Noliprel A Bi-forte, pills 10+2.5mg 30pcs

Composition

Active ingredients:

perindopril arginine 10 mg;

indapamide 2.5 mg;

Auxiliary substances:

lactose monohydrate-142.66 mg;

magnesium stearate-0.9 mg;

maltodextrin-18 mg;

colloidal anhydrous silicon dioxide-0.54 mg;

sodium carboxymethyl starch (type A) – 5.4 mg;

Film shell:

macrogol 6000 — 0.27828 mg; magnesium stearate-0.2622 mg; titanium dioxide (E 171) – 0.83902 mg; glycerol-0.2622 mg; hypromellose-4.3583 mg).

Pharmacological action

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

1. Mechanism of action

Noliprel® A Bi-forte

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

Perindopril

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

– reduces the secretion of aldosterone;

– on the principle of negative feedback increases the activity of renin in the blood plasma;

– with prolonged use reduces OPSS, which is mainly due to the effect on blood vessels in the muscles and kidneys. These effects are not accompanied by retention of sodium or liquid ions or the development of reflex tachycardia.

Perindopril normalizes myocardial function, reducing preload and afterload.

The study of hemodynamic parameters in patients with chronic heart failure (CHF) revealed:

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

– decrease in OPSS;

– increase in cardiac output and increase in cardiac index;

– increase in muscular peripheral blood flow.

Indapamide

Indapamide belongs to the group of sulfonamides, and its pharmacological properties are similar to those of thiazide diuretics. Indapamide inhibits the reabsorption of sodium ions in the cortical segment of the Henle loop, 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 lowering blood pressure.

2. Antihypertensive effect

Noliprel® A Bi-forte

Noliprel ® A Bi-forte has a dose-dependent antihypertensive effect on both dBP and sBP in standing and lying positions. The antihypertensive effect of the drug persists for 24 hours. A stable therapeutic effect develops less than 1 month after the start of therapy and is not accompanied by tachycardia. Discontinuation of treatment does not cause withdrawal symptoms.

Noliprel ® A Bi-forte reduces the degree of left ventricular hypertrophy (LVH), improves the elasticity of the arteries, reduces OPSS, does not affect the metabolism of lipids (total cholesterol, HDL cholesterol, etc. ). LDL, triglycerides).

The effect of using a combination of perindopril and indapamide on GTLF in comparison with enalapril was proved. In patients with arterial hypertension and GTL treated with perindopril erbumin 2 mg (equivalent to 2.5 mg of perindopril arginine)/indapamide 0.625 mg or enalapril at a dose of 10 mg once a day, and with an increase in the dose of perindopril erbumin to 8 mg (equivalent to 10 mg of perindopril arginine) and indapamide to 2.5 mg, or enalapril to 40 mg once a day, there was a more significant decrease in left ventricular mass index (LVMI) in the perindopril/indapamide group compared to the enalapril group. At the same time, the most significant effect on LVMI is observed with the use of perindopril erbumin 8 mg/indapamide 2.5 mg.

There was also a more pronounced antihypertensive effect on the background of combined therapy with perindopril and indapamide compared to enalapril.

Perindopril

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

The antihypertensive effect of the drug reaches a maximum in 4-6 hours after a single oral use and persists for 24 hours. 24 hours after taking the drug, there is a pronounced (about 80%) residual ACE inhibition.

Perindopril has an antihypertensive effect in patients with both low and normal plasma renin activity.

Simultaneous use of thiazide diuretics increases the severity of the antihypertensive effect. In addition, the combination of an ACE inhibitor and a thiazide diuretic also reduces the risk of hypokalemia when taking diuretics.

Indapamide

Antihypertensive effect is manifested when the drug is used in doses that have a minimal diuretic effect.

The antihypertensive effect of indapamide is associated with an improvement in the elastic properties of large arteries, a decrease in OPSS.

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

Pharmacokinetics

Noliprel® A Bi-forte

The combined use of perindopril and indapamide does not change their pharmacokinetic characteristics in comparison with separate use of these drugs.

Perindopril

When taken orally, perindopril is rapidly absorbed. Cmax in blood plasma is reached 1 h after oral use. T_1/2 is 1 h. Perindopril has no pharmacological activity. Approximately 27% of the total amount of oral perindopril enters the bloodstream as the active metabolite, perindoprilat.

In addition to perindoprilat,5 more metabolites are formed that do not have pharmacological activity. _{Cmax of}perindoprilat in blood plasma is reached 3-4 hours after oral use. Food intake slows down the conversion of perindopril to perindoprilate, thus affecting bioavailability. Therefore, the drug should be taken once a day, in the morning, before meals.

There is a linear dependence of the concentration of perindopril in blood plasma on its dose. The_{vd of}unbound perindoprilate is approximately 0.2 l / kg. The association of perindoprilat with plasma proteins, mainly with ACE, depends on the concentration of perindopril and is about 20%.

Perindoprilat is eliminated from the body by the kidneys. Effective T_1/2 unbound fraction is about 17 hours, the equilibrium state is reached within 4 days.

The elimination of perindoprilat is slowed in the elderly, as well as in patients with heart and kidney failure.

The dialysis clearance of perindoprilat is 70 ml / min

. The pharmacokinetics of perindopril are changed in patients with cirrhosis of the liver: its hepatic clearance decreases by 2 times. However, the amount of perindoprilat produced does not decrease, which does not require dose adjustment (see” Dosage and use “and”Special Instructions”).

Indapamide

Indapamide is rapidly and completely absorbed from the gastrointestinal tract.

_cmax of indapamide in blood plasma is observed 1 h after oral use.

Binding to plasma proteins is 79%.

T_1/2 is 14-24 hours (average 18 hours). Repeated use of the drug does not lead to its accumulation in the body. It is mainly excreted by the kidneys (70% of the administered dose) and through the intestine (22%) in the form of inactive metabolites.

The pharmacokinetics of the drug do not change in patients with renal insufficiency.

Indications

Essential hypertension (patients who require therapy with perindopril at a dose of 10 mg and indapamide at a dose of 2.5 mg).

Use during pregnancy and lactation

Pregnancy

Noliprel ® A Bi-forte is contraindicated during pregnancy (see “Contraindications”).

When planning pregnancy or when it occurs while taking the drug, you should immediately stop taking the drug and prescribe another antihypertensive therapy. No relevant controlled studies of ACE inhibitors in pregnant women have been conducted. Limited data available on first-trimester exposure indicate that the drug did not cause fetotoxicity-related malformations.

Noliprel ® A Bi-forte should not be used in the first trimester of pregnancy. Noliprel A Bi-forte is contraindicated in the second and third trimesters of pregnancy.

It is known that prolonged exposure to ACE inhibitors on the fetus in the second and third trimesters of pregnancy can lead to impaired development (decreased renal function, oligohydramnios, slowing of ossification of the skull bones) and the development of complications in the newborn (renal failure, hypotension, hyperkalemia).

Long-term use of thiazide diuretics in the third trimester of pregnancy can cause hypovolemia in the mother and a decrease in uteroplacental blood flow, which leads to fetoplacental ischemia and fetal development delay. In rare cases, newborns develop hypoglycemia and thrombocytopenia while taking diuretics shortly before delivery.

If the patient received Noliprel® A Bi-forte during the second or third trimester of pregnancy, ultrasound of the newborn is recommended to assess the condition of the skull bones and kidney function.

Newborns whose mothers have been treated with ACE inhibitors may experience hypotension, and therefore, newborns should be under close medical supervision.

Breast-feeding period

Noliprel ® A Bi-forte is contraindicated during breastfeeding.

It is not known whether perindopril is excreted in breast milk.

Indapamide is excreted in breast milk. Taking thiazide diuretics causes a decrease in the amount of breast milk or suppression of lactation. The newborn may develop hypersensitivity to sulfonamide derivatives, hypokalemia, and nuclear jaundice.

It is necessary to assess the significance of therapy for the mother and decide whether to stop breastfeeding or stop taking the drug.

Contraindications

Perindopril

• hypersensitivity to perindopril and other ACE inhibitors;
• a history of angioedema (angioedema) associated with taking an ACE inhibitor;
• hereditary/idiopathic angioedema;
• bilateral renal artery stenosis or stenosis of the artery of a single kidney;
• pregnancy;
• breast-feeding period;
• age up to 18 years (efficacy and safety have not been established).

Indapamide

• increased sensitivity to indapamide and other sulphonamides;
• severe hepatic insufficiency (including encephalopathy);
• hypokalemia;
• concomitant use of drugs that can cause arrhythmia type “pirouette” (see “Interaction”);
• pregnancy and breastfeeding (see “pregnancy and breastfeeding”);
• age to 18 years (efficacy and safety not established).

Noliprel® A Bi-Forte

• hypersensitivity auxiliary substances included in the composition of the drug;
• severe renal insufficiency (Cl creatinine
• simultaneous intake with potassium-sparing diuretics, potassium and lithium, and in patients with a high content of potassium ions in the blood plasma;
• the presence of lactase deficiency, galactosemia or syndrome glucose-galactose malabsorption, lactose intolerance;
• concomitant use of drugs that lengthen the QT interval (see “Interaction”);
• due to the lack of sufficient clinical experience, the drug Noliprel® A Bi-Forte should not be used in patients on hemodialysis and in patients with untreated congestive heart failure in the stage of decompensation;
• the age of 18 years (effectiveness and safety not established).

With caution: systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), immunosuppressant therapy (risk of neutropenia, agranulocytosis), bone marrow hematopoiesis suppression, reduced BCC (taking diuretics, salt-free diet, vomiting, diarrhea), IHD, cerebrovascular diseases, renovascular hypertension, diabetes mellitus, chronic heart failure (NYHA functional class IV) hyperuricemia (especially accompanied by gout and urate nephrolithiasis), blood pressure lability, advanced age; hemodialysis using high-flow membranes (for example, AN69®) or desensitization, apheresis LDL, condition after kidney transplantation; aortic valve stenosis/hypertrophic cardiomyopathy.

Side effects

From the circulatory and lymphatic system: very rarely — thrombocytopenia, leukopenia / neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia.

In certain clinical situations (patients after kidney transplantation, patients on hemodialysis), ACE inhibitors can cause anemia (see “Special instructions”).

From the central nervous system: often-paresthesia, headache, dizziness, vertigo; infrequently-sleep disturbance, mood lability; very rarely-confusion; unspecified frequency-fainting.

From the side of the visual organ: often-visual impairment.

From the side of the hearing organ: often-tinnitus.

From the CCC side: infrequently — a marked decrease in Blood pressure, including orthostatic hypotension; very rarely-cardiac arrhythmia, including bradycardia, ventricular tachycardia, atrial fibrillation, as well as angina and myocardial infarction, possibly due to an excessive decrease in blood pressure in high-risk patients (see “Special instructions”); unspecified frequency — arrhythmias of the” pirouette “type (possibly fatal — see” Interaction “and”Special Instructions”).

Respiratory, thoracic and mediastinal disorders: often-against the background of the use of ACE inhibitors, a dry cough may occur, which persists for a long time during taking drugs of this group and disappears after their withdrawal, shortness of breath; infrequently — bronchospasm; very rarely — 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 rarely-pancreatitis; angioedema of the intestine, cholestatic jaundice; unspecified frequency-hepatic encephalopathy in patients with hepatic insufficiency (see “Contraindications” and “Special Instructions”).

From the side of the skin and subcutaneous fat: often-skin rash, pruritus, maculopapular rash; infrequently-angioedema of the face, lips, limbs, tongue mucosa, vocal folds and / or larynx, urticaria (see “Special instructions”), hypersensitivity reactions in patients predisposed to bronchoobstructive and allergic reactions; hemorrhagic vasculitis. Patients with acute systemic lupus erythematosus may worsen the course of the disease. Very rarely — erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome. Photosensitivity reactions have been reported (see “Special instructions”).

Musculoskeletal and connective tissue disorders: often-muscle spasms.

From the urinary system: infrequently — renal failure; very rarely-acute renal failure.

From the side of the reproductive system: infrequently-impotence.

Common disorders and symptoms: often-asthenia; infrequently-increased sweating.

Laboratory parameters: rarely — hypercalcemia; unspecified frequency — increased QT interval on the ECG (see “Interaction” and “Special instructions”), increased uric acid and glucose concentrations in the blood while taking the drug, increased activity of liver enzymes, a slight increase in creatinine concentration in the urine and in the blood plasma, passing after discontinuation of therapy, more often in patients with renal artery stenosis, in the treatment of arterial hypertension with diuretics and in the case of renal failure, hypokalemia, especially significant for patients with risk group (see “Special instructions”); hyperkalemia, often transient; hyponatremia and hypovolemia, leading to dehydration and orthostatic hypotension.

Interaction

Noliprel® A Bi-forte

1. Undesirable combination of drugs

Lithium preparations: with the simultaneous use of lithium preparations and ACE inhibitors, a reversible increase in the content of lithium in blood plasma and associated toxic effects may occur. Additional use of thiazide diuretics may further increase the lithium content and increase the risk of toxicity. Concomitant use of a combination of perindopril and indapamide with lithium preparations is not recommended. In the case of such therapy, regular monitoring of the lithium content in the blood plasma is necessary (see “Special instructions”).

2. A combination of drugs that requires special attention

Baclofen: possible increase in hypotensive effect. Blood pressure and renal function should be monitored, and the dose of antihypertensive drugs should be adjusted if necessary.

NSAIDs, including high doses of acetylsalicylic acid (more than 3 g / day): concomitant use of ACE inhibitors and NSAIDs (acetylsalicylic acid in a dose that has an anti-inflammatory effect, COX-2 inhibitors and non-selective NSAIDs) can lead to a decrease in the antihypertensive effect. Concomitant use of ACE inhibitors and NSAIDs can lead to deterioration of renal function, including the development of acute renal failure and an increase in serum potassium, especially in patients with reduced renal function. Caution should be exercised when prescribing this combination, especially in elderly patients. Patients need to compensate for fluid loss and regularly monitor kidney function, both at the beginning of treatment and during treatment.

3. A combination of tools that requires attention

Tricyclic antidepressants, antipsychotics (neuroleptics): drugs of these classes enhance the antihypertensive effect and increase the risk of orthostatic hypotension (additive effect).

GCS, tetracosactide: reduced antihypertensive effect (fluid retention and sodium ions as a result of corticosteroids).

Other antihypertensive agents: it is possible to increase the antihypertensive effect.

Perindopril

1. Undesirable combination of drugs

Potassium-sparing diuretics (amiloride, spironolactone, triamterene both as monotherapy and as part of combination therapy) and potassium preparations: during therapy with ACE inhibitors, as a rule, the content of potassium in the blood serum remains within normal limits, but hyperkalemia may develop (rarely). Simultaneous use of potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride), potassium preparations and potassium-containing salt substitutes can lead to a significant increase in the content of potassium ions in the blood serum up to a fatal outcome. If the combined use of an ACE inhibitor and the above drugs is necessary (in the case of confirmed hypokalemia), caution should be exercised and regular monitoring of the potassium content in the blood plasma and ECG parameters should be carried out.

2. A combination of drugs that requires special attention

Hypoglycemic drugs for oral use (sulfonylurea derivatives) and insulin:The following effects have been described for captopril and enalapril. ACE inhibitors may increase the hypoglycemic effect of insulin and sulfonylureas in patients with diabetes mellitus. The development of hypoglycemia is very rare (due to an increase in glucose tolerance and a decrease in the need for insulin).

3. Combination of agents requiring attention

Allopurinol, cytostatic and immunosuppressive agents, CORTICOSTEROIDS (with systemic use) and procainamide: concomitant use with ACE inhibitors may be associated with an increased risk of leukopenia.

General anesthesia products: concomitant use of ACE inhibitors and general anaesthetics may lead to an increased antihypertensive effect.

Diuretics (thiazide and loop): the use of diuretics in high doses can lead to hypovolemia, and the addition of perindopril to therapy can lead to arterial hypotension.

Gold preparations: when using ACE inhibitors, including perindopril, in patients receiving intravenous gold preparations (sodium aurothiomalate), a sympathocomplex was described, including facial skin hyperemia, nausea, vomiting, and hypotension.

Indapamide

1. A combination of tools that requires special attention

Drugs that can cause pirouette-type arrhythmia: due to the risk of hypokalemia, caution should be exercised when prescribing indapamide concomitantly with drugs that can cause pirouette-type arrhythmia, for example, antiarrhythmics (quinidine, hydroquinidine, disopyramide, amiodarone, dofetilide, ibutilide, bretilia tosilate, sotalol), some neuroleptics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol); other neuroleptics (pimozide), other drugs such as bepridil, cisapride, difemanyl methylsulfate, intravenous erythromycin, halofantrin, mizolastine, moxifloxacin, pentamidine, sparfloxacin, vincamine iv, methadone, astemizole, terfenadine. Concomitant use with the above drugs should be avoided; the risk of hypokalemia and, if necessary, its correction should be carried out, the QT interval should be monitored.

Medications that may cause hypokalemia: amphotericin B (iv), gluco-and mineralocorticosteroids (with systemic use), tetracosactide, laxatives that stimulate gastrointestinal motility: increased risk of hypokalemia (additive effect). It is necessary to monitor the content of potassium ions in the blood plasma, if necessary — its correction. Special attention should be paid to patients receiving concomitant cardiac glycosides. Laxatives that do not stimulate gastrointestinal motility should be used.

Cardiac Glycosides: hypokalemia increases the toxic effect of cardiac glycosides. When indapamide and cardiac glycosides are used concomitantly, the blood plasma potassium content and ECG parameters should be monitored and, if necessary, therapy should be adjusted.

2. A combination of medications that requires attention

Metformin: functional renal failure, which may occur during the use of diuretics, especially “loop” with simultaneous use of metformin, increases the risk of lactic acidosis. Metformin should not be used if the plasma creatinine concentration exceeds 15 mg / l (135 mmol/l) in men and 12 mg/l (110 mmol/l) for women.

Iodine-containing contrast agents: dehydration of the body while taking diuretics increases the risk of acute renal failure, especially when using high doses of iodine-containing contrast agents. Before using iodine-containing contrast agents, patients need to compensate for fluid loss.

Calcium Salts: with simultaneous use, hypercalcemia may develop due to a decrease in calcium excretion by the kidneys.

Cyclosporine: it is possible to increase the concentration of creatinine in blood plasma without changing the content of cyclosporine, even with a normal content of water and sodium ions.

How to take, course of use and dosage

Inside,1 tablet 1 time a day, preferably in the morning, before meals.

Elderly patients

In elderly patients, creatinine clearance is calculated based on age, body weight, and gender. Elderly patients with normal renal function are prescribed Noliprel ® A Bi-forte 1 tablet 1 time a day, while the degree of blood pressure reduction should be monitored.

Renal failure (see “Special instructions”)

The drug is contraindicated in patients with moderate to severe renal insufficiency (creatinine clearance).

Patients with creatinine clearance equal to or greater than 60 ml/min should be regularly monitored for serum creatinine and potassium concentrations during therapy.

Liver failure

The drug is contraindicated in patients with severe hepatic insufficiency.

In moderate hepatic insufficiency, no dose adjustment is required.

Children and teenagers

Noliprel A Bi-forte should not be prescribed to children and adolescents under 18 years of age due to the lack of data on the effectiveness and safety of the drug in patients of this age group.

Overdose

Symptoms: the most likely symptom of overdose is a marked decrease in blood pressure. Blood pressure, sometimes combined with nausea, vomiting, convulsions, dizziness, drowsiness, confusion and oliguria, which can turn into anuria (as a result of hypovolemia). Electrolyte disturbances (hyponatremia, hypokalemia) may also occur.

Treatment: emergency measures are limited to removing the drug from the body: gastric lavage and / or taking activated carbon, followed by restoring the water-electrolyte balance.

With a significant reduction Blood pressure should be transferred to a supine position with raised legs, if necessary, to correct hypovolemia (for example, intravenous infusion of 0.9% sodium chloride solution). Perindoprilate, the active metabolite of perindopril, can be removed from the body by dialysis.

Special instructions

Noliprel® A Bi-forte

Lithium preparations

Concomitant use of a combination of perindopril and indapamide with lithium preparations is not recommended (see “Interaction”).

Impaired renal function

Noliprel ® A Bi-forte therapy is contraindicated in patients with moderate to severe renal insufficiency (Cl creatinine ® A Bi-forte should be discontinued. In the future, you can resume combination therapy using a low-dose combination of perindopril and indapamide, or use drugs in the monotherapy mode.

Such patients need regular monitoring of serum potassium and creatinine levels-2 weeks after the start of therapy and every 2 months thereafter. Renal failure occurs more frequently in patients with severe chronic heart failure or underlying renal dysfunction, including 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 impaired water-electrolyte balance

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

Severe hypotension may require intravenous use of 0.9% sodium chloride solution.

Transient arterial hypotension is not a contraindication for continuing therapy. After recovery of BCC and BP, you can resume therapy using a low-dose combination of perindopril and indapamide, or use drugs in the monotherapy mode.

Potassium content

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

Auxiliary substances

It should be borne in mind that the excipients of the drug include lactose monohydrate.Noliprel A Bi-forte should not be used in patients with hereditary problems of 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 being 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 the withdrawal of ACE inhibitors, the clinical signs of neutropenia disappear independently.

Perindopril should be used with extreme caution in patients with systemic connective tissue diseases, while taking immunosuppressive agents, allopurinol or procainamide, and when they are used together, especially in patients with initial 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 white blood cells in the blood. Patients should inform the doctor about any signs of infectious diseases (for example, sore throat, fever).

Hypersensitivity/Angioedema (angioedema)

When taking ACE inhibitors, including perindopril, in rare cases, angioedema of the face, limbs, lips, tongue, glottis and/or larynx may develop. If symptoms occur, Noliprel® A Bi-forte should be discontinued immediately and the patient should be monitored until the signs of edema disappear completely. If the swelling affects only the face and lips, then its manifestations usually go away on their own, although antihistamines can be used to treat its symptoms.

Angioedema accompanied by laryngeal edema can be fatal. Swelling of the tongue, glottis, or larynx can lead to airway obstruction. If such symptoms occur, epinephrine (epinephrine) should be immediately administered subcutaneously at a dilution of 1: 1000 (0.3 or 0.5 ml) and / or airway patency should be ensured.

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

In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. At the same time, patients have 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 established by computed tomography of the abdominal region, ultrasound, or at the time of surgery. Symptoms disappear after discontinuation of ACE inhibitors. In patients with abdominal pain treated with ACE inhibitors, the differential diagnosis should take into account the possibility of developing angioedema of the intestine.

Anaphylactoid reactions during desensitization

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

Anaphylactoid reactions during LDL apheresis

In rare cases, patients receiving ACE inhibitors may develop life-threatening anaphylactoid reactions 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-flow membranes (for example, AN69®). Therefore, it is desirable to use a different type of membrane or use a hypotensive 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 salt substitutes is not recommended (see “Interaction”).

Cough

During ACE inhibitor therapy, a dry cough may occur. Cough persists for a long time against the background of taking drugs of this group and disappears after their cancellation. If a patient has a dry cough, you should be aware of the possible association 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 18 years of age due to the lack of data on the efficacy and safety of monopreparations or combination therapy in patients of this age group.

Risk of hypotension and / or renal failure (in patients with chronic heart failure, impaired water-electrolyte balance, etc. )

In some pathological conditions, significant activation of the RAAS may occur, especially with severe hypovolemia and a decrease in plasma electrolytes (against the background of a salt-free diet or long-term use of diuretics), in patients with initially low blood pressure, renal artery stenosis (including bilateral), chronic 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 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 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 decrease in blood pressure, especially in the case of a decrease in BCC and loss of electrolytes. Such measures can avoid a sharp decrease in blood pressure.

Atherosclerosis

The risk of arterial hypotension exists in all patients, but special care should be taken when using the drug in patients with CHD and cerebral circulatory insufficiency. In such patients, treatment should be initiated with a low-dose combination of perindopril arginine and indapamide.

Patients with renovascular hypertension

The method of treating renovascular hypertension is revascularization. However, the use of ACE inhibitors has a beneficial effect in patients who are waiting for surgery, and in the case when it is impossible to perform surgery.

In patients with diagnosed or suspected renal artery stenosis, treatment should be initiated with a lower dose 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 (NYHA functional Class IV) and type 1 diabetes mellitus (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 CHD should not stop taking beta-blockers: the combination of perindopril and indapamide should be used together with beta-blockers.

Patients with diabetes mellitus

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

Ethnic differences

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

Surgical intervention/General anesthesia

The use of ACE inhibitors in patients undergoing surgery with general anesthesia may lead to a pronounced decrease in blood pressure, especially when using general anesthesia agents that have an antihypertensive 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 used with caution in patients with left ventricular outlet obstruction and mitral stenosis.

Liver failure

In rare cases, cholestatic jaundice occurs while taking ACE inhibitors. With the progression of this syndrome, fulminant liver necrosis develops, sometimes with a fatal outcome. 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, Noliprel® A Bi-forte should be discontinued (see “Side effects”).

Anemia

Anemia can develop in patients after kidney transplantation or in patients undergoing hemodialysis. At the same time, the decrease in hemoglobin is greater, the higher its initial indicator was. 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, impaired renal function, advanced 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), as well as potassium preparations or potassium-containing salt substitutes, as well as the use of other agents that increase the content of potassium ions in blood plasma (for example, heparin) (especially in patients with reduced renal function). Hyperkalemia can lead to serious, sometimes fatal, cardiac arrhythmias. 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 impaired liver function, taking thiazide and thiazide-like diuretics can lead to the development of hepatic encephalopathy. In this case, Noliprel A Bi-forte should be discontinued immediately.

Photosensitivity

Photosensitivity reactions have been reported with 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-electrolyte balance

The content of sodium ions in the 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 ions is indicated in elderly patients (see “Side effects” and “Overdose”).

The content of potassium ions in the blood plasma. Therapy with thiazide and thiazide-like diuretics is associated with the risk of hypokalemia. Hypokalemia (less than 3.4 mmol) should be avoided. /k) in the following categories of high-risk patients: elderly patients, emaciated patients or receiving concomitant drug therapy, patients with cirrhosis of the liver, peripheral edema or ascites, coronary heart disease, chronic heart failure. Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of arrhythmia.

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

Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, especially pirouette-type 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 the potassium ion content should be carried out within the first week after the start of therapy.

If hypokalemia is detected, appropriate treatment should be prescribed.

The content of calcium ions in the 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.

Concentration of glucose in blood plasma

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

Uric acid

In patients with an increased concentration of uric acid in the blood plasma against the background of therapy, the frequency of gout attacks may increase.

Diuretics and renal function

Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (plasma creatinine concentrations in adult patients below 25 mg / l or 220 mmol/l). In elderly patients, Creatinine clearance is calculated based on age, body weight, and gender.

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

Athletes

Indapamide can give a positive reaction during doping control.

Influence on the ability to drive a car or perform work that requires an increased rate of physical and mental reactions. The action of the drugs included in Noliprel® A Bi-forte does not lead to a violation 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 agents are added to the therapy. In this case, the ability to drive vehicles or perform work that requires an increased rate of physical and mental reactions may be reduced.

Composition

Tablet Form of production

Storage conditions

No special storage conditions are required

Shelf life

3 years

Active ingredient

Indapamide, Perindopril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension