerous for patients with unchanged renal function, but its severity may increase in patients with renal failure.

Athletes

Indapamide may give a positive reaction during doping control.

Impact on the ability to drive a car or perform work that requires increased speed of physical and mental reactions.

The action of the agents included in the drug Noliprel® A Bi-forte does not lead to impairment of psychomotor reactions. However, some patients may develop different individual reactions in response to a decrease in blood pressure, especially at the beginning of therapy or when other antihypertensive drugs are added to the therapy. In this case, the ability to drive vehicles or perform work that requires increased speed of physical and mental reactions may be reduced.

Contraindications

Contraindications to the use of all types of the drug Noliprel are the following diseases and conditions:

• high sensitivity to the components of the drug or the presence of allergic reactions to its components;
• renal failure , in which creatinine clearance is less than 30 ml/min;
• liver failure , in which there is a tendency to encephalopathy ;
• combination with drugs that prolong the QT interval, as well as antiarrhythmic drugs;
• hypokalemia;
• renal artery stenosis;
• lactase deficiency, glucose-galactose malabsorption syndrome, galactosemia;
• history of angioedema;
• pregnancy , lactation ;
• age up to eighteen years.

Also, you should not take the drug at the same time as potassium supplements or potassium-sparing diuretics if the patient has hyperkalemia.

Due to the lack of sufficient information, it is not recommended to use the tablets for treatment in people who are on hemodialysis , as well as in patients with decompensated heart failure.

It is prescribed with caution to people with systemic connective tissue diseases, those taking antidepressants, and suppression of bone marrow hematopoiesis. angina pectoris are also treated with caution .

NOLIPREL A

special instructions

Noliprel® A
The use of Noliprel® A 2.5 mg + 0.625 mg, containing a low dose of indapamide and perindopril arginine, is not accompanied by a significant reduction in the incidence of side effects, with the exception of hypokalemia, compared with perindopril and indapamide at the lowest approved doses (see section "Side effects"). When initiating therapy with two antihypertensive drugs that the patient has not previously received, an increased risk of idiosyncrasy cannot be excluded. Careful monitoring of the patient can minimize this risk.

Renal dysfunction

Therapy is contraindicated in patients with severe renal failure (creatinine clearance less than 30 ml/min). In some patients with arterial hypertension without previous obvious renal impairment, laboratory signs of functional renal failure may appear during therapy. In this case, treatment should be stopped. In the future, you can resume combination therapy using low doses of drugs, or use drugs in monotherapy.

Such patients require regular monitoring of potassium and creatinine levels in the blood serum - 2 weeks after the start of therapy and every 2 months thereafter. Renal failure occurs more often in patients with severe chronic heart failure or underlying renal impairment, including renal artery stenosis.

Arterial hypotension and water-electrolyte imbalance

Hyponatremia is associated with a risk of sudden development of arterial hypotension (especially in patients with arterial stenosis of a solitary kidney and bilateral renal artery stenosis). Therefore, during dynamic monitoring of patients, attention should be paid to possible symptoms of dehydration and decreased levels of electrolytes in the blood plasma, for example, after diarrhea or vomiting. Such patients require regular monitoring of plasma electrolyte levels.

In case of severe arterial hypotension, intravenous administration of 0.9% sodium chloride solution may be required.

Transient arterial hypotension is not a contraindication for continued therapy. After restoration of circulating blood volume and blood pressure, therapy can be resumed using low doses of drugs, or drugs can be used as monotherapy.

Potassium level

The combined use of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal failure. As in the case of the combined use of antihypertensive drugs and a diuretic, regular monitoring of the level of potassium in the blood plasma is necessary.

Excipients

It should be taken into account that the excipients of the drug include lactose monohydrate. Noliprel® A should not be prescribed to patients with hereditary galactose intolerance, lactase deficiency and glucose-galactose malabsorption.

Lithium preparations

The simultaneous use of a combination of perindopril and indapamide with lithium preparations is not recommended (see section “Contraindications”, “Interaction with other drugs”).

Perindopril

Neutropenia/agranulocytosis

The risk of developing neutropenia while taking ACE inhibitors is dose-dependent and depends on the drug taken and the presence of concomitant diseases. Neutropenia rarely occurs in patients without concomitant diseases, but the risk increases in patients with impaired renal function, especially against the background of systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma). After discontinuation of ACE inhibitors, signs of neutropenia disappear on their own.

To avoid the development of such reactions, it is recommended to strictly follow the recommended dose. When prescribing ACE inhibitors to this group of patients, the benefit/risk factor should be carefully weighed.

Angioedema (Quincke's edema)

When taking ACE inhibitors, including perindopril, in rare cases, the development of angioedema of the face, extremities, lips, tongue, glottis and/or larynx may occur. If symptoms appear, perindopril should be discontinued immediately and the patient should be observed until signs of edema completely disappear. If the swelling affects only the face and lips, it usually resolves on its own, although antihistamines may be used to treat symptoms.

Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, glottis, or larynx can lead to airway obstruction. If such symptoms appear, you should immediately administer epinephrine (adrenaline) subcutaneously at a dilution of 1:1000 (0.3 or 0.5 ml) and/or ensure airway patency.

Patients with a history of angioedema not associated with taking ACE inhibitors may have an increased risk of developing it when taking drugs of this group (see section “Contraindications”).

In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors.

Anaphylactoid reactions during desensitization

There are isolated reports of the development of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with the venom of hymenoptera insects (bees, wasps). ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. Prescription of an ACE inhibitor should be avoided in patients receiving immunotherapy with hymenoptera venom. However, an anaphylactoid reaction can be avoided by temporarily discontinuing the ACE inhibitor at least 24 hours before the procedure.

Anaphylactoid reactions during LDL apheresis

In rare cases, life-threatening anaphylactoid reactions may occur in patients receiving ACE inhibitors, low-density lipoprotein (LDL) apheresis using dextran sulfate, or hemodialysis using high-flux membranes. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be temporarily discontinued at least 24 hours before the apheresis procedure.  

Cough

During therapy with an ACE inhibitor, a dry cough may occur. The cough persists for a long time while taking drugs of this group and disappears after their discontinuation. If a patient develops a dry cough, one should be aware of the possible iatrogenic nature of this symptom. If the attending physician believes that ACE inhibitor therapy is necessary for the patient, the drug may be continued.

Children and teenagers

The drug should not be prescribed to children and adolescents under the age of 18 years due to the lack of data on the effectiveness and safety of the use of perindopril as monotherapy or as part of combination therapy in patients in this age group.

Risk of arterial hypotension and/or renal failure (in patients with heart failure, fluid and electrolyte imbalance, etc.

)

In some pathological conditions, significant activation of the renin-angiotensin-aldosterone system may be observed, especially with severe hypovolemia and a decrease in the level of plasma electrolytes (due to a salt-free diet or long-term use of diuretics), in patients with initially low blood pressure, with bilateral renal artery stenosis or with stenosis of the artery of a single kidney, chronic heart failure or cirrhosis of the liver with edema and ascites. The use of an ACE inhibitor causes a blockade of this system and therefore may be accompanied by a sharp decrease in blood pressure and/or an increase in plasma creatinine levels, indicating the development of functional renal failure. These phenomena are more often observed when taking the first dose of the drug or during the first two weeks of therapy. Sometimes these conditions develop acutely and during other periods of therapy. In such cases, when resuming therapy, it is recommended to use the drug at a lower dose and then gradually increase the dose.

Elderly patients

Before starting to take the drug, it is necessary to assess the functional activity of the kidneys and the concentration of potassium in the blood plasma. At the beginning of therapy, the dose of the drug is selected taking into account the degree of reduction in blood pressure, especially in the case of dehydration and loss of electrolytes. Such measures help to avoid a sharp decrease in blood pressure.

Atherosclerosis

The risk of arterial hypotension exists in all patients, however, special care should be taken when using the drug in patients with coronary heart disease and cerebrovascular insufficiency. In such patients, treatment should be started with low doses.

Patients with renovascular hypertension

The treatment method for renovascular hypertension is revascularization. However, the use of ACE inhibitors has a beneficial effect in this category of patients, both awaiting surgery and in cases where surgery is not possible.

Treatment with Noliprel® A in patients with diagnosed or suspected bilateral renal artery stenosis or stenosis of the artery of a single kidney should begin with a low dose of the drug in a hospital setting, monitoring renal function and potassium concentration in the blood plasma. Some patients may develop functional renal failure, which disappears when the drug is discontinued.

Other risk groups

In persons with severe heart failure (stage IV) and patients with insulin-dependent diabetes mellitus (risk of spontaneous increase in potassium concentration), treatment should begin with a low dose of the drug and under constant medical supervision.

Hypertensive patients with coronary artery disease should not stop taking beta-blockers: ACE inhibitors should be used together with beta-blockers.

Anemia

Anemia can develop in patients after kidney transplantation or in people on hemodialysis. In this case, the decrease in hemoglobin concentration is greater, the higher its initial value. This effect does not appear to be dose-dependent, but may be related to the mechanism of action of ACE inhibitors.  

A slight decrease in hemoglobin concentration occurs during the first 6 months, then it remains stable and is completely restored after discontinuation of the drug. In such patients, treatment can be continued, but hematological tests should be performed regularly.

Surgery / General anesthesia

The use of ACE inhibitors in patients undergoing surgery under general anesthesia can lead to a significant decrease in blood pressure, especially when using general anesthesia agents that have a hypotensive effect.

It is recommended to stop taking long-acting ACE inhibitors, including perindopril, the day before surgery. It is necessary to warn the anesthesiologist that the patient is taking ACE inhibitors.

Aortic stenosis / Hypertrophic cardiomyopathy

ACE inhibitors should be prescribed with caution to patients with left ventricular outflow tract obstruction.

Liver failure

In rare cases, cholestatic jaundice occurs while taking ACE inhibitors. As this syndrome progresses, liver necrosis may rapidly develop, sometimes with death. The mechanism of development of this syndrome is unclear. If jaundice appears or a significant increase in the activity of liver enzymes while taking ACE inhibitors, you should stop taking the drug and consult a doctor (see section “Side Effects”).

Indapamide

In the presence of liver dysfunction, taking thiazide and thiazide-like diuretics can lead to the development of hepatic encephalopathy. In this case, you should immediately stop taking the drug.

Water and electrolyte balance

Sodium content in blood plasma

Before starting treatment, it is necessary to determine the content of sodium ions in the blood plasma. While taking the drug, this indicator should be regularly monitored. All diuretics can cause hyponatremia, which sometimes leads to serious complications. Hyponatremia at the initial stage may not be accompanied by clinical symptoms, so regular laboratory monitoring is necessary. More frequent monitoring of sodium ion levels is indicated for patients with liver cirrhosis and the elderly (see section “Side effects” and “Overdose”).

Content of potassium ions in blood plasma

Therapy with thiazide and thiazide-like diuretics is associated with a risk of hypokalemia. Hypokalemia (less than 3.4 mmol/l) should be avoided in the following categories of high-risk patients: elderly patients, debilitated patients or those receiving concomitant drug therapy, patients with liver cirrhosis, peripheral edema or ascites, coronary artery disease, heart failure. Hypokalemia in these patients enhances the toxic effect of cardiac glycosides and increases the risk of developing arrhythmias.

The high-risk group also includes patients with an increased QT interval, and it does not matter whether this increase is caused by congenital causes or the effect of drugs.

Hypokalemia, like bradycardia, contributes to the development of severe heart rhythm disturbances, especially arrhythmias, which can be fatal. In all the cases described above, more regular monitoring of the content of potassium ions in the blood plasma is necessary. The first measurement of potassium ion concentration should be carried out within the first week from the start of therapy.

If hypokalemia is detected, appropriate treatment should be prescribed.

Content of calcium ions in blood plasma

Thiazide and thiazide-like diuretics reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in the concentration of calcium in the blood plasma. Severe hypercalcemia may be a consequence of previously undiagnosed hyperparathyroidism. Before studying the function of the parathyroid gland, you should stop taking diuretics.

Plasma glucose levels

It is necessary to monitor blood glucose levels in patients with diabetes mellitus, especially in the presence of hypokalemia.

Uric acid

In patients with elevated levels of uric acid in the blood plasma during therapy, the frequency of gout attacks may increase.

Diuretics and kidney function

Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (plasma creatinine in adults below 25 mg/l or 220 µmol/l).

At the beginning of diuretic treatment in patients, due to hypovolemia and hyponatremia, a temporary decrease in glomerular filtration rate and an increase in the concentration of urea and creatinine in the blood plasma may be observed. This transient functional renal failure is not dangerous for patients with unchanged renal function, but its severity may increase in patients with renal failure.

Photosensitivity

Cases of photosensitivity reactions have been reported while taking thiazide and thiazide-like diuretics. If photosensitivity reactions develop while taking the drug, treatment should be discontinued. If it is necessary to continue diuretic therapy, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays.

Athletes

Indapamide may give a positive reaction during doping control.

Side effects

• In the functions of the cardiovascular system : severe hypotension, orthostatic collapse, in rare cases: arrhythmia , stroke , myocardial infarction .
• In the functions of the genitourinary system : deterioration of kidney function, proteinuria in people with glomerular nephropathy, in rare cases - acute renal failure. There may be a decrease in potency.
• In the functions of the central and peripheral nervous system : severe fatigue, dizziness , headache , asthenia, unstable mood, impaired hearing, vision, decreased appetite, convulsions, and in some cases, stupor.
• In the functions of the respiratory system : cough, difficulty breathing, bronchospasm, nasal discharge.
• In the functions of the gastrointestinal tract : dyspepsia, abdominal pain, pancreatitis , cholestasis, increased transaminase activity, hyperbilirubinemia.
• In the functions of the blood system : against the background of hemodialysis or after a kidney transplant, patients may develop anemia, in rare cases - thrombocytopenia, pancytopenia, agranulocytosis, hemolytic anemia.
• Allergic manifestations : skin itching, rash, swelling, urticaria.
• Patients with liver failure may develop hepatic encephalopathy. People with impaired water-electrolyte balance may experience hyponatremia, hypovolemia, hypokalemia, and dehydration.

Noliprel A forte tablets 1.25 mg+5 mg 30 pcs.

From the circulatory and lymphatic system. Very rare: thrombocytopenia, leukopenia/neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia. Anemia: In certain clinical situations (kidney transplant patients, hemodialysis patients), ACE inhibitors may cause anemia. From the central nervous system. Common: paresthesia, headache, dizziness, asthenia, vertigo. Uncommon: sleep disturbance, mood lability. Very rare: confusion. Unspecified frequency: fainting. From the side of the organ of vision. Common: blurred vision. From the side of the hearing organ. Common: tinnitus. From the cardiovascular system. Often: marked decrease in blood pressure, including orthostatic hypotension. Very rare: cardiac arrhythmias, including bradycardia, ventricular tachycardia, atrial fibrillation, as well as angina pectoris and myocardial infarction, possibly due to an excessive decrease in blood pressure in high-risk patients. Unspecified frequency: ari (possibly fatal). From the respiratory system, chest organs and mediastinum. Often: while using ACE inhibitors, a dry cough may occur, which persists for a long time while taking drugs of this group and disappears after their discontinuation. Dyspnea. Uncommon: bronchospasm. Very rare: eosinophilic pneumonia, rhinitis. From the digestive system. Often: dryness of the oral mucosa, nausea, vomiting, abdominal pain, epigastric pain, impaired taste perception, decreased appetite, dyspepsia, constipation, diarrhea. Very rare: angioedema of the intestine, cholestatic jaundice, pancreatitis. Unspecified frequency: hepatic encephalopathy in patients with liver failure, hepatitis. From the skin and subcutaneous fat. Common: skin rash, pruritus, maculopapular rash. Uncommon: angioedema of the face, lips, extremities, mucous membrane of the tongue, vocal folds and/or larynx; hives; hypersensitivity reactions in patients predisposed to broncho-obstructive and allergic reactions; purpura. In patients with acute form of systemic lupus erythematosus, the course of the disease may worsen. Very rare: erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome. Cases of photosensitivity reactions have been reported. From the musculoskeletal system and connective tissue. Common: muscle spasms. From the urinary system. Uncommon: renal failure. Very rare: acute renal failure. From the reproductive system. Uncommon: impotence. General disorders and symptoms. Often: asthenia. Uncommon: increased sweating.

Instructions for use of Noliprel (Method and dosage)

It is advisable to take Noliprel tablets in the morning. The medicine is prescribed one tablet per day. The instructions for Noliprel Forte provide for a similar treatment regimen. Noliprel A and Noliprel A Bi Forte are prescribed to patients 1 tablet per day. If patients have creatinine clearance equal to or greater than 30 ml/min, then there is no need to reduce the dose. If clearance equals or exceeds 60 ml per day, then during treatment it is necessary to carefully monitor the level of potassium and creatinine in the blood.

If necessary, after several months of treatment, the doctor may increase the dose by prescribing Noliprel A Forte or another type of this drug instead of Noliprel.

Noliprel®

Perindopril, indapamide

The use of Noliprel® is not accompanied by a significant reduction in the frequency of side effects, with the exception of hypokalemia, compared with perindopril and indapamide in the lowest approved doses (see section “Side Effects”). When initiating therapy with two antihypertensive drugs that the patient has not previously received, an increased risk of idiosyncrasy cannot be excluded. Careful monitoring of the patient can minimize this risk.

Lithium preparations

The simultaneous use of a combination of perindopril and indapamide with lithium preparations is not recommended (see section “Interaction with other drugs”).

Renal dysfunction

Therapy is contraindicated in patients with severe renal failure (creatinine clearance less than 30 ml/min). In some patients with hypertension without previous obvious renal impairment, laboratory signs of functional renal failure may appear during therapy. In this case, treatment should be stopped. In the future, you can resume combination therapy using low doses of drugs, or use drugs in monotherapy.

Such patients require regular monitoring of serum potassium and creatinine levels - 2 weeks after the start of therapy and every 2 months thereafter. Renal failure occurs more often in patients with severe heart failure or underlying renal impairment, including stenosis of one or two renal arteries.

As a rule, the use of perindopril and indapamide is not recommended for patients with bilateral renal artery stenosis or stenosis of a single functioning kidney.

Arterial hypotension and water-electrolyte imbalance

Hyponatremia is associated with a risk of sudden development of arterial hypotension (especially in patients with stenosis of one or two renal arteries). Therefore, during dynamic monitoring of patients, attention should be paid to possible symptoms of dehydration and decreased levels of electrolytes in the blood plasma, for example, after diarrhea or vomiting. Such patients require regular monitoring of plasma electrolyte levels.

In case of severe arterial hypotension, intravenous administration of 0.9% sodium chloride solution may be required.

Transient arterial hypotension is not a contraindication for continued therapy. After restoration of circulating blood volume and blood pressure, therapy can be resumed using low doses of drugs, or drugs can be used as monotherapy.

Potassium level

The combined use of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal failure. As in the case of the combined use of antihypertensive drugs and a diuretic, regular monitoring of the level of potassium in the blood plasma is necessary.

Excipients

It should be taken into account that the excipients of the drug include lactose monohydrate. Noliprel® should not be prescribed to patients with hereditary galactose intolerance, lactase deficiency and glucose-galactose malabsorption.

Perindopril

Neutropenia/agranulocytosis

The risk of developing neutropenia while taking ACE inhibitors is dose-dependent and depends on the drug taken and the presence of concomitant diseases. Neutropenia rarely occurs in patients without concomitant diseases, but the risk increases in patients with impaired renal function, especially against the background of systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma).

After discontinuation of ACE inhibitors, signs of neutropenia disappear on their own.

Perindopril should be used with extreme caution in patients with diffuse connective tissue diseases, while taking immunosuppressive drugs, allopurinol or procainamide, and with simultaneous exposure to these factors, especially in patients with underlying renal impairment. Some patients developed severe infections, in some cases resistant to intensive antibiotic therapy. When prescribing perindopril to such patients, it is recommended to periodically monitor the number of leukocytes in the blood. Patients should report any signs of infectious diseases (eg, sore throat, fever) to their doctor.

Hypersensitivity/angioedema (Quincke's edema)

When taking ACE inhibitors, including perindopril, in rare cases, the development of angioedema of the face, extremities, lips, tongue, glottis and/or larynx may occur. If symptoms appear, perindopril should be discontinued immediately and the patient should be observed until signs of edema completely disappear. If the swelling affects only the face and lips, it usually resolves on its own, although antihistamines may be used to treat symptoms.

Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, glottis, or larynx can lead to airway obstruction. If such symptoms appear, you should immediately administer epinephrine (adrenaline) subcutaneously at a dilution of 1:1000 (0.3 or 0.5 ml) and/or ensure airway patency.

Patients with a history of angioedema, not associated with taking ACE inhibitors, may have an increased risk of developing it when taking drugs of this group (see section "Contraindications").

In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. In this case, patients experience abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and with normal levels of C-1 esterase. The diagnosis is made using computed tomography of the abdominal region, ultrasound, or at the time of surgery. Symptoms disappear after stopping ACE inhibitors. In patients with abdominal pain receiving ACE inhibitors, the possibility of developing angioedema of the intestine must be taken into account when making a differential diagnosis.

Anaphylactoid reactions during desensitization

There are isolated reports of the development of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with the venom of hymenoptera insects (bees, wasps). ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. Prescription of an ACE inhibitor should be avoided in patients receiving immunotherapy with hymenoptera venom. However, an anaphylactoid reaction can be avoided by temporarily discontinuing the ACE inhibitor at least 24 hours before the procedure.

Anaphylactoid reactions during LDL apheresis

In rare cases, life-threatening anaphylactoid reactions may occur in patients receiving ACE inhibitors during low-density lipoprotein (LDL) apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be temporarily discontinued before each apheresis procedure.

Hemodialysis

Anaphylactoid reactions have been reported in patients receiving ACE inhibitors during hemodialysis using high-flux membranes (eg, AN69®). Therefore, it is advisable to use a different type of membrane or use an antihypertensive drug of a different pharmacotherapeutic group.

Potassium-sparing diuretics and potassium supplements

As a rule, the combined use of perindopril and potassium-sparing diuretics, as well as potassium preparations and potassium-containing table salt substitutes is not recommended (see section “Interaction with other drugs”).

Cough

During therapy with an ACE inhibitor, a dry cough may occur. The cough persists for a long time while taking drugs of this group and disappears after their discontinuation. If a patient develops a dry cough, one should be aware of the possible connection of this symptom with taking an ACE inhibitor. If the attending physician believes that ACE inhibitor therapy is necessary for the patient, the drug may be continued.

Children and teenagers

Noliprel® should not be prescribed to children and adolescents under the age of 18 years due to the lack of data on the effectiveness and safety of the use of perindopril as monotherapy or as part of combination therapy in patients in this age group.

Risk of arterial hypotension and/or renal failure (in patients with heart failure, fluid and electrolyte imbalance, etc.)

In some pathological conditions, significant activation of the renin-angiotensin-aldosterone system may be observed, especially with severe hypovolemia and a decrease in the level of plasma electrolytes (against the background of a salt-free diet or long-term use of diuretics), in patients with initially low blood pressure, stenosis of one or two kidneys arteries, chronic heart failure or cirrhosis of the liver with the presence of edema and ascites.

The use of an ACE inhibitor causes a blockade of this system and therefore may be accompanied by a sharp decrease in blood pressure and/or an increase in plasma creatinine levels, indicating the development of functional renal failure. These phenomena are more often observed when taking the first dose of the drug or during the first two weeks of therapy. Sometimes these conditions develop acutely and during other periods of therapy. In such cases, when resuming therapy, it is recommended to use the drug at a lower dose and then gradually increase the dose.

Elderly patients

Before starting to take the drug, it is necessary to assess the functional activity of the kidneys and the concentration of potassium in the blood plasma. At the beginning of therapy, the dose of the drug is selected taking into account the degree of reduction in blood pressure, especially in the case of dehydration and loss of electrolytes. Such measures help to avoid a sharp decrease in blood pressure.

Atherosclerosis

The risk of arterial hypotension exists in all patients, however, special care should be taken when using the drug in patients with coronary heart disease and cerebrovascular insufficiency. In such patients, treatment should be started with low doses.

Patients with renovascular hypertension

The treatment method for renovascular hypertension is revascularization. However, the use of ACE inhibitors has a beneficial effect in patients both awaiting surgery and in cases where such surgery cannot be performed.

Treatment with Noliprel® in patients with diagnosed or suspected renal artery stenosis should begin with a low dose of the drug in a hospital setting, monitoring renal function and potassium concentration in the blood plasma. Some patients may develop functional renal failure, which disappears when the drug is discontinued.

Other risk groups

In persons with chronic heart failure (stage IV) and patients with insulin-dependent diabetes mellitus (risk of spontaneous increase in potassium concentration), treatment should begin with a low dose of the drug (half a tablet) and under constant medical supervision.

Patients with arterial hypertension and coronary heart disease should not stop taking beta-blockers: ACE inhibitors should be used together with beta-blockers.

Patients with diabetes mellitus

When prescribing the drug to patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, blood glucose levels should be carefully monitored during the first month of therapy.

Ethnic differences

Perindopril, like other ACE inhibitors, apparently has a less pronounced hypotensive effect in patients of the Negroid race compared to representatives of other races. Perhaps this difference is due to the fact that patients with arterial hypertension of the Negroid race more often have low renin activity.

Surgery/General anesthesia

The use of ACE inhibitors in patients undergoing surgery under general anesthesia can lead to a significant decrease in blood pressure, especially when using general anesthesia agents that have a hypotensive effect.

It is recommended to stop taking long-acting ACE inhibitors, including perindopril, 12 hours before surgery.

Aortic stenosis / Mitral stenosis / Hypertrophic cardiomyopathy

ACE inhibitors should be prescribed with caution to patients with left ventricular outflow tract obstruction.

Liver failure

In rare cases, it occurs while taking ACE inhibitors. cholestatic jaundice. As this syndrome progresses, fulminant liver necrosis develops, sometimes with death. The mechanism of development of this syndrome is unclear. If jaundice or a significant increase in the activity of liver enzymes occurs while taking ACE inhibitors, you should stop taking the drug and consult a doctor (see section “Side Effects”).

Anemia

Anemia can develop in patients after kidney transplantation or in people on hemodialysis. In this case, the decrease in hemoglobin concentration is greater, the higher its initial value. This effect does not appear to be dose-dependent, but may be related to the mechanism of action of ACE inhibitors.

Hyperkalemia

Hyperkalemia may develop during treatment with ACE inhibitors, including perindopril. Risk factors for hyperkalemia include renal failure, decreased renal function, advanced age, diabetes mellitus, certain concomitant conditions (dehydration, acute decompensated heart failure, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), and potassium preparations or potassium-containing substitutes for table salt, as well as the use of other drugs that increase the level of potassium in the blood plasma (for example, heparin). The use of potassium supplements, potassium-sparing diuretics, and potassium-containing table salt substitutes can lead to a significant increase in potassium levels in the blood, especially in patients with reduced renal function. Hyperkalemia can cause serious, sometimes fatal, abnormal heart rhythms. If combined use of the above drugs is necessary, treatment should be carried out with caution, against the background of regular monitoring of potassium levels in the blood serum (see section “Interaction with other drugs”).

Indapamide

When thiazide and thiazide-like diuretics are prescribed to patients with impaired liver function, hepatic encephalopathy may develop. In this case, diuretics should be stopped immediately.

Photosensitivity

While taking thiazide and thiazide-like diuretics, cases of photosensitivity reactions have been reported (see section "Side effects"). If photosensitivity reactions develop while taking the drug, treatment should be discontinued. If it is necessary to continue diuretic therapy, it is recommended to protect the skin from exposure to sunlight or artificial UV rays.

Water and electrolyte balance

Content of sodium ions in blood plasma

Before starting treatment, it is necessary to determine the content of sodium ions in the blood plasma. While taking the drug, this indicator should be regularly monitored. All diuretics can cause hyponatremia, which sometimes leads to serious complications. Hyponatremia at the initial stage may not be accompanied by clinical symptoms, so regular laboratory monitoring is necessary. More frequent monitoring of sodium ion levels is indicated for patients with liver cirrhosis and the elderly (see sections “Side effects” and “Overdose”).

Content of potassium ions in blood plasma

Therapy with thiazide and thiazide-like diuretics is associated with a risk of hypokalemia. Hypokalemia (less than 3.4 mmol/l) should be avoided in the following high-risk patients: elderly patients, debilitated patients or those receiving concomitant drug therapy, patients with liver cirrhosis, peripheral edema or ascites, coronary artery disease, heart failure. Hypokalemia in these patients enhances the toxic effect of cardiac glycosides and increases the risk of developing arrhythmias.

Patients with an increased QT interval are also at increased risk, and it does not matter whether this increase is caused by congenital causes or the effect of drugs.

Hypokalemia, like bradycardia, contributes to the development of severe heart rhythm disturbances, especially arrhythmias, which can be fatal. In all the cases described above, more regular monitoring of the content of potassium ions in the blood plasma is necessary. The first measurement of potassium ion concentration should be carried out within the first week from the start of therapy.

If hypokalemia is detected, appropriate treatment should be prescribed.

Content of calcium ions in blood plasma

Thiazide and thiazide-like diuretics reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in the concentration of calcium in the blood plasma. Severe hypercalcemia may be a consequence of previously undiagnosed hyperparathyroidism. Before studying the function of the parathyroid gland, you should stop taking diuretic drugs.

Plasma glucose levels

It is necessary to monitor blood glucose levels in patients with diabetes mellitus, especially in the presence of hypokalemia.

Uric acid

In patients with elevated levels of uric acid in the blood plasma during therapy, the frequency of gout attacks may increase.

Diuretics and kidney function

Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (plasma creatinine in adults below 25 mg/l or 220 µmol/l). In elderly patients, creatinine clearance is calculated taking into account age, body weight and gender.

At the beginning of treatment with diuretics, patients due to hypovolemia and hyponatremia may experience a temporary decrease in glomerular filtration rate and an increase in the concentration of urea and creatinine in the blood plasma. This transient functional renal failure is not dangerous for patients with unchanged renal function, but its severity may increase in patients with renal failure.

Athletes

Indapamide may give a positive reaction during doping control.

Overdose

In case of an overdose of the drug, there is a severe decrease in blood pressure, nausea, vomiting, dizziness , mood instability, symptoms of renal failure, and electrolyte imbalance. In this case, you need to immediately bring the water-electrolyte balance back to normal, rinse the stomach, and take enterosorbents. Noliprel metabolites can be removed using dialysis. If necessary, intravenous saline is administered.

Interaction

Noliprel should not be taken at the same time as lithium medications. If it is impossible to discontinue one of the drugs, the lithium level in the blood should be closely monitored.

With simultaneous treatment with potassium-sparing diuretics or drugs with potassium, the concentration of potassium in the blood may increase. This combination is recommended only for hypokalemia.

When indapamide with vincamine, bepridil, sultopride, halofantrine, as well as with simultaneous intravenous administration of erythromycin , arrhythmia and bradycardia may occur.

Sometimes, with simultaneous treatment with Insulin and Noliprel, hypoglycemia may develop.

When taking non-steroidal anti-inflammatory drugs, the antihypertensive properties of Noliprel are inhibited. If you are dehydrated, this combination of medications can cause kidney problems or kidney failure.

When treated with Noliprel and antipsychotics or tricyclic antidepressants, orthostatic hypotension may develop.

Due to the retention of water and electrolytes in the body, with simultaneous treatment with Noliprel and mineralocorticoids, glucocorticosteroids, stimulant laxatives, tetracosactide, amphotericin B, the hypotensive effect is reduced and the likelihood of hypokalemia increases.

Due to the possibility of developing hypokalemia, the risk of toxic effects of cardiac glycosides increases.

When combined with Metformin, acidosis may develop .

Before using iodine-containing X-ray contrast agents with Noliprel, the body must be adequately hydrated.

The simultaneous use of calcium salts can provoke hypercalcemia.

Concomitant treatment with cyclosporine may increase blood creatinine levels.

Instructions for use NOLIPREL

Interactions of Noliprel or Noliprel Forte

The simultaneous use of Noliprel or Noliprel Forte and lithium preparations is not recommended. Increasing lithium concentrations may result in symptoms and signs of lithium overdose (due to decreased renal excretion of lithium). If combination therapy, including ACE inhibitors and potassium-sparing diuretics, cannot be discontinued, lithium levels should be carefully monitored and the dose adjusted if necessary.

When using ACE inhibitors, the hypoglycemic effect of insulin and sulfonylurea derivatives may be enhanced. The development of hypoglycemia is extremely rare, but there is an increase in glucose tolerance and a decrease in the need for insulin.

With the simultaneous use of Noliprel or Noliprel Forte and baclofen, the hypotensive effect is enhanced (it is necessary to monitor blood pressure levels and adjust the dose of Noliprel or Noliprel Forte).

When used simultaneously with NSAIDs in case of dehydration, acute renal failure may develop (due to decreased glomerular filtration). In such cases, before starting treatment, the body should be sufficiently hydrated and the functional activity of the kidneys should be assessed. It should also be taken into account that NSAIDs weaken the hypotensive effect of ACE inhibitors. NSAIDs and ACE inhibitors have been found to have an additive effect on hyperkalemia, and a decrease in renal function is also possible.

With the simultaneous use of Noliprel or Noliprel Forte and tricyclic antidepressants, antipsychotics, the hypotensive effect may be enhanced and the risk of developing orthostatic hypotension may increase (additive effect).

GCS, tetracosactide reduce the hypotensive effect of Noliprel or Noliprel Forte (retention of water and electrolytes as a result of the action of glucocorticoids).

Interactions associated with perindopril

The combination of perindopril with potassium-sparing diuretics and potassium supplements can lead to a significant increase in the concentration of potassium in the blood serum (especially against the background of renal failure) and even death. ACE inhibitors should not be prescribed in combination with potassium-sparing diuretics and potassium supplements, except for patients with hypokalemia (with constant monitoring of the concentration of potassium in the blood plasma and ECG parameters).

ACE inhibitors may enhance the hypotensive effect of some anesthetics.

While taking ACE inhibitors, allopurinol, cytotoxic or immunosuppressive drugs, systemic corticosteroids or procainamide may lead to an increased risk of leukopenia.

Interactions associated with indapamide

With the simultaneous use of astemizole, erythromycin (for intravenous administration), pentamidine, sultopride, vincamine, halofantrine, bepridil, terfenadine and indapamide, the development of arrhythmias is possible (provoking factors include hypokalemia, bradycardia or a prolonged QT interval).

With the simultaneous use of indapamide and drugs that reduce potassium levels (including intravenous amphotericin B, gluco- and mineralocorticoids for systemic use, tetracosactide, stimulant laxatives), the risk of developing hypokalemia increases. Potassium concentration should be monitored and adjusted if necessary. If it is necessary to prescribe laxatives, drugs without a stimulating effect on intestinal motility should be used.

When used simultaneously with cardiac glycosides, it should be taken into account that low potassium levels may enhance the toxic effect of cardiac glycosides. Potassium levels and ECG should be monitored and therapy adjusted if necessary.

It should be taken into account that indapamide in combination with potassium-sparing diuretics or potassium supplements does not exclude the development of hypokalemia or hyperkalemia (especially in patients with diabetes mellitus and renal failure).

With simultaneous use of indapamide with antiarrhythmic drugs IA (quinidine, hydroquinidine, disopyramide) and class III (amiodarone, bretylium, sotalol), the development of arrhythmias is possible (provoking factors include hypokalemia, bradycardia or a prolonged QT interval). If arrhythmia develops, antiarrhythmic drugs should not be used (an artificial pacemaker must be used).

With significant dehydration of the body, which is caused by taking diuretic drugs, the risk of developing renal failure increases due to the use of iodine-containing contrast agents in high doses. Rehydration is necessary before using iodinated contrast agents.

When used simultaneously with calcium salts, it is possible to increase the calcium content in the blood plasma as a result of a decrease in its excretion in the urine.

When using indapamide against the background of constant use of cyclosporine, the level of creatinine in plasma increases even with a normal state of water-electrolyte balance.

special instructions

People who have been prescribed treatment with Noliprel need adequate dehydration of the body to prevent a sharp decrease in blood pressure.

People with heart failure may be treated with beta blockers at the same time.

When treated with Noliprel, a positive reaction is observed during a doping test.

In the first weeks of treatment, it is important to drive vehicles or operate precision machinery carefully when treating with Noliprel.

If during treatment there is a significant decrease in pressure, it may be necessary to administer 0.9% sodium chloride intravenously.

Treatment of patients with cerebral circulatory insufficiency or coronary heart disease should begin with small doses of Noliprel.

In people who have very high levels of uric acid in the blood, when treated with varieties of the drug Noliprel, the risk of developing gout .

Instructions for use NOLIPREL® A (NOLIPREL A)

Perindopril

Neutropenia, agranulocytosis

Neutropenia/agranulocytosis, thrombocytopenia and anemia were observed while taking ACE inhibitors. In patients with normal liver function and in the absence of other complicating factors, neutropenia rarely develops. Perindopril should be used with extreme caution in patients with diffuse connective tissue diseases, while taking immunosuppressants, allopurinol or procainamide, especially in patients with pre-existing liver dysfunction. Some of these patients developed severe infections, in some cases resistant to intensive antibiotic therapy. When prescribing perindopril to such patients, it is recommended to periodically monitor the number of leukocytes in the blood. Patients should report any signs of infectious diseases (eg, sore throat, fever) to their doctor.

Hypersensitivity/angioedema

When taking ACE inhibitors, incl. and perindopril, in rare cases, the development of angioedema of the face, extremities, lips, mucous membranes, tongue, vocal cords and/or larynx may occur. These reactions may occur at any time during therapy. In such cases, the drug should be stopped immediately and the necessary monitoring should be carried out until the symptoms disappear completely. If the swelling affects only the face and lips, it usually goes away on its own, although antihistamines can be used to treat symptoms.

Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, vocal cords, or larynx can lead to airway obstruction. If these symptoms appear, you should immediately administer epinephrine solution 1:

• 1000 (0.3-0.5 ml) subcutaneously and/or ensure airway patency.

There are reports that black patients are more likely to experience angioedema when treated with ACE inhibitors than patients of other races.

Patients who have had angioedema not associated with taking ACE inhibitors may have an increased risk of developing it when taking drugs of this group.

In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. In this case, patients experience abdominal pain (with or without nausea and vomiting), in some cases, without previous angioedema of the face and with normal C1-esterase levels. The diagnosis is made using computed tomography of the abdominal region, ultrasound, or at the time of surgery. Symptoms disappear after stopping ACE inhibitors. Therefore, in patients with abdominal pain receiving ACE inhibitors, when carrying out differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine.

Anaphylactoid reactions during desensitization

There are isolated reports of the development of persistent, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with hymenopteric venom (including bee and aspen). ACE inhibitors should be prescribed with extreme caution to patients prone to allergic reactions and undergoing desensitization; their use should be avoided in patients undergoing immunotherapy with insect venom allergens. However, if the patient requires both treatment with ACE inhibitors and desensitization, then the onset of such reactions can be prevented by temporarily stopping the use of ACE inhibitors at least 24 hours before starting the course of desensitization therapy.

Anaphylactoid reactions during LDL apheresis

In rare cases, life-threatening anaphylactoid reactions may occur in patients receiving ACE inhibitors during LDL apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be temporarily discontinued before each apheresis procedure.

Patients on hemodialysis

Anaphylactoid reactions have been reported in some patients undergoing hemodialysis using high-flux membranes (eg, AN69®) and concomitantly receiving one of the ACE inhibitors. For such patients, the use of a different type of membrane or a different class of antihypertensive drug should be considered.

Cough

Taking an ACE inhibitor may cause a dry cough. The cough persists for a long time while taking the drug, but disappears when the drug is discontinued. This symptom may have an iatrogenic etiology. If the need to take an ACE inhibitor remains, then continued treatment should be considered.

Risk of arterial hypotension and/or renal failure (in case of heart failure, water and electrolyte deficiency)

With significant loss of water and electrolytes (strict salt-free diet or long-term treatment with diuretics), especially in patients with initially low blood pressure, with renal artery stenosis, congestive heart failure or cirrhosis of the liver, accompanied by edema and ascites, pronounced stimulation of the RAAS occurs. Therefore, inhibition of RAAS activity when taking an ACE inhibitor may lead to a sudden decrease in blood pressure and/or an increase in serum creatinine, indicating functional renal failure. This is most likely when you first take the drug and during the first 2 weeks of treatment. In some, albeit very rare cases, such a disorder develops acutely, and the onset of the process is difficult to predict. In such cases, treatment should be resumed with a lower dose, gradually increasing it.

Elderly patients

Before starting treatment, kidney function and potassium levels should be monitored. To avoid sudden arterial hypotension, the initial dose of the drug is adjusted depending on the degree of decrease in blood pressure, especially in the case of dehydration and loss of electrolytes.

Patients with established atherosclerosis

The risk of arterial hypotension exists in all patients, but the drug should be used with extreme caution in patients with coronary artery disease or cerebrovascular insufficiency. In such cases, treatment should be started with a low dose.

Renovascular hypertension

Renovascular hypertension is treated by revascularization. However, the use of ACE inhibitors may be beneficial in patients with renovascular hypertension awaiting surgery or when surgery is not available.

In patients with an established diagnosis of renal artery stenosis or if it is suspected, treatment with Noliprel® A should begin in the hospital with a small dose under monitoring of renal function and potassium levels, because Some patients developed renal failure, which was reversible when treatment was discontinued.

Other risk groups

In patients with severe acute heart failure (grade IV) and in patients with insulin-dependent diabetes mellitus (a tendency to spontaneously increase potassium levels), treatment with Noliprel® A should be started with low doses and carried out under constant medical supervision.

Patients with arterial hypertension and coronary insufficiency should not stop taking beta-blockers:

• An ACE inhibitor should be used in addition to a beta blocker.

Diabetes

In diabetic patients already taking oral hypoglycemic agents or insulin, glycemic levels should be carefully monitored, especially during the first month of taking an ACE inhibitor.

Ethnic differences

Perindopril, like other ACE inhibitors, may have a less pronounced hypotensive effect in patients of black race compared to representatives of other races. Perhaps this difference is due to the fact that arterial hypertension in patients of the Negroid race very often occurs against the background of low renin activity.

Surgery/anesthesia

ACE inhibitors can cause a drop in blood pressure during anesthesia, especially if the anesthetic used has a hypotensive effect. Therefore, long-acting ACE inhibitors such as perindopril should, if possible, be discontinued 24 hours before surgery.

Aortic or mitral valve stenosis/hypertrophic cardiomyopathy

Use ACE inhibitors with caution in patients with left ventricular outflow tract obstruction.

Liver dysfunction

In rare cases, ACE inhibitors have been associated with a syndrome that begins with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not yet clear. In patients receiving ACE inhibitors, if jaundice or a marked increase in liver enzyme activity develops, the ACE inhibitor should be discontinued and a thorough medical examination should be performed.

Hyperkalemia

Elevated serum potassium levels have been reported in some patients treated with ACE inhibitors, including perindopril. Risk factors for the development of hyperkalemia include renal failure, deterioration of renal function, age (> 70 years), diabetes mellitus, intercurrent events such as dehydration, acute heart failure, metabolic acidosis, concomitant use of potassium-sparing diuretics (eg, spironolactone, eplerenone, triamterene or amiloride), potassium supplements or potassium-containing salt substitutes, or taking other drugs that cause increases in serum potassium (eg, heparin). Taking potassium supplements, potassium-sparing diuretics, or potassium-containing salt substitutes, especially in patients with impaired renal function, may result in significant increases in serum potassium levels. Hyperkalemia can cause serious arrhythmias, sometimes fatal. If concomitant administration of perindopril or the above drugs is considered necessary, they should be taken with caution and with regular monitoring of serum potassium levels.

Indapamide

In patients with impaired liver function, taking thiazide and thiazide-like diuretics can cause hepatic encephalopathy. In this case, the diuretic should be stopped immediately.

Photosensitivity

Cases of photosensitivity have been reported with the use of thiazide and thiazide-like diuretics. If photosensitivity is noted during treatment, it is recommended to stop taking the drug. If re-administration of a diuretic is considered necessary, it is recommended to protect the skin from the sun and artificial UV radiation.

Water and electrolyte balance

Sodium level.

Before starting treatment, it is necessary to evaluate the sodium content, and further such studies should be carried out regularly. Taking any diuretic medication can cause a decrease in sodium levels, which sometimes leads to a number of serious complications. Initially, a decrease in sodium levels may be asymptomatic, which is why it is necessary to regularly monitor its content. In elderly patients and patients with liver cirrhosis, monitoring should be carried out even more often.

Potassium level.

The main danger when taking thiazide and thiazide-like diuretics is potassium deficiency and, accordingly, hypokalemia. Consideration of the risk of potassium levels falling below acceptable levels (< 3.4 mmol/L) is necessary in persons at increased risk, such as elderly patients and/or patients with impaired or malnutrition, regardless of whether they are taking one or more medications drugs, in patients with liver cirrhosis, which is accompanied by edema and ascites, in patients with coronary artery disease and in patients with heart failure. In such cases, hypokalemia increases the toxicity of cardiac glycosides and increases the risk of developing arrhythmias. Patients with congenital or iatrogenic prolongation of the QT interval are also at risk. Hypokalemia, like bradycardia, is a risk factor for the development of serious cardiac arrhythmias, especially torsade de pointes (TdP), which can be fatal. In any case, potassium levels should be monitored as often as possible. The first determination of plasma potassium should be carried out within the first week after the start of treatment. If potassium levels decrease, dose adjustment is necessary.

Calcium level.

Thiazide and thiazide-like diuretics can reduce the excretion of calcium in the urine, which leads to a temporary and slight increase in the concentration of calcium in the blood. A marked increase in calcium levels may be associated with undiagnosed hyperparathyroidism. In this case, treatment should be stopped until the function of the parathyroid gland is examined.

Blood glucose level

In patients with diabetes mellitus, it is necessary to constantly monitor blood glucose levels, especially if potassium levels are simultaneously low.

Uric acid

Patients with high levels of uric acid in the blood may be predisposed to developing gout.

Effect on kidney function

Thiazide and thiazide-like diuretics are most effective when renal function is normal or only slightly impaired (serum creatinine is below approximately 2.5 mg/dL, i.e. 220 µmol/L for an adult patient). In elderly patients, plasma creatinine levels should be adjusted for age, weight and gender using the Cockcroft formula:

For men: CC (ml/min) = (140 – age) x body weight (kg)/0.814 x serum creatinine (µmol/l)

For women:

• the calculation result should be multiplied by 0.85.

At the beginning of treatment, taking diuretics can lead to loss of water and sodium, which in turn leads to hypovolemia. Hypovolemia causes a decrease in glomerular filtration rate. It may be accompanied by an increase in creatinine and urea in the blood. This renal failure is temporary and does not cause undesirable consequences in patients with normal renal function, but in cases of existing impairment, renal failure may worsen.

Athletes

Please note that indapamide may cause a positive reaction during doping control.

Noliprel® A

When taking the combined drug Noliprel® A in low doses, there was no significant reduction in adverse reactions to the drug, except for hypokalemia, compared to the use of the drug components separately. If a patient simultaneously starts taking two new antihypertensive drugs, then an increase in the development of manifestations of idiosyncrasy cannot be ruled out. To minimize this risk, careful monitoring of the patient's condition should be carried out.

The combination of lithium and the combination of perindopril with indapamide is generally not recommended.

Kidney failure.

In patients with severe renal failure (creatinine clearance <30 ml/min), this combination is contraindicated. Treatment should be stopped if a patient suffering from arterial hypertension without visible kidney damage is found to have renal failure during a blood test (renal complex). Treatment can be resumed either with this combination at lower doses or with only one component. Such patients should usually undergo frequent monitoring of serum creatinine and potassium levels for the first time - after 2 weeks of treatment, then once every 2 months during the period of therapeutic stability.

Renal failure was mainly observed in patients with acute heart failure and was also observed in renal artery stenosis. This drug is generally not recommended for patients with bilateral renal artery stenosis or for patients with only one kidney.

Arterial hypotension, deficiency of water and electrolytes.

The risk of a sudden drop in blood pressure increases with low sodium levels (especially in patients with renal artery stenosis). Therefore, during treatment, the state of water and electrolyte balance should be periodically monitored, which may be disturbed due to diarrhea or vomiting. In case of severe arterial hypotension, intravenous infusion of an isotonic solution may be necessary.

Transient arterial hypotension is not a contraindication for continued treatment. After restoration of adequate blood volume and blood pressure, treatment can be resumed either with this combination at lower doses, or with only one component.

Potassium content.

The combination of perindopril and indapamide does not prevent the onset of hypokalemia, especially in patients with diabetes mellitus and in patients with renal failure. As with any antihypertensive drug taken in combination with a diuretic, plasma potassium levels should be regularly monitored during treatment with this combination.

Excipients.

Noliprel® A should not be prescribed to patients with lactose intolerance, lapp lactase deficiency (lactase deficiency of some peoples of the North) or impaired absorption of glucose-galactose.

Use in pediatrics

The effectiveness and tolerability of perindopril in children and adolescents as mono- or as part of combination therapy has not been sufficiently studied.

Impact on the ability to drive vehicles and operate machinery

Perindopril and indapamide in the form of monotherapy or in combination as part of the drug Noliprel® A do not affect the ability to concentrate and the speed of psychomotor reactions. However, in some patients, especially at the beginning of treatment or when combined with another antihypertensive drug, individual reactions may develop with a decrease in blood pressure. This leads to impaired ability to drive vehicles or other mechanisms.

Results of preclinical safety studies

The toxicity of the perindopril/indapamide combination is slightly higher than the toxicity of each component. No renal toxicity was detected in rats. However, this combination causes gastrointestinal toxicity in dogs; in rats, the toxic effect on the maternal body increases (compared to perindopril). These undesirable effects occurred at doses with a very high safety margin compared to the therapeutic doses used.

Preclinical studies conducted separately with perindopril and indapamide revealed neither genotoxic nor teratogenic potential.

Noliprel's analogs

Level 4 ATX code matches:
Akkuzid

Enap-N

Iruzid

Co-Diroton

Enalozide

Enap NL

Enapril-N

Capozide

Tritace Plus

Enzix

Liprazid

Co-Renitec

Hartil N

Hartil D

Ko-Perineva

Kaptopres

Analogs of Noliprel, as well as the drugs Noliprel A Bi Forte, Noliprel A Forte, are other drugs that are used to lower blood pressure and contain similar active ingredients, that is, perindopril and indapamide. Such drugs are Co-prenesa , Prestarium , etc. The price of analogues may be lower than the cost of Noliprel and its varieties.

During pregnancy and lactation

For pregnant women and mothers while breastfeeding , the use of Noliprel is contraindicated. Systematic treatment with these drugs can lead to the development of abnormalities and diseases in the fetus, as well as lead to fetal death. If a woman finds out she is pregnant during treatment, there is no need to terminate the pregnancy, but the patient should be aware of the possible consequences. If blood pressure increases, other antihypertensive therapy is prescribed. If a woman took this drug in the second and third trimesters, an ultrasound of the fetus should be performed to evaluate the condition of its skull and kidney function.

Newborns whose mothers took the drug may suffer from manifestations of arterial hypotension, so they need to be constantly monitored by specialists.

When feeding with breast milk, the drug is contraindicated, so lactation should be stopped during therapy or another drug should be selected.

Reviews of Noliprel

Reviews on forums about Noliprel, as well as about the drugs Noliprel A, Noliprel A Forte, Noliprel A Bi Forte, indicate that this drug effectively lowers blood pressure. The medicine maintains normal blood pressure, reducing the likelihood of strokes and myocardial infarction.

Reviews of Noliprel Forte also often contain information that this medicine and its other varieties allow you to get a positive result in cases where other drugs are ineffective. Sometimes patients note the development of some side effects, in particular, dry cough, headache, but they are not very intense.

Doctors also note the positive effect of the drug, but they always note that the drug must be taken strictly according to the instructions and taking into account the recommendations of a specialist. In particular, the drug should be taken regularly, and not only during periods of intense surges in blood pressure.

Noliprel price, where to buy

The price of Noliprel is on average 500 rubles per pack of 30 pcs. The price in Moscow for Noliprel A is from 500 to 550 rubles. The price for Noliprel Forte is from 550 rubles per package. Noliprel A Forte 5 mg can be purchased at a price of 650 rubles. The cost of Noliprel A Bi Forte is from 700 rubles. per pack 30 pcs.

• Online pharmacies in RussiaRussia
• Online pharmacies in UkraineUkraine
• Online pharmacies in KazakhstanKazakhstan

ZdravCity

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Pharmacy24

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PaniPharmacy

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