Noliprel Bi-Forte film-coated tablets packaging 90 pcs (3664898105468) Servier (France) - instructions, buy at a low price in Ukraine

Contraindications

Related to perindopril:

hypersensitivity to the active substance or to any other ACE inhibitor
history of angioedema (Quincke's edema) associated with previous treatment with ACE inhibitors
congenital or idiopathic angioedema
pregnancy or planning pregnancy;
simultaneous use with drugs containing aliskiren in patients with diabetes mellitus or impaired renal function (glomerular filtration rate <60 ml/min/1.73 m2);
simultaneous use with sacubitril/valsartan;
extracorporeal treatments that bring blood into contact with negatively charged surfaces;
significant bilateral renal artery stenosis or stenosis of the artery of a single kidney.

Related to indapamide:

hypersensitivity to the active substance or any other sulfonamides;
severe to moderate renal impairment (creatinine clearance <60 ml/min)
hepatic encephalopathy
severe liver dysfunction;
hypokalemia
as a general rule, this drug should not be prescribed in combination with antiarrhythmic drugs that can cause the development of paroxysmal ventricular tachycardia of the “pirouette” type;
breastfeeding period.

Related to the drug Noliprel® Bi-forte:

hypersensitivity to any excipient.

Due to the lack of sufficient clinical experience, Noliprel® Bi-forte should not be used:

patients on hemodialysis;
patients with untreated decompensated heart failure.

Instructions for use NOLIPREL® BI-FORTE (NOLIPREL BI-FORTE)

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

Perindopril

Neutropenia, agranulocytosis, thrombocytopenia, anemia

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 taking ACE inhibitors than non-black patients.

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, abdominal pain is noted (with or without nausea and vomiting), in some cases, without previous angioedema of the face and with a normal level of C1-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. 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.

Potassium-sparing diuretics, potassium salts

Usually, the combined use of perindopril with potassium-sparing diuretics or potassium salts is not recommended.

Double blockade of the RAAS

There is evidence that the combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of hypotension, hyperkalemia and renal dysfunction (including acute renal failure). In this regard, double blockade of the RAAS by combined use of an ACE inhibitor and an angiotensin II receptor antagonist or aliskiren is not recommended.

If dual blockade of the RAAS is considered absolutely necessary, it should be carried out under specialist supervision and with careful frequent monitoring of renal function, blood pressure and electrolytes.

Patients with diabetic nephropathy should not take ACE inhibitors and angiotensin II receptor antagonists concomitantly.

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.

Patients with an established diagnosis of renal artery stenosis or if it is suspected are not recommended to prescribe Noliprel® Bi-Forte, because in such cases, treatment with the perindopril/indapamide combination should be started in a hospital and lower doses should be used than a single dose of Noliprel® Bi-Forte.

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 the Negroid 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

ACE inhibitors should be used 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

In some patients treated with ACE inhibitors, including perindopril, cases of increased serum potassium levels were observed. 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) × body weight (kg)/0.814 × 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® Bi-forte

Kidney failure

For patients with moderate to severe renal failure (creatinine clearance <60 ml/min), Noliprel® Bi-forte is contraindicated.

Treatment should be discontinued if a blood test reveals renal failure in a patient suffering from arterial hypertension and without clinical symptoms of kidney damage. Treatment can be resumed with the drug at a lower dose, or with only one of the components.

Routine medical monitoring of these patients should include frequent monitoring of serum potassium and creatinine levels, initially 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 or underlying renal impairment, including renal artery stenosis.

It is not recommended to use Noliprel® Bi-forte in patients with bilateral renal artery stenosis or in patients with a solitary kidney.

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® Bi-forte 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 is taken in addition to a beta blocker.

Arterial hypotension, deficiency of water and electrolytes in the body

With low sodium levels, especially in patients with renal artery stenosis, there is a risk of a sudden drop in blood pressure. Therefore, tests should be systematically carried out to identify clinical signs of deficiency in the body of water and electrolytes, which may occur against the background of attacks of diarrhea or vomiting. Plasma electrolyte levels should be regularly monitored.

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 satisfactory blood volume and blood pressure, treatment can be resumed either with the drug at a lower dose, or with only one of its components.

Potassium level

The combination of perindopril and indapamide does not prevent the onset of hypokalemia, especially in patients with diabetes mellitus or in patients with renal failure. As with any antihypertensive drug containing a diuretic, regular monitoring of plasma potassium levels should be carried out.

Excipients

Noliprel® Bi-forte should not be prescribed to patients with hereditary lactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption syndrome.

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® Bi-forte do not affect the ability to concentrate. 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.

Preclinical safety data

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.

Perindopril

In chronic oral toxicity studies (in rats and monkeys), the receptor organ is the kidney, and the damage is reversible.

No mutagenicity was observed in in vitro or in vivo studies.

Reproductive toxicity studies (in rats, mice, rabbits and monkeys) showed no evidence of embryotoxicity or teratogenicity. However, ACE inhibitors as a class have been shown to have adverse effects on late fetal development, leading to fetal death and congenital defects in rodents and rabbits:

kidney damage and an increase in perinatal and postnatal mortality were observed.

No carcinogenicity was observed in studies with long-term administration in rats and mice.

Indapamide

When indapamide was administered orally in the highest doses to different types of animals (doses 40-8000 times higher than the therapeutic dose), an increase in the diuretic effect was observed. In acute toxicity studies of indapamide administered intravenously or intraperitoneally, the main symptoms of poisoning were related to the pharmacological effects of indapamide, such as bradypnea and peripheral vasodilation.

When indapamide was tested for mutagenicity and carcinogenicity, negative results were obtained.

Features of application

Pregnancy

The drug is contraindicated for use by pregnant women or women planning pregnancy.

Children

Noliprel® Bi-forte should not be used to treat children and adolescents. The safety and effectiveness of perindopril arginine/indapamide in pediatric patients has not been established. No data available.

Drivers

The two active ingredients, when used separately or in combination as Noliprel® Bi-forte, do not affect the ability to drive vehicles or use other mechanisms, but some patients may experience individual reactions associated with a decrease in blood pressure, especially at the beginning of treatment or when used simultaneously with other antihypertensive drugs. As a result, the ability to drive vehicles or operate other machinery may deteriorate.

Overdose

In case of overdose, a common adverse reaction is arterial hypotension, which can sometimes be accompanied by nausea, vomiting, convulsions, dizziness, drowsiness, confusion, oliguria, which can progress to anuria (due to hypovolemia), as well as circulatory shock. Disturbances in water and electrolyte balance (decreased levels of potassium and sodium in the blood plasma), renal failure, hyperventilation, tachycardia, rapid heartbeat (palpitation), bradycardia, anxiety, cough may occur.

Side effects

The use of perindopril inhibits the renin-angiotensin-aldosterone system and helps reduce the loss of potassium in the blood plasma caused by indapamide. Hypokalemia (potassium level <3.4 mmol/l) occurs in 6% of patients treated with Noliprel® Bi-forte. The most frequently reported adverse reactions were: when using perindopril - dizziness, headache, paresthesia, dysgeusia, visual disturbances, vertigo, tinnitus, hypotension, cough, shortness of breath, abdominal pain, constipation, dyspepsia, diarrhea, nausea , vomiting, itching, rash, muscle cramps and asthenia when using indapamide - hypersensitivity reactions, mainly dermatological, in patients prone to developing allergic and asthmatic reactions, and maculopapular rashes.

Description of the drug INDAPRIL

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. When resuming combination therapy, the components should be used in low doses or only one of them should be used. Such patients require regular monitoring of potassium levels and creatinine concentrations 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.

In the case of initial hyponatremia, there is a risk of sudden development of arterial hypotension, especially in patients with renal artery stenosis. Therefore, during dynamic monitoring of patients, attention should be paid to possible symptoms of dehydration and decreased electrolyte levels in the blood plasma, for example, after diarrhea or vomiting. Such patients require regular monitoring of blood plasma electrolyte 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 with the combination of any antihypertensive drug and a diuretic, regular monitoring of plasma potassium levels is necessary.

The simultaneous administration of perindopril and potassium-sparing diuretics, as well as potassium supplements, potassium-containing table salt substitutes and food additives is not recommended.

In patients with normal renal function and without concomitant risk factors, neutropenia rarely occurs. Perindopril should be used with extreme caution against the background of systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), as well as while taking immunosuppressants, allopurinol or procainamide, or a combination of these factors, especially in patients with initially impaired renal function . 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.

When taking ACE inhibitors, including perindopril, in rare cases, the development of angioedema of the face, extremities, lips, tongue, vocal folds and/or larynx may occur. This can happen at any time during treatment. If symptoms appear, the drug should be stopped immediately and the patient should be observed until signs of edema completely disappear. If the swelling affects only the face and lips, it usually goes away on its own, although antihistamines can be used as symptomatic therapy. Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, vocal folds, or larynx can lead to airway obstruction. If such symptoms appear, you should immediately begin appropriate therapy, for example, administer subcutaneous epinephrine (adrenaline) in dilution 1:

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

A higher risk of developing angioedema has been reported in black patients.

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.

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.

There are isolated reports of the development of prolonged, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with hymenoptera venom (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, anaphylactoid reaction can be avoided by temporary withdrawal.

In rare cases, life-threatening anaphylactoid reactions have developed 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.

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.

In some pathological conditions, significant activation of the RAAS may be observed, especially with severe hypovolemia and a decrease in plasma electrolytes (due to a salt-free diet or long-term use of diuretics), in patients with initially low blood pressure, renal artery stenosis, 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 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 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 it.

Before starting to take the drug, it is necessary to assess the functional activity of the kidneys and the potassium content 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.

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.

Treatment with the combination of perindopril/indapamide 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 levels in the blood plasma. Some patients may develop functional renal failure, which disappears when this combination is discontinued.

In persons with severe heart failure (NYHA functional class IV) and patients with type 1 diabetes mellitus (risk of spontaneous increase in potassium levels), treatment should begin with a low dose of the drug and under close medical supervision.

During the first month of therapy with ACE inhibitors, plasma glucose concentrations should be carefully monitored in patients with diabetes mellitus and treated with oral hypoglycemic agents or insulin.

Perindopril, like other ACE inhibitors, apparently has a less pronounced antihypertensive effect in patients of the Black race compared to representatives of other races. This difference may be due to the fact that black patients with arterial hypertension are more likely to have low renin activity.

Carrying out general anesthesia while using ACE inhibitors can lead to a significant decrease in blood pressure, especially when using general anesthesia agents that have a hypotensive effect. It is recommended, if possible, 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.

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.

Hyperkalemia may develop during treatment with ACE inhibitors, incl. and perindopril. Hyperkalemia can cause serious, sometimes fatal, abnormal heart rhythms. Risk factors for hyperkalemia are renal failure, deterioration of renal function, age over 70 years, diabetes mellitus, certain concomitant conditions (dehydration, acute decompensation of heart failure, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone and its derivative eplerenone, triamterene, amiloride ), as well as a number of medicines. In such cases, treatment should be carried out with caution and regular monitoring of serum potassium levels.

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 elderly patients.

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, malnourished patients (both those receiving and not receiving concomitant drug therapy), patients with liver cirrhosis (with edema and ascites), coronary artery disease, heart failure. Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of developing arrhythmias.

Patients with a prolonged QT interval, either congenital or drug-induced, are also at increased risk.

Hypokalemia, like bradycardia, contributes to the development of severe heart rhythm disturbances, especially polymorphic ventricular tachycardia of the “pirouette” type, 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 content 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 may reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in plasma calcium concentrations. Severe hypercalcemia may be a consequence of previously undiagnosed hyperparathyroidism. Before studying the function of the parathyroid glands, you should stop taking diuretics.

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

When the concentration of uric acid in the blood plasma increases during therapy, the frequency of gout attacks may increase.

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

At the beginning of diuretic treatment, patients may experience a temporary decrease in GFR and an increase in plasma urea and creatinine concentrations due to hypovolemia and hyponatremia. This transient functional renal failure is not dangerous for patients with initially normal renal function, but its severity may increase in patients with renal failure.

Indapamide may give a positive reaction during doping control.

Impact on the ability to drive vehicles and machinery

The action of indapamide and perindopril, either individually or in combination, does not lead to impaired psychomotor reactions. However, some people may develop different individual reactions in response to lowering blood pressure, especially at the beginning of treatment or when other antihypertensive drugs are added to the therapy. In this case, the ability to drive a car or operate other machinery may be reduced.

Interaction

Potassium-sparing diuretics (amiloride, spironolactone, triamterene). Despite the rationality of prescribing this combination to some patients, hypokalemia or hyperkalemia may occur (especially in patients with renal failure or diabetes mellitus). Plasma potassium levels should be monitored, ECG monitoring should be performed, and therapy should be reviewed if necessary.

Metformin. May lead to lactic acidosis due to the development of functional renal failure associated with taking diuretics, especially loop diuretics. Metformin should not be used if plasma creatinine levels exceed 15 mg/L (135 µmol/L) in men and 12 mg/L (110 µmol/L) in women.

Iodine contrast agents. In case of dehydration caused by the use of diuretics, there is a risk of developing acute renal failure, especially when using large doses of iodine contrast agents. Before using iodine contrast agents, it is necessary to restore the water balance.

Calcium (salts). There is a risk of increased calcium levels in the blood due to decreased excretion in urine.

Cyclosporine, tacrolimus. There is a risk of an increase in blood creatinine without changing the concentration of circulating cyclosporine, even in the absence of water and sodium deficiency.

Corticosteroids, tetracosactide (systemic action). Reduce the antihypertensive effect (retention of water and sodium ions under the influence of corticosteroids).

Noliprel A Bi forte, tablets coated. captivity. about. 10+2.5 mg, 30 pcs.

General instructions for perindopril and indapamide

Lithium preparations

The combined use of a combination of perindopril and indapamide with lithium preparations is usually not recommended (see section “Drug Interactions”).

Renal dysfunction

Therapy with the drug Noliprel® A Bi-forte is contraindicated in patients with moderate and severe renal impairment (creatinine clearance less than 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 only one of the drugs.

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 subsequently every 2 months during the period when the dose is selected. Renal failure occurs more often in patients with severe chronic heart failure or underlying renal failure, incl. with renal artery stenosis.

The drug Noliprel® A Bi-forte is not recommended for use in cases of bilateral renal artery stenosis or in the case of a single functioning kidney.

Arterial hypotension and water-electrolyte imbalance

In the case of initial hyponatremia, there is a risk of sudden development of arterial hypotension, especially in patients with renal artery stenosis. Therefore, systematic assessment of symptoms of dehydration and decreased plasma electrolyte levels, such as after diarrhea or vomiting, is necessary. Such patients require regular monitoring of blood plasma electrolyte levels.

In case of severe arterial hypotension, intravenous administration of an isotonic saline solution may be required.

Transient arterial hypotension is not a contraindication for continued therapy. After restoration of blood volume and blood pressure, you can resume therapy, or use only one of the components of the drug.

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 any antihypertensive drug in combination with a diuretic, regular monitoring of the concentration of potassium ions in the blood plasma is necessary.

Excipients

The drug Noliprel® A Bi-forte is contraindicated in patients with hereditary galactose intolerance, complete lactase deficiency and glucose-galactose malabsorption.

Sodium content

Noliprel® A Bi-forte contains less than 1 mmol sodium (23 mg) per tablet, i.e. Contains virtually no sodium.

Childhood

The drug Noliprel® A Bi-forte is contraindicated in 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 and indapamide, both separately and together in patients of this age group.

Indapamide

Hepatic encephalopathy

In the presence of liver dysfunction, taking thiazide and thiazide-like diuretics can lead to the development of hepatic encephalopathy. In such a situation, you should immediately stop taking the diuretic.

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 ultraviolet rays.

Water and electrolyte balance

Concentration of sodium ions in blood plasma. The concentration of sodium ions in the blood plasma must be determined before starting treatment, and then regularly monitored while taking the drug. A decrease in the concentration of sodium ions 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 elderly patients (see sections “Side effects” and “Overdose”). Treatment with any diuretics can cause hyponatremia, sometimes with very serious consequences. Hyponatremia accompanied by hypovolemia can lead to dehydration and orthostatic hypotension. A concomitant decrease in the content of chlorine ions can lead to the development of secondary compensatory metabolic alkalosis: the frequency of its occurrence and severity are insignificant.

Concentration of potassium ions in blood plasma. Potassium depletion with hypokalemia is the main risk associated with therapy with thiazide and thiazide-like diuretics. It is necessary to prevent the risk of a decrease in the concentration of potassium ions (less than 3.4 mmol/l) in the following categories of high-risk patients: elderly and/or malnourished patients, both receiving and not receiving concomitant drug therapy, patients with cirrhosis of the liver, with edema or ascites, ischemic heart disease, heart failure. Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of arrhythmia.

Patients with a prolonged QT interval, either congenital or drug-induced, are also at increased risk.

Hypokalemia, as well as bradycardia, contributes to the development of severe cardiac arrhythmias, especially polymorphic ventricular tachycardia of the “pirouette” type, which can be fatal. In all the cases described above, more frequent 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 correction should be made.

Concentration of calcium ions in blood plasma. Thiazide and thiazide-like diuretics can reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in the concentration 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

Patients with elevated plasma uric acid concentrations tend to have an increased incidence of gout attacks.

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 2.5 mg/l or 220 µmol/l).

In elderly patients, plasma creatinine levels should be assessed taking into account age, weight and sex, according to the Cockroft formula:

For older men:

where: age in years, weight in kg, plasma creatinine concentration in µmol/l.

For older women:

the result obtained should be multiplied by a factor of 0.85.

At the beginning of diuretic treatment in patients, due to hypovolemia (due to the excretion of water and sodium ions), a temporary decrease in GFR and an increase in the concentration of urea and creatinine in the blood plasma may be observed. This transient functional renal failure does not have adverse consequences for patients with normal renal function, but may aggravate pre-existing renal impairment before treatment.

Athletes

Athletes should pay attention to the fact that the drug contains an active substance that can give a positive result during a doping test.

Acute myopia and secondary angle-closure glaucoma

Sulfonamides and their derivatives can cause the development of idiosyncratic reactions leading to temporary (transient) myopia and acute angle-closure glaucoma. Without proper treatment, acute angle-closure glaucoma can lead to vision loss. First of all, you need to stop taking the drug as soon as possible. If intraocular pressure continues to be high, immediate medical or surgical treatment may be required. Risk factors that can lead to the development of acute angle-closure glaucoma include an allergy to sulfonamide or penicillin.

Perindopril

Double blockade of the RAAS

There is evidence of an increased risk of arterial hypotension, hyperkalemia and decreased renal function (including acute renal failure) when ACE inhibitors are used together with ARB II or aliskiren. Therefore, double blockade of the RAAS by combining an ACE inhibitor with ARA II or aliskiren is not recommended (see sections “Drug interactions” and “Pharmacological action”, subsection “Pharmacodynamics”). If a double blockade is absolutely necessary, then the drugs should be used under the strict supervision of a specialist with regular monitoring of renal function, plasma electrolytes and blood pressure. The use of ACE inhibitors in combination with ARB II is contraindicated in patients with diabetic nephropathy and is not recommended in other patients (see section "Contraindications").

Potassium-sparing diuretics, potassium supplements, potassium-containing table salt substitutes and food supplements

The simultaneous administration of perindopril and potassium-sparing diuretics, as well as potassium preparations, potassium-containing table salt substitutes and food additives is not recommended (see section “Drug Interactions”).

Neutropenia/agranulocytosis/thrombocytopenia/anemia

There are reports of the development of neutropenia/agranulocytosis, thrombocytopenia and anemia while taking ACE inhibitors. In patients with normal renal function and without concomitant risk factors, neutropenia rarely occurs. Perindopril should be used with extreme caution against the background of systemic connective tissue diseases, as well as while taking immunosuppressants, allopurinol or procainamide, or a combination of these factors, especially in patients with initially impaired renal function.

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 report any signs of infectious diseases (eg, sore throat, fever) to the doctor (see sections "Side effects" and "Drug interactions").

Anemia may develop in patients after kidney transplantation or in patients undergoing 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.

A slight decrease in hemoglobin 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 carried out regularly.

Renovascular hypertension

In patients with bilateral renal artery stenosis or arterial stenosis of a single functioning kidney, the risk of developing arterial hypotension and renal failure increases while using an ACE inhibitor (see section “Contraindications”). Taking diuretics may be an additional risk factor (see section "Contraindications"). Deterioration of renal function can be observed with even a slight change in serum creatinine concentration, even in patients with unilateral renal artery stenosis.

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

Treatment with the drug Noliprel® A Bi-forte is not indicated in patients with diagnosed or suspected renal artery stenosis, because Therapy should be started in a hospital setting with lower doses of the combination of perindopril and indapamide.

Hypersensitivity/angioedema

When taking ACE inhibitors, incl. and perindopril, in rare cases, the development of angioedema of the face, extremities, lips, tongue, vocal folds and/or larynx may occur. This can happen at any time during therapy. If symptoms occur, perindopril should be discontinued immediately and the patient should be observed until signs of edema have completely resolved. If the swelling affects only the face and lips, it usually goes away on its own, although antihistamines can be used as symptomatic therapy.

Angioedema, which is accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, vocal folds, or larynx can lead to airway obstruction. If such symptoms appear, you should immediately begin appropriate therapy, for example, administer epinephrine (adrenaline) subcutaneously at a dilution of 1:1000 (0.3 to 0.5 ml) or ensure airway patency.

A higher risk of developing angioedema has been reported in black patients.

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 C1-esterase. The diagnosis is made using abdominal CT, ultrasound, or at the time of surgery. Symptoms disappear after stopping ACE inhibitors. 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.

Combined use with combination drugs containing valsartan + sacubitril

The combined use of perindopril with combination drugs containing valsartan + sacubitril is contraindicated, because increased risk of developing angioedema (see section “Contraindications”). The use of a combination drug containing valsartan + sacubitril is possible no earlier than 36 hours after the last dose of perindopril. The use of perindopril is possible no earlier than 36 hours after stopping the combination drug containing valsartan + sacubitril (see sections “Contraindications” and “Drug interactions”). When ACE inhibitors are used concomitantly with other neprilysin inhibitors (for example, racecadotril), the risk of developing angioedema may be increased. In patients receiving perindopril therapy, a careful risk/benefit assessment should be performed before initiating treatment with neprilysin inhibitors (eg, racecadotril).

mTOR (mammalian target of rapamycin) inhibitors (eg, sirolimus, everolimus, temsirolimus)

In patients concomitantly receiving therapy with mTOR inhibitors (for example, sirolimus, everolimus, temsirolimus), the risk of developing angioedema (including swelling of the airways or tongue, with or without impairment of respiratory function) is increased (see section "Drug Interactions" ).

Anaphylactoid 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 bees, wasps). ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. The use of an ACE inhibitor should be avoided in patients receiving immunotherapy with hymenoptera venom. However, in patients who require both the use of an ACE inhibitor and a desensitization procedure, 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

Patients on hemodialysis

Primary hyperaldosteronism

Patients with primary hyperaldosteronism are usually not susceptible to antihypertensive drugs that act by inhibiting the RAAS. Therefore, the use of the drug in such patients is not recommended.

Cough

During therapy with an ACE inhibitor, a dry persistent cough may occur, which disappears after discontinuation of the drug. 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, it is possible to continue taking the drug.

Children

The effectiveness and tolerability of perindopril in children and adolescents as monotherapy or in combination with other drugs has not been established.

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 (due to a salt-free diet or long-term use of diuretics), in patients with initially low blood pressure, with renal artery stenosis, congestive heart failure or cirrhosis of the liver 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 2 weeks of therapy. In rare cases, these conditions develop acutely and during other periods of therapy. In such cases, it is recommended to restart therapy at a lower dose and then gradually increase the dose.

Elderly patients

Before starting to take perindopril, it is necessary to assess the functional activity of the kidneys and the concentration 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, but the drug should be used with extreme caution in patients with coronary artery disease and cerebrovascular insufficiency. In such patients, treatment should begin with low doses of the drug.

Heart failure/severe heart failure

In patients with chronic heart failure (functional class IV according to the NYHA classification), treatment with Noliprel® A Bi-forte is not indicated, because Therapy should be started with lower doses of the combination of perindopril and indapamide and under close 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.

Patients with diabetes mellitus

In patients with insulin-dependent diabetes mellitus (risk of spontaneous increase in potassium levels), therapy with the drug Noliprel® A Bi-forte is not advisable, since treatment should begin with minimal doses and be carried out under constant medical supervision.

Glycemic levels should be carefully monitored in patients with diabetes mellitus who have previously received oral hypoglycemic drugs or insulin, namely during the first month of ACE inhibitor therapy (see section "Drug Interactions").

Ethnic differences

Perindopril, like other ACE inhibitors, has a clearly less pronounced antihypertensive effect in patients of the Negroid race compared to representatives of other races. This difference may be due to the fact that black patients with arterial hypertension are more likely to have low renin activity.

Surgery/general anesthesia

The use of ACE inhibitors can lead to arterial hypotension, especially when using anesthetic agents that have antihypertensive effects. Therefore, it is recommended, if possible, to stop taking long-acting ACE inhibitors, incl. perindopril, the day before surgery.

Aortic or mitral valve stenosis/hypertrophic obstructive 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, fulminant liver necrosis may develop, sometimes with death. The mechanism of development of this syndrome is unclear. If jaundice appears or if there is a significant increase in the activity of liver enzymes while taking ACE inhibitors, the patient should stop taking the ACE inhibitor and be under appropriate medical supervision (see section “Side Effects”).

Hyperkalemia

Hyperkalemia may develop during treatment with ACE inhibitors, incl. perindopril. Risk factors for hyperkalemia include renal failure, deterioration of renal function, age over 70 years, diabetes mellitus, certain concomitant conditions, in particular dehydration, acute cardiac decompensation, metabolic acidosis, concomitant use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride ), as well as potassium preparations or potassium-containing substitutes for table salt, the use of other drugs that help increase the content of potassium in the blood plasma (for example, heparins, co-trimoxazole, other ACE inhibitors, ARA II, acetylsalicylic acid at a dose of 3 g/day or more, COX-2 inhibitors and non-selective NSAIDs, immunosuppressants such as cyclosporine or tacrolimus, trimethoprim). 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 lead to serious, sometimes fatal, heart rhythm disturbances. If the 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 section “Drug Interactions”).

Carefully

Systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma, etc.); concomitant use of allopurinol, cytostatics and immunosuppressants, or procainamide (risk of developing neutropenia and agranulocytosis), concomitant therapy with lithium preparations, aliskiren preparations in patients without diabetes mellitus or impaired renal function, ARA II in patients without diabetic nephropathy, gold preparations, NSAIDs, baclofen, corticosteroids, drugs that can cause prolongation of the QT interval, cardiac glycosides, drugs that can cause polymorphic ventricular tachycardia of the "pirouette" type, except for non-antiarrhythmic drugs, suppression of bone marrow hematopoiesis, reduced blood volume (taking diuretics, salt-free diet, vomiting, diarrhea, hemodialysis), coronary artery disease, cerebrovascular diseases, renovascular hypertension, diabetes mellitus, primary hyperaldosteronism, chronic heart failure (II-IV functional class according to the NYHA classification), liver and kidney dysfunction, hyperuricemia (especially accompanied by gout and urate nephrolithiasis), blood pressure lability, old age, desensitization, before the procedure of LDL apheresis, condition after kidney transplantation, anesthesia, aortic valve stenosis/hypertrophic obstructive cardiomyopathy, atherosclerosis, representatives of the Negroid race (less pronounced effect of use), athletes (possible positive reaction during doping control), concomitant therapy with potassium-sparing diuretics, potassium preparations or in patients with elevated plasma potassium levels, hyperkalemia, hyponatremia, aggravated allergic history.

Impact on the ability to drive vehicles and machinery

Both active ingredients, either individually or in combination with indapamide + perindopril, do not affect the ability to drive a car or use other machinery. In some patients, especially at the beginning of therapy or when other antihypertensive drugs are added to therapy, individual reactions associated with a decrease in blood pressure may occur. As a result, the ability to drive a car or operate other machinery may be impaired.

Note!

Description of the drug Noliprel Bi-Forte table. p/o No. 90 on this page is a simplified author’s version of the apteka911 website, created on the basis of the instructions for use.
Before purchasing or using the drug, you should consult your doctor and read the manufacturer's original instructions (attached to each package of the drug). Information about the drug is provided for informational purposes only and should not be used as a guide to self-medication. Only a doctor can decide to prescribe the drug, as well as determine the dose and methods of its use.