Noliprel A, pills 2.5+0.625mg 30pcs

Composition

1 tablet contains:

• the active ingredients of perindopril arginine are 2.5 mg, which corresponds to 1.6975 mg of perindopril and 0.625 mg of indapamide.
• :
• lactose monohydrate 74.455 mg,
• magnesium stearate 0.45 mg,
• maltodextrin 9 mg,
• colloidal anhydrous silicon dioxide 0.27 mg,
• sodium carboxymethyl starch (type A) 2.7 mg.
• :
• macrogol 6000 0.087 mg, premix for white film coating SEPIFILM 37781 RBC (glycerol 4.5%, hypromellose 74.8%, macrogol 6000 1.8%, magnesium stearate 4.5%, titanium dioxide (E 171) 14.4%) 2.913 mg

Pharmacological action

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

1. Mechanism of action

Noliprel® A

The combination of perindopril 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 and fluid ions or the development of reflex tachycardia.

Perindopril normalizes myocardial function, reducing preload and afterload.

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

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

– decrease in OPSS;

– increase in cardiac output;

– 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 release 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

Noliprel ® A has a dose-dependent antihypertensive effect on both dBP and sBP in both standing and lying positions. The antihypertensive effect 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 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, LDL cholesterol, triglycerides).

The effect of using a combination of perindopril and indapamide on GTLF in comparison with enalapril was proved. In patients with 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, a more significant decrease in body mass index was observed 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.

In patients with diabetes mellitus type 2 (average age 66 years, body mass index of 28 kg/m2, glycated hemoglobin (HbA1c) 7.5 per cent, AD — 145/81 mm Hg. calendar) studied the effect of a fixed combination of perindopril/indapamide on the major micro – and macrovascular complications in addition to standard therapy, glycemic control, and the strategy of intensive glycemic control (GCI) (target HbA1c

in 83% of patients had hypertension,32 and 10% of macro – and microvascular complications,27% — microalbuminuria. The majority of patients at the time of inclusion in the study received hypoglycemic therapy,90% of patients received oral hypoglycemic agents (47% of patients received monotherapy,46% received two — drug therapy, and 7% received three — drug therapy).1% of patients received insulin therapy,9% – only diet therapy. 72% of patients received sulfonylureas and 61% received metformin. As concomitant therapy,75% of patients received antihypertensive agents,35% of patients received lipid-lowering agents (mainly HMG-CoA reductase inhibitors (statins) — 28%), acetylsalicylic acid as an antiplatelet agent and other antiplatelet agents (47%).

After a 6-week introductory period, during which patients received perindopril/ indapamide therapy, they were assigned to the standard glycemic control group or to the IGC group (Diabeton® MV with the possibility of increasing the dose to a maximum of 120 mg/day or adding another hypoglycemic agent).

In the IGC group (mean follow – up — 4.8 years, mean HbA1c — 6.5%), compared with the standard control group (mean HbA1c – 7.3%), a significant 10% reduction in the relative risk of combined incidence of macro-and microvascular complications was shown.

The advantage was achieved by significantly reducing the relative risk of major microvascular complications by 14%, the occurrence and progression of nephropathy by 21%, microalbuminuria by 9%, macroalbuminuria by 30%, and the development of kidney complications by 11%.

The benefits of antihypertensive therapy did not depend on the benefits achieved with IGC.

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, HDL; carbohydrate metabolism (including in patients with concomitant diabetes mellitus).

Pharmacokinetics

The combination 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. Bioavailability is 65-70%.

Approximately 20% of the total amount of absorbed perindopril is converted to perindoprilate, the active metabolite. Taking the drug with meals is accompanied by a decrease in the metabolism of perindopril to perindoprilat (this effect has no significant clinical significance).

_{Cmax of}perindoprilat in blood plasma is reached 3-4 hours after oral use.

The binding to plasma proteins is less than 30% and depends on the concentration of perindopril in the blood.

Dissociation of ACE-associated perindoprilate is slowed. As a result, the effective T_1/2is 25 hours. Repeated use of perindopril does not lead to its accumulation, and T_1/2of perindoprilat during repeated use corresponds to the period of its activity, so the equilibrium state is reached after 4 days.

Perindoprilat is eliminated from the body by the kidneys. T_1/2 of the metabolite is 3-5 hours.

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, so no dose adjustment is required.

Perindopril passes through the placenta.

Indapamide

Indapamide is rapidly and completely absorbed from the gastrointestinal tract.

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

Binding to plasma proteins is 79%.

T_1/2 is 14-24 hours (average 19 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 with arterial hypertension and type 2 diabetes mellitus to reduce the risk of microvascular complications (from the kidneys) and macrovascular complications from cardiovascular diseases.

Use during pregnancy and lactation

The drug is contraindicated during pregnancy.

When planning pregnancy or when it occurs while taking Noliprel® A, the drug should be immediately discontinued and another antihypertensive therapy should be prescribed.

Noliprel ® A should not be used in the first trimester of pregnancy.

No relevant controlled studies of ACE inhibitors in pregnant women have been conducted. Limited data available on the effects of ACE inhibitors in the first trimester of pregnancy indicate that taking ACE inhibitors did not lead to fetal malformations associated with fetotoxicity, but the fetotoxic effect of the drug cannot be completely excluded.

Noliprel ® A is contraindicated in the second and third trimester of pregnancy (see “Contraindications”).

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 during the second or third trimester of pregnancy, it is recommended to perform an ultrasound of the newborn to assess the condition of the skull and kidney function.

Newborns whose mothers have been treated with ACE inhibitors may experience hypotension, and therefore newborns should be closely monitored.

Lactation period

Noliprel ® A is contraindicated during lactation.

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.

Since the use of perindopril and indapamide during lactation can cause severe complications in an infant, it is necessary to assess the significance of therapy for the mother and decide whether to stop breastfeeding or taking the drug.

Contraindications

• hypersensitivity to perindopril and other ACE inhibitors, indapamide, to other sulfonamides and to other ancillary components included in the composition of the drug;
• a history of angioedema (including in patients receiving other ACE inhibitors);
• hereditary/idiopathic angioneurotic edema, hypokalemia, renal insufficiency (Cl creatinine less than 30 ml/min);
• stenosis of the artery to a solitary kidney, bilateral renal artery stenosis;
• severe hepatic insufficiency (including encephalopathy);
• simultaneous reception of drugs, lengthening the interval QT interval;
• concomitant use with antiarrhythmic drugs that can cause arrhythmia of the “pirouette”type;
• pregnancy;
• breast-feeding period.

It is not recommended to take the drug together with potassium-sparing diuretics, potassium and lithium preparations and prescribe it to patients with increased potassium content in blood plasma.

Due to the lack of sufficient clinical experience, Noliprel® A should not be used in patients undergoing hemodialysis, as well as in patients with untreated decompensated heart failure.

With caution: systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), immunosuppressant therapy (risk of neutropenia, agranulocytosis), suppression of bone marrow hematopoiesis, reduced BCC (taking diuretics, salt-free diet, vomiting, diarrhea, hemodialysis), angina pectoris, cerebrovascular diseases, renovascular hypertension, diabetes mellitus, chronic heart failure (IV NYHA stage), hyperuricemia (especially accompanied by gout and urate nephrolithiasis), blood pressure lability, advanced age; hemodialysis using high-flow membranes or desensitization, before the LDL apheresis procedure; condition after kidney transplantation; aortic valve stenosis/hypertrophic cardiomyopathy; presence of lactase deficiency, galactosemia or glucose-galactose malabsorption syndrome; age up to 18 years (efficacy and safety have not been established).

Side effects

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

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, asthenia, 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: often — a marked decrease Blood pressure, including orthostatic hypotension; very rarely – cardiac arrhythmias, 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 — arrhythmia of the” pirouette “type (possibly fatal — see”Interaction”).

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, taste perception disorders, decreased appetite, dyspepsia, constipation, diarrhea; very rarely-angioedema of the intestine, cholestatic jaundice; pancreatitis; unspecified frequency-hepatic encephalopathy in patients with hepatic insufficiency (see “Contraindications”, “Special instructions”), hepatitis.

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; purpura, in 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: hyperkalemia, more often — transient; slight increase in the concentration of creatinine in the urine and 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; rarely — hypercalcemia; unspecified frequency — increased QT interval on the ECG (see “Special instructions”), increased uric acid and glucose concentrations in the blood, increased activity of liver enzymes, hypokalemia, especially significant for patients with hyponatremia and hypovolemia leading to dehydration and orthostatic hypotension (see “Special instructions”). Simultaneous hypochloremia can lead to metabolic alkalosis of a compensatory nature (the probability and severity of this effect is low).

Side effects reported in clinical trials

The side effects reported in the ADVANCE study are consistent with the previously established safety profile of the combination of perindopril and indapamide. Serious adverse events were observed in some patients in the study groups: hyperkalemia (0.1%), acute renal failure (0.1%), hypotension (0.1%) and cough (0.1%).

Angioedema was observed in 3 patients in the perindopril/indapamide group (compared to 2 in the placebo group).

Interaction

1. Combinations not recommended for use

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

2. Drugs that require special attention and caution when combined with them

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): The use of NSAIDs may reduce the diuretic, natriuretic and antihypertensive effects. With significant fluid loss, acute renal failure may develop (due to a decrease in the glomerular filtration rate). Before starting treatment with the drug, it is necessary to replenish the loss of fluid and regularly monitor kidney function at the beginning of treatment.

3. A combination of medications that requires attention

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

Corticosteroids, 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. Combinations not recommended for use

Potassium-sparing diuretics (amiloride, spironolactone, triamterene) and potassium preparations:ACE inhibitors reduce the diuretic-induced loss of potassium in the kidneys. Potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride), potassium preparations and potassium-containing food salt substitutes can lead to a significant increase in the concentration of potassium in the blood serum up to a fatal outcome. If simultaneous 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 agents 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 drugs requiring attention

Allopurinol, cytostatic and immunosuppressive agents, corticosteroids (for 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 preparation (sodium aurothiomalate), a symptom complex was described, including: facial skin hyperemia, nausea, vomiting, arterial hypotension.

Indapamide

1. A combination of drugs that requires special attention

Drugs that can cause pirouette-type arrhythmia: due to the risk of hypokalemia, caution should be exercised when using indapamide concomitantly with drugs that can cause pirouette-type arrhythmia, for example, antiarrhythmic agents (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, erythromycin (iv), 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.

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

2. A combination of medications that requires attention

Metformin: functional renal failure, which may occur during the use of diuretics, especially loop diuretics, 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 the excretion of calcium ions by the kidneys.

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

How to take, course of use and dosage

Inside, preferably in the morning, before meals.

Essential hypertension

Take 1 tablet of Noliprel® A once a day.

If possible, start taking the drug with the selection of doses of single-component drugs. If clinically necessary, the possibility of prescribing combination therapy with Noliprel® A immediately after monotherapy may be considered.

Patients with arterial hypertension and type 2 diabetes mellitus to reduce the risk of microvascular complications (from the kidneys) and macrovascular complications from cardiovascular diseases

Take 1 tablet of Noliprel® A once a day. After 3 months of therapy, if well tolerated, it is possible to increase the dose to 2 tablets of Noliprel® A 1 time a day (or 1 tablet of Noliprel® A forte 1 time a day).

Elderly patients

Treatment with the drug should be prescribed after monitoring of renal function and blood pressure.

Kidney failure

The drug is contraindicated in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min).

For patients with moderate renal insufficiency (creatinine clearance 30-60 ml/min), it is recommended to start therapy with the necessary doses of drugs (in the form of monotherapy) included in Noliprel® A.

No dose adjustment is required in patients with creatinine clearance equal to or greater than 60 ml / min. During therapy, regular monitoring of the level of creatinine and potassium in the blood plasma is necessary.

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 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 prescribing activated carbon, followed by restoring the water-electrolyte balance.

With a significant reduction The patient should be placed in a supine position with raised legs. If necessary, correct hypovolemia (for example, an 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

The use of Noliprel ® A 2.5 mg + 0.625 mg, containing a low dose of indapamide and perindopril arginine, is not accompanied by a significant reduction in the frequency of side effects, with the exception of hypokalemia, compared with perindopril and indapamide in the lowest permitted doses (see “Side effects”). At the beginning of therapy with two antihypertensive drugs that the patient has not received before, an increased risk of idiosyncrasy cannot be excluded. Careful monitoring of the patient reduces this risk to a minimum.

Impaired renal function

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

Arterial hypotension and impaired water-electrolyte balance

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

With severe arterial hypotension, an intravenous injection of 0.9% sodium chloride solution may be required.

Transient arterial hypotension is not a contraindication for continuing therapy. After recovery of BCC and blood pressure, you can resume therapy using low doses of drugs, or use drugs in the monotherapy mode.

Potassium level

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 combined use of an antihypertensive drug and a diuretic, regular monitoring of the level of potassium 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 should not be used in patients with hereditary problems of galactose intolerance, lactase deficiency, and glucose-galactose malabsorption.

Lithium preparations

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

Perindopril

Neutropenia / agranulocytosis

The risk of developing neutropenia while taking ACE inhibitors is dose-dependent and depends on the drug 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, signs of neutropenia go away on their own.

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

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 appear, perindopril 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, immediately administer subcutaneous epinephrine (epinephrine) in a dilution of 1: 1000 (0.3 or 0.5 ml) and / or ensure airway patency.

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.

Anaphylactoid reactions during desensitization

There are isolated reports of the development of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with hymenopteran venom (bees, wasps). ACE inhibitors should be used with caution in allergic patients 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 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 or hemodialysis using high-flow membranes. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be temporarily discontinued at least 24 hours before the apheresis procedure.

Cough

During 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 iatrogenic nature of this symptom. If the attending physician believes that therapy with an ACE inhibitor is necessary for the patient, the drug may be continued.

Children and teenagers

The drug 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 perindopril as monotherapy or as part of combination therapy in patients of this age group.

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

In some pathological conditions, significant activation of the PAAC system may occur, especially with severe hypovolemia and a decrease in plasma electrolyte levels (against the background of a salt-free diet or prolonged use of diuretics), in patients with initially low blood pressure, with bilateral renal artery stenosis or with stenosis of the artery of a single kidney, chronic heart failure or cirrhosis of the liver with edema and ascites.

The use of an ACE inhibitor causes blockade of this system and therefore may be accompanied by a sharp decrease in blood pressure and/or an increase in the level 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 and during other periods of therapy. In such cases, when resuming therapy, it is recommended to use the drug at a lower dose and then gradually increase the dose.

Elderly patients

Before starting the drug, it is necessary to evaluate the functional activity of the kidneys and the concentration of potassium in the blood plasma. At the beginning of therapy, the dose of the drug is selected, taking into account the degree of reduction in blood pressure, especially in the case of dehydration and loss of electrolytes. Such measures 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 low doses.

Patients with renovascular hypertension

The method of treating renovascular hypertension is revascularization. Nevertheless, the use of ACE inhibitors has a beneficial effect in this category of patients, both waiting for surgery and in the case when surgical intervention is impossible.

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

Other risk groups

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

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

Anemia

Anemia can develop in patients after kidney transplantation or in people on hemodialysis. At the same time, the decrease in the concentration of 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.

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

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 a hypotensive effect.

It is recommended to stop taking long-acting ACE inhibitors, including perindopril, one day before surgery. The anaesthetist should be advised that the patient is taking ACE inhibitors.

Aortic stenosis/hypertrophic cardiomyopathy

ACE inhibitors should be used with caution in patients with left ventricular exit tract obstruction.

Liver failure

In rare cases, cholestatic jaundice occurs while taking ACE inhibitors. With the progression of this syndrome, rapid development of liver necrosis is possible, sometimes with a fatal outcome. The mechanism of development of this syndrome is unclear. If jaundice occurs or there is a significant increase in the activity of liver enzymes while taking ACE inhibitors, you should stop taking the drug and consult a doctor (see “Side effects”).

Indapamide

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

Water-electrolyte balance

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 patients with cirrhosis of the liver and the elderly (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 patients from the high-risk group: elderly people, emaciated patients or receiving concomitant drug therapy, patients with cirrhosis of the liver, peripheral edema or ascites, coronary heart disease, heart failure. Hypokalemia increases the toxic effect of cardiac glycosides and increases the risk of arrhythmias.

The high-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, more regular monitoring of the content of potassium ions in the blood plasma is necessary. The first measurement of the potassium ion concentration 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 concentration of calcium 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.

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

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

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

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.

Photosensitivity

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

Athletes

Indapamide can give a positive reaction during doping control.

Influence on the ability to drive a car or mechanical devices. The effect of the substances that make up Noliprel® A does not lead to a violation of psychomotor reactions. However, some people may develop different individual reactions in response to a decrease in blood pressure, especially at the beginning of therapy or when other antihypertensive drugs are added to the therapy. In this case, the ability to drive a car or other mechanisms may be reduced.

Form of production

Tablets

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