What are the dosages of Noliprel a forte? A unique drug for the treatment of hypertension Noliprel Forte. Contraindications for use

Tablets - 1 tablet:

• active substances: perindopril arginine 5 mg, which corresponds to 3.395 mg of perindopril and indapamide 1.25 mg;
• excipients: lactose monohydrate 71.33 mg, magnesium stearate 0.45 mg, maltodextrin 9 mg, colloidal anhydrous silicon dioxide 0.27 mg, sodium carboxymethyl starch (type A) 2.7 mg;
• film shell: macrogol-6000 0.087 mg, premix for white film shell 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.

Film-coated tablets, 5 mg + 1.25 mg.

1 bottle (14 and/or 30 tablets each) or 3 bottles (30 tablets each) with instructions for medical use in a cardboard pack with first opening control.

During packaging (packing)/production at the Russian enterprise Serdix LLC:

14 or 30 tablets in a polypropylene bottle equipped with a dispenser and a stopper containing a moisture-absorbing gel.

1 bottle (14 and/or 30 tablets each) with instructions for medical use and a cardboard pack with first opening control.

Packaging for hospitals:

30 tablets in a polypropylene bottle equipped with a dispenser and a stopper containing a moisture-absorbing gel.

3 bottles of 30 tablets each with instructions for medical use in a cardboard pack with first opening control.

30 bottles of 30 tablets each in a cardboard tray for bottles with instructions for medical use in a cardboard box with first opening control.

Description of the dosage form

Oblong, film-coated tablets, white.

pharmachologic effect

Combination antihypertensive drug (diuretic + ACE inhibitor).

Pharmacokinetics

The combination of perindopril and indapamide does not change their pharmacokinetic characteristics compared to taking these drugs separately.

Perindopril

When taken orally, perindopril is rapidly absorbed. Bioavailability is 65-70%. Approximately 20% of the total amount of absorbed perindopril is converted to perindoprilat, the active metabolite. Taking the drug with food is accompanied by a decrease in the metabolism of perindopril to perindoprilat (this effect does not have significant clinical significance).

The maximum concentration of perindoprilate in the blood plasma is achieved 3-4 hours after oral administration. The binding to plasma proteins is less than 30% and depends on the concentration of perindopril in the blood. The dissociation of perindoprilate associated with ACE is slowed down. As a result, the “effective” half-life (T1/2) is 25 hours. Repeated administration of perindopril does not lead to its accumulation, and T1/2 of perindoprilat upon repeated administration corresponds to the period of its activity, thus, an equilibrium state is achieved after 4 days.

Perindoprilat is excreted from the body by the kidneys. T1/2 of the metabolite is 3-5 hours.

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

The dialysis clearance of perindoprilate is 70 ml/min.

The pharmacokinetics of perindopril is changed in patients with liver cirrhosis: its hepatic clearance is reduced by 2 times. However, the amount of perindoprilate formed does not decrease, so no change in the dose of the drug is required.

Perindopril crosses the placenta.

Indapamide

Indapamide is quickly and completely absorbed from the gastrointestinal tract. The maximum concentration of the drug in the blood plasma is observed 1 hour after oral administration.

Communication with blood plasma proteins - 79%.

T1/2 is 14-24 hours (average 19 hours). Repeated administration of the drug does not lead to its accumulation in the body. It is excreted mainly by the kidneys (70% of the administered dose) and through the intestines (22%) in the form of inactive metabolites. The pharmacokinetics of the drug does not change in patients with renal failure.

Pharmacodynamics

Noliprel® A forte is a combination drug containing perindopril arginine and indapamide.

The pharmacological properties of the drug Noliprel® A forte combine the individual properties of each of the components.

Mechanism of action

Noliprel® A forte

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 (angiotensin-converting enzyme (ACE) inhibitor). ACE, or kininase II, is an exopeptidase that carries out both the conversion of angiotensin I into the vasoconstrictor substance angiotensin II, and the destruction of bradykinin, which has a vasodilatory effect, into an inactive heptapeptide.

As a result, perindopril:

• reduces the secretion of aldosterone;
• according to the principle of negative feedback, it increases the activity of renin in the blood plasma;
• with long-term use, it reduces total peripheral vascular resistance (TPVR), which is mainly due to the effect on the vessels in the muscles and kidneys. These effects are not accompanied by sodium and fluid retention or the development of reflex tachycardia. Perindopril normalizes myocardial function, reducing preload and afterload.

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

• decreased filling pressure in the left and right ventricles of the heart; decrease in OPSS;
• increased cardiac output;
• increased muscle peripheral blood flow.

Indapamide

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

Antihypertensive effect

Noliprel® A forte

Noliprel® A forte has a dose-dependent antihypertensive effect on both diastolic and systolic blood pressure in both the standing and lying positions.

The antihypertensive effect persists for 24 hours. A stable therapeutic effect develops in less than 1 month from the start of therapy and is not accompanied by tachycardia. Stopping treatment does not cause withdrawal syndrome.

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

The effect of using a combination of perindopril and indapamide on LVG in comparison with enalapril has been proven. In patients with arterial hypertension and LVH who were treated with perindopril erbumine 2 mg (equivalent to 2.5 mg perindopril arginine)/indapamide 0.625 mg or enalapril 10 mg once daily, and with an increase in the dose of perindopril erbumine to 8 mg (equivalent to 10 mg perindopril arginine) and indapamide up to 2.5 mg, or enalapril up to 40 mg once daily, a more significant decrease in left ventricular mass index (LVMI) was noted in the perindopril/indapamide group compared with the enalapril group. In this case, the most significant effect on LVMI was observed with the use of perindopril erbumine 8 mg/indapamide 2.5 mg.

A more pronounced antihypertensive effect was also noted during combination therapy with perindopril and indapamide compared to enalapril.

In patients with type 2 diabetes (mean age 66 years, body mass index 28 kg/m2, glycosylated hemoglobin (HbAlc) 7.5%, blood pressure 145/81 mm Hg), the effect of a fixed combination of perindopril/indapamide was studied on major micro- and macrovascular complications in addition to both standard glycemic control therapy and intensive glycemic control (IGC) strategies (targeted HbAlc

83% of patients had arterial hypertension, 32% and 10% had macro- and microvascular complications, and 27% had microalbuminuria. The majority of patients at the time of inclusion in the study were receiving hypoglycemic therapy, 90% of patients were receiving oral hypoglycemic agents (47% of patients in monotherapy, 46% in two-drug therapy, 7% in three-drug therapy). 1% of patients received insulin therapy, 9% received diet therapy only.

Sulfonylurea derivatives were taken by 72% of patients, metformin by 61%. As concomitant therapy, 75% of patients received antihypertensive drugs, 35% of patients received lipid-lowering drugs (mainly HMG-CoA reductase inhibitors (statins) - 28%), acetylsalicylic acid as an antiplatelet agent and other antiplatelet drugs (47%).

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

The IGC group (mean follow-up 4.8 years, mean HbAlc 6.5%) compared with the standard control group (mean HbAlc 7.3%) showed a significant 10% reduction in the relative risk of the combined incidence of macro- and microvascular complications. The benefit was achieved due to a significant reduction in 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 renal complications by 11%.

The benefits of antihypertensive therapy were independent of the benefits achieved with IGCs.

Perindopril

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

The antihypertensive effect of the drug reaches its maximum 4-6 hours after a single oral dose and persists for 24 hours. 24 hours after taking the drug, pronounced (about 80%) residual ACE inhibition is observed. Perindopril has an antihypertensive effect in patients with both low and normal plasma renin activity.

The simultaneous administration 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 while taking diuretics.

Indapamide

The antihypertensive effect occurs 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 and a decrease in peripheral vascular resistance.

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

Indications for use Noliprel a forte

• essential arterial hypertension;
• patients with arterial hypertension and type 2 diabetes mellitus to reduce the risk of developing microvascular complications (from the kidneys) and macrovascular complications from cardiovascular diseases.

Contraindications to the use of Noliprel a forte

• hypersensitivity to perindopril and other ACE inhibitors, indapamide, other sulfonamides, as well as to other auxiliary components included in the drug;
• history of angioedema (including while taking other ACE inhibitors);
• hereditary/idiopathic angioedema;
• hypokalemia;
• severe renal failure (creatinine Cl less than 30 ml/min);
• stenosis of the artery of a single kidney;
• bilateral renal artery stenosis;
• severe liver failure (including with encephalopathy);
• simultaneous use of drugs that prolong the QT interval;
• simultaneous use with antiarrhythmic drugs that can cause pirouette-type arrhythmia;
• pregnancy;
• breastfeeding period.

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

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

Noliprel a forte Use during pregnancy and children

The drug is contraindicated during pregnancy.

If you are planning pregnancy or if it occurs while taking Noliprel® A forte, you should immediately stop taking the drug and prescribe other antihypertensive therapy.

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

There have been no adequate controlled studies on the use of ACE inhibitors in pregnant women. The limited available data on the effects of ACE inhibitors in the first trimester of pregnancy indicate that taking ACE inhibitors did not lead to fetotoxicity-related fetal malformations, but fetotoxic effects of the drug cannot be completely excluded.

Noliprel® A forte is contraindicated in the 2nd and 3rd trimester of pregnancy.

It is known that long-term exposure of the fetus to ACE inhibitors in the second and third trimesters of pregnancy can lead to disruption of its development (decreased renal function, oligohydramnios, delayed ossification of the skull bones) and the development of complications in the newborn (renal failure, arterial 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 growth retardation. In rare cases, while taking diuretics shortly before birth, newborns develop hypoglycemia and thrombocytopenia.

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

In newborns whose mothers received therapy with ACE inhibitors, arterial hypotension may be observed, and therefore newborns should be under close medical supervision.

Lactation period

Noliprel® A forte 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 serious complications in an infant, it is necessary to evaluate the significance of therapy for the mother and decide whether to stop breastfeeding or stop taking the drug.

Noliprel a forte Side effects

Perindopril has an inhibitory effect on the RAAS and reduces potassium loss by the kidneys while taking indapamide. In 4% of patients, while using the drug Noliprel® A forte, hypokalemia develops (potassium level less than 3.4 mmol/l).

The frequency of adverse reactions that may occur during therapy is given in the following gradation: very often (>1/10); often (>1/100, 1/1000, 1/10000,

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

Anemia: In certain clinical situations (kidney transplant patients, hemodialysis patients), ACE inhibitors may cause anemia.

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

From the organ of hearing: often - tinnitus.

From the cardiovascular system: often - a pronounced decrease in blood pressure, incl. orthostatic hypotension; very rarely - heart rhythm disturbances, incl. bradycardia, ventricular tachycardia, atrial fibrillation, as well as angina pectoris and myocardial infarction, possibly due to an excessive decrease in blood pressure in high-risk patients; unspecified frequency - pirouette-type arrhythmias.

From the respiratory system, chest organs and mediastinum: often - during the use of ACE inhibitors, a dry cough may occur, which persists for a long time while 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 - angioedema of the intestine, cholestatic jaundice, pancreatitis; unspecified frequency - hepatic encephalopathy in patients with liver failure, hepatitis.

From the skin and subcutaneous fat: often - skin rash, itching, maculopapular rash; uncommon - angioedema of the face, lips, extremities, mucous membrane of the tongue, vocal folds and/or larynx; hives; hypersensitivity reactions in patients predisposed to broncho-obstructive and allergic reactions; purpura, in patients with an acute form of systemic lupus erythematosus, the course of the disease may worsen; very rarely - erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome. Cases of photosensitivity reactions have been reported.

From the musculoskeletal system and connective tissue: often - muscle spasms.

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

From the reproductive system: infrequently - impotence.

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

Laboratory indicators: hyperkalemia, more often transient; a slight increase in the concentration of creatinine in the urine and in the blood plasma, which occurs after discontinuation of therapy, more often in patients with renal artery stenosis, when treating hypertension with diuretics and in cases of renal failure; rarely - hypercalcemia; unspecified frequency - an increase in the QT interval on the ECG, an increase in the concentration of uric acid and glucose in the blood, an increase in the activity of liver enzymes, hypokalemia, especially significant for patients at risk, hyponatremia and hypovolemia, leading to dehydration and orthostatic hypotension. Simultaneous hypochloremia can lead to compensatory metabolic alkalosis (the likelihood and severity of this effect is low).

Drug interactions

Lithium preparations: with simultaneous use of lithium preparations and ACE inhibitors, a reversible increase in the concentration of lithium in the blood plasma and associated toxic effects may occur. Additional administration of thiazide diuretics may further increase lithium concentrations and increase the risk of toxicity. The simultaneous 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 section "Special Instructions").

Drugs that require special attention and caution when combined with them

Baclofen: may enhance the hypotensive effect. Blood pressure and renal function should be monitored and, if necessary, dose adjustment of antihypertensive drugs is required.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including high doses of acetylsalicylic acid (more than 3 g/day): the administration of NSAIDs may lead to a decrease in diuretic, natriuretic and antihypertensive effects. With significant fluid loss, acute renal failure may develop (due to a decrease in glomerular filtration rate). Before starting treatment with the drug, it is necessary to replace fluid loss and regularly monitor kidney function at the beginning of treatment.

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

Corticosteroids, tetracosactide: decreased antihypertensive effect (fluid and sodium ion retention as a result of the action of corticosteroids).

Other antihypertensive drugs: the antihypertensive effect may be enhanced.

Potassium-sparing diuretics (amiloride, spironolactone, triamterene) and potassium supplements: ACE inhibitors reduce diuretic-induced renal potassium loss. Potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride), potassium supplements and potassium-containing table salt substitutes can lead to a significant increase in serum potassium levels, including death. If simultaneous use of an ACE inhibitor and the above drugs is necessary (in case of confirmed hypokalemia), caution should be exercised and regular monitoring of potassium levels in the blood plasma and ECG parameters should be carried out.

Combination of drugs. requiring special attention

Oral hypoglycemic agents (sulfonylureas) and insulin: The following effects have been reported for captopril and enalapril. ACE inhibitors may enhance 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).

Combination of drugs. requiring attention

Allopurinol, cytostatic and immunosuppressive agents, corticosteroids (when used systemically) and procainamide: simultaneous use with ACE inhibitors may be accompanied by an increased risk of leukopenia.

Agents for general anesthesia: simultaneous use of ACE inhibitors and agents for general anesthesia may lead to an enhanced 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 flushing, nausea, vomiting, arterial hypotension.

Indapamide

Combination of drugs requiring special attention

Drugs that can cause torsades de pointes: due to the risk of hypokalemia, caution should be exercised when indapamide is used concomitantly with drugs that can cause torsades de pointes, such as antiarrhythmics (quinidine, hydroquinidine, disopyramide, amiodarone, dofetilide, ibutilide , bretylium tosylate, sotalol); some neuroleptics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine); benzamides (amisulpride, sulpiride, sultopride, tiapride); butyrophenones (droperidol, haloperidol); other antipsychotics (pimozide); other drugs such as bepridil, cisapride, difemanil methyl sulfate, erythromycin IV, halofantrine, mizolastine, moxifloxacin, pentamidine, sparfloxacin, vincamine IV, methadone, astemizole, terfenadine. Concomitant use with the above drugs should be avoided; the risk of developing hypokalemia, correct it if necessary; monitor the QT interval.

Drugs that can cause hypokalemia: amphotericin B (iv), gluco- and mineralocorticosteroids (when administered systemically), tetracosactide, laxatives that stimulate intestinal motility: increased risk of hypokalemia (additive effect). It is necessary to monitor the potassium content in the blood plasma and, if necessary, correct it. Particular attention should be paid to patients concomitantly receiving cardiac glycosides. Laxatives that do not stimulate intestinal motility should be used.

Cardiac glycosides: hypokalemia enhances the toxic effect of cardiac glycosides. With the simultaneous use of indapamide and cardiac glycosides, the content of potassium in the blood plasma and ECG readings should be monitored and, if necessary, therapy should be adjusted.

Combination of drugs. requiring attention

Metformin: functional renal failure, which can occur while taking diuretics, especially loop diuretics, with simultaneous administration of metformin increases the risk of developing lactic acidosis. Metformin should not be used if the plasma creatinine concentration exceeds 15 mg/l (135 µmol/l) in men and 12 mg/l (110 µmol/l) in women.

Calcium salts: with simultaneous administration, hypercalcemia may develop due to decreased excretion of calcium ions by the kidneys.

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

Dosage of Noliprel a forte

Orally, preferably in the morning, before meals.

Essential hypertension

1 tablet Noliprel® A forte 1 time per day.

If possible, taking the drug begins with selecting doses of single-component drugs. If clinically necessary, you can consider prescribing combination therapy with Noliprel® A forte immediately after monotherapy.

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

It is recommended to start therapy with a combination of perindopril/indapamide at a dose of 2.5 mg/0.625 mg (Noliprel® A) once a day. After 3 months of therapy, subject to good tolerance, it is possible to increase the dose - 1 tablet Noliprel® A forte 1 time per day.

Elderly patients

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

Kidney failure

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

For patients with moderately severe renal failure (creatinine clearance 30-60 ml/min), it is recommended to begin therapy with the required doses of drugs (in monotherapy) included in Noliprel® A forte.

Patients with CC equal to or exceeding 60 ml/min do not require dose adjustment. During therapy, regular monitoring of the concentration of creatinine and potassium in the blood plasma is necessary.

Liver failure

The drug is contraindicated in patients with severe liver failure. For moderately severe liver failure, no dose adjustment is required.

Children and teenagers

Noliprel® A 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 in this age group.

Overdose

Symptoms

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

Emergency measures are limited to removing the drug from the body: gastric lavage and/or administration of activated charcoal, followed by restoration of water and electrolyte balance.

If there is a significant decrease in blood pressure, the patient should be transferred to the “lying” position with his legs elevated. If necessary, correct hypovolemia (for example, intravenous infusion of 0.9% sodium chloride solution). Perindoprilat, the active metabolite of perindopril, can be removed from the body by dialysis.

Precautionary measures

Noliprel® A forte

The use of the drug Noliprel® A forte 5 mg + 1.25 mg is not accompanied by a significant reduction in the frequency of side effects, with the exception of hypokalemia, compared with perindopril and indapamide at the lowest approved doses. When initiating therapy with two antihypertensive drugs that the patient has not previously received, an increased risk of idiosyncrasy cannot be excluded. Careful monitoring of the patient can minimize this risk.

Renal dysfunction

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

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

Arterial hypotension and water-electrolyte imbalance

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

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

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

Potassium level

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

Excipients

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

Lithium preparations

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

Perindopril

Neutropenia/agranulocytosis

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

Angioedema (swelling

Bibliography:

1. Anatomical Therapeutic Chemical Classification (ATX);
2. Nosological classification (ICD-10);
3. Official instructions from the manufacturer.

Certificates Noliprel a forte

Prices for Noliprel a forte in Moscow pharmacies

Release form: Noliprel a forte 5 mg + 1.25 mg 30 pcs. film-coated tablets

List of pharmacies	Address	Opening hours	Price
Avicenna Pharma	Pervomayskaya Nizhny. st. 46	Around the clock	699.00 rub.
AVICENNA PHARMA No. 10	Vokzalnaya st., 27	Around the clock	699.00 rub.
ASNA	Kirovogradskaya st., 9, building 2	Mon-Fri: 08:00-22:00 Sat-Sun: 09:00-22:00	705.00 rub.
Avicenna Pharma	Sovkhoznaya st., 20	Around the clock	709.00 rub.
Harmony	Novotushinskaya st., 4	Mon-Sun: 09:00-22:00	673.00 rub.
Harmony	Leninsky Prospekt, 1, building 3	Mon-Sun: 08:00-22:00	712.00 rub.
Avicenna Pharma	Novoostapovskaya st., 4, building 1	Around the clock	717.00 rub.
PHARMACY MEDIAL SAVINGS	Yunosti pl., 2	Mon-Sun: 08:00-21:00	717.00 rub.
PHARMACY MEDIAL SAVINGS	Cor.612	Mon-Sun: 08:00-21:00	717.00 rub.
Avicenna Pharma	Vokzalnaya st., 21	Around the clock	719.00 rub.

Essential arterial hypertension. In patients with arterial hypertension and type 2 diabetes mellitus to reduce the risk of developing microvascular complications (from the kidneys) and macrovascular complications from cardiovascular diseases.

Contraindications Noliprel A forte tablets 1.25 mg + 5 mg

Hypersensitivity to perindopril and other ACE inhibitors, to indapamide and sulfonamides, as well as to other auxiliary components of the drug included in the drug; history of angioedema (including while taking other ACE inhibitors); hereditary/idiopathic angioedema; hypokalemia; severe renal failure (creatinine clearance less than 30 ml/min); stenosis of the artery of a single kidney; bilateral renal artery stenosis; severe liver failure (including with encephalopathy); simultaneous use of drugs that prolong the QT interval; simultaneous use of antiarrhythmic drugs that can cause ventricular arrhythmia of the “pirouette” type; pregnancy; lactation period (breastfeeding); Concomitant use of the drug with potassium-sparing diuretics, potassium and lithium preparations, and in case of hyperkalemia is not recommended. Due to the lack of sufficient clinical experience, the drug should not be used in patients with untreated decompensated heart failure and in patients on hemodialysis.

Directions for use and dosage Noliprel A forte tablets 1.25mg+5mg

Orally, preferably in the morning, before meals. Essential hypertension. Prescribe 1 tablet 1 time per day. If possible, taking the drug begins with selecting doses of single-component drugs. If clinically necessary, you can consider prescribing combination therapy with the drug immediately after monotherapy. In patients with arterial hypertension and type 2 diabetes mellitus to reduce the risk of developing microvascular complications from the kidneys and macrovascular complications from cardiovascular diseases. It is recommended to start therapy with a combination of perindopril/indapamide at a dose of 2.5 mg/0.625 mg once a day. After 3 months of therapy, subject to good tolerance, it is possible to increase the dose - 1 tablet 1 time per day. Elderly patients should be prescribed treatment with the drug after monitoring renal function and blood pressure. The drug is contraindicated in patients with severe renal failure (creatinine clearance 60 ml/min, no dose adjustment is required. During therapy, regular monitoring of the concentration of creatinine and potassium in the blood plasma is necessary. Liver failure. The drug is contraindicated in patients with severe liver failure. With moderate liver failure no dose adjustment is required.Children and adolescents.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 the drug in patients in this age group.

Servier Laboratories Servier Industry Laboratories Servier Industry Laboratories/ Serdix, LLC Serdix, LLC

Country of origin

Russia France France/Russia

Product group

Cardiovascular drugs

Antihypertensive combination drug. (angiotensin-converting enzyme inhibitor (ACE) + diuretic).

Release forms

• 14 - polypropylene bottles with dispenser (1) - cardboard packs with first opening control. 30 - polypropylene bottles with dispenser (1) - cardboard packs with first opening control. 30 - polypropylene bottles with dispenser (1) - cardboard packs with first opening control. Film-coated tablets 10 mg + 2.5 mg - 30 tablets per pack.

Description of the dosage form

• Round, biconvex, white, film-coated tablets. Film-coated tablets White film-coated tablets, oblong White film-coated tablets, oblong, scored on both sides. White, oblong, film-coated tablets.

pharmachologic effect

Noliprel® A Bi-forte is a combination drug containing perindopril arginine and indapamide. The pharmacological properties of the drug Noliprel® A Bi-forte combine the individual properties of each of the components. The combination of perindopril arginine and indapamide enhances the effect of each of them. Perindopril is an inhibitor of the enzyme that converts angiotensin I into angiotensin II (ACE inhibitor). ACE, or kininase II, is an exopeptidase that carries out both the conversion of angiotensin I into the vasoconstrictor substance angiotensin II, and the destruction of bradykinin, which has a vasodilatory effect, into an inactive heptapeptide. As a result, perindopril reduces the secretion of aldosterone, according to the principle of negative feedback, increases the activity of renin in the blood plasma, and with long-term use reduces the peripheral vascular resistance, which is mainly due to the effect on the vessels in the muscles and kidneys. These effects are not accompanied by salt and water retention or the development of reflex tachycardia. Perindopril normalizes myocardial function, reducing preload and afterload. When studying hemodynamic parameters in patients with chronic heart failure, the following was revealed: a decrease in filling pressure in the left and right ventricles of the heart; decrease in OPSS; increased cardiac output and increased cardiac index; increased muscle peripheral blood flow. Indapamide belongs to the group of sulfonamides; its pharmacological properties are similar to thiazide diuretics. Indapamide inhibits the reabsorption of sodium ions in the cortical segment of the loop of Henle, which leads to an increase in the excretion of sodium, chlorine and, to a lesser extent, potassium and magnesium ions by the kidneys, thereby increasing diuresis and reducing blood pressure. Antihypertensive effect of Noliprel®A Bi-forte Noliprel®A Bi-forte has a dose-dependent hypotensive effect on both diastolic and systolic blood pressure in the standing and lying position. The hypotensive effect of the drug persists for 24 hours. A stable therapeutic effect occurs less than 1 month from the start of therapy and is not accompanied by tachycardia. Stopping treatment does not cause withdrawal syndrome. Noliprel® A Bi-forte reduces the degree of left ventricular hypertrophy, improves arterial elasticity, reduces peripheral vascular resistance, and does not affect lipid metabolism (total cholesterol, HDL-cholesterol and LDL-cholesterol, triglycerides). The effect of the drug on cardiovascular morbidity and mortality has not been studied. The effect of the combination of perindopril and indapamide on left ventricular hypertrophy (LVH) compared with enalapril has been proven. In patients with arterial hypertension and LVH who received therapy with perindopril terbutylamine 2 mg (equivalent to 2.5 mg perindopril arginine)/indapamide 0.625 mg or enalapril at a dose of 10 mg 1 time/, and with an increase in the dose of perindopril to 8 mg (equivalent to 10 mg perindopril arginine) and indapamide up to 2.5 mg, or enalapril up to 40 mg 1 time/ a more significant decrease in left ventricular mass index (LVMI) was noted in the perindopril/indapamide group (-10.1 g/m2) compared to the indapamide group (-1.1 g/m2). The difference in the degree of reduction in this indicator between groups was -8.3 g/m2 (95% CI (-11.5, -5.0), p

Pharmacokinetics

The pharmacokinetic parameters of perindopril and indapamide when combined do not change compared to their separate use. Perindopril Absorption and metabolism After oral administration, perindopril is rapidly absorbed. Bioavailability is 65-70%. Cmax of perindoprilat in blood plasma is reached after 3-4 hours. Approximately 20% of the total amount of absorbed perindopril is converted into the active metabolite perindoprilat. When taking the drug with food, the conversion of perindopril to perindoprilat is reduced (this effect does not have significant clinical significance). Distribution and elimination Plasma protein binding is less than 30% and depends on the concentration of perindopril in the blood plasma. The dissociation of perindoprilate associated with ACE is slowed down. As a result, T1/2 is 25 hours. Repeated administration of perindopril does not lead to its accumulation, and T1/2 of perindoprilat upon repeated administration corresponds to the period of its activity, thus, an equilibrium state is achieved after 4. Perindopril penetrates the placental barrier. Perindoprilat is excreted from the body in the urine. T1/2 of perindoprilat is 3-5 hours. Pharmacokinetics in special clinical cases. The elimination of perindoprilat slows down in elderly patients, as well as in patients with renal failure and heart failure. The clearance of perindoprilate during dialysis is 70 ml/min. The pharmacokinetics of perindopril changes in patients with liver cirrhosis: the hepatic clearance of perindopril is reduced by 2 times. However, the concentration of the resulting perindoprilate does not change, so dose adjustment of the drug is not required. Indapamide Absorption Indapamide is quickly and completely absorbed from the gastrointestinal tract. Cmax in blood plasma is achieved 1 hour after oral administration. Distribution: Binding to plasma proteins - 79%. Repeated administration of the drug does not lead to its accumulation in the body. Elimination T1/2 is 14-24 hours (average 19 hours). It is excreted mainly in urine (70% of the administered dose) and in feces (22%) in the form of inactive metabolites. Pharmacokinetics in special clinical situations The pharmacokinetics of indapamide does not change in patients with renal failure.

Special conditions

Noliprel®A Bi-forte Impaired renal function Therapy with Noliprel®A Bi-forte is contraindicated in patients with moderate and severe renal failure (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 the drugs in monotherapy. Such patients require regular monitoring of the content of potassium ions and creatinine in the blood serum - 2 weeks after the start of therapy and then every 2 months. Renal failure occurs more often in patients with severe chronic heart failure or underlying renal impairment, 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 water-electrolyte imbalance 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, attention should be paid to possible symptoms of dehydration and decreased plasma electrolytes, for example, after diarrhea or vomiting. Such patients require regular monitoring of blood plasma electrolyte levels. In case of severe arterial hypotension, intravenous administration of 0.9% sodium chloride solution may be required. Transient arterial hypotension is not a contraindication for continued therapy. After restoration of blood volume and blood pressure, therapy can be resumed using low doses of a combination of perindopril and indapamide, or the drugs can be used as monotherapy. Potassium content The combined use of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal failure. As with the use of other antihypertensive drugs in combination with a diuretic, regular monitoring of the content of potassium ions in the blood plasma is necessary. Excipients It should be taken into account that the excipients of the drug include lactose monohydrate. The drug should not be prescribed to patients with hereditary galactose intolerance, lactase deficiency and glucose-galactose malabsorption. Perindopril Neutropenia/agranulocytosis The risk of developing neutropenia while taking ACE inhibitors is dose-dependent and depends on the drug taken and the presence of concomitant diseases. Neutropenia rarely occurs in patients without concomitant diseases, but the risk increases in patients with impaired renal function,

Compound

• perindopril arginine 10 mg, which corresponds to 6.79 mg perindopril and indapamide 2.5 mg. Excipients: lactose monohydrate 142.66 mg, magnesium stearate 0.90 mg, maltodextrin 18.00 mg, colloidal anhydrous silicon dioxide 0.54 mg, sodium carboxymethyl starch (type A) 5.40 mg. Film shell composition: macrogol 6000 0.27828 mg, magnesium stearate 0.26220 mg, titanium dioxide (E171) 0.83902 mg, glycerol 0.26220 mg, hypromellose 4.3583 mg. perindopril arginine 2.5 mg, which corresponds to the content of perindopril 1.6975 mg indapamide 625 mcg Excipients: sodium carboxymethyl starch (type A), colloidal anhydrous silicon dioxide, lactose monohydrate, magnesium stearate, maltodextrin. Film shell composition: macrogol 6000, SEPIFILM 37781 RBC (glycerol, hypromellose, macrogol-6000, magnesium stearate, titanium dioxide (E171)). perindopril arginine 5 mg, which corresponds to the content of perindopril 3.395 mg indapamide 1.25 mg Excipients: sodium carboxymethyl starch (type A), colloidal anhydrous silicon dioxide, lactose monohydrate, magnesium stearate, maltodextrin. Film shell composition: macrogol 6000, SEPIFILM 37781 RBC (glycerol, hypromellose, macrogol 6000, magnesium stearate, titanium dioxide (E171)). perindopril arginine 5 mg, which corresponds to the content of perindopril 3.395 mg indapamide 1.25 mg Excipients: sodium carboxymethyl starch (type A), colloidal anhydrous silicon dioxide, lactose monohydrate, magnesium stearate, maltodextrin. Film shell composition: macrogol 6000, SEPIFILM 37781 RBC (glycerol, hypromellose, macrogol 6000, magnesium stearate, titanium dioxide (E171)). perindopril arginine 10 mg, which corresponds to the content of perindopril 6.79 mg indapamide 2.5 mg Excipients: lactose monohydrate, magnesium stearate, maltodextrin, colloidal anhydrous silicon dioxide, sodium carboxymethyl starch (type A). Film shell composition: macrogol 6000, magnesium stearate, titanium dioxide (E171), glycerol, hypromellose.

Drug interactions

Noliprel® A Bi-forte Undesirable combination of drugs With the simultaneous use of lithium preparations and ACE inhibitors, a reversible increase in the content of lithium in the blood plasma and associated toxic effects may occur. Additional use of thiazide diuretics may further increase lithium levels and increase the risk of toxicity. The simultaneous use of a combination of perindopril and indapamide with lithium preparations is not recommended. In the case of such therapy, regular monitoring of the concentration of lithium in the blood plasma is necessary. Combination of drugs requiring special attention When used simultaneously with baclofen, the hypotensive effect may be enhanced. Blood pressure and renal function should be monitored and, if necessary, dose adjustment of antihypertensive drugs is required. When used simultaneously with NSAIDs, including high doses of acetylsalicylic acid (more than 3 g/day), a decrease in diuretic activity is possible.

Overdose

the most likely symptom of an overdose is a pronounced decrease in blood pressure, sometimes in combination with nausea, vomiting, convulsions, dizziness, drowsiness, confusion and oliguria, which can develop into anuria (as a result of hypovolemia)

Storage conditions

• keep away from children

Information provided Active substances: perindopril arginine 5 mg, which corresponds to 3.395 mg of perindopril and indapamide 1.25 mg.

pharmachologic effect

Noliprel A forte is a combination drug containing perindopril arginine and indalamide. The pharmacological properties of the drug combine the individual properties of each component. Mechanism of action. Noliprel A forte. The combination of perindopril and indapamide enhances the antihypertensive effect of each of them. Perindopril. Perindopril is an enzyme inhibitor, converting angiotensin I into angiotensin II (ACE inhibitor). ACE, or kininase II, is an exopeptidase that carries out both the conversion of angiotensin I into the vasoconstrictor substance angiotensin II, and the destruction of bradykinin, which has a vasodilatory effect, to an inactive heptapeptide. As a result, perindopril: reduces the secretion of aldosterone; according to the principle of negative feedback, it increases the activity of renin in blood plasma; with long-term use, it reduces the peripheral vascular resistance, which is mainly due to the effect on the vessels in the muscles and kidneys. These effects are not accompanied by sodium and fluid retention or the development of reflex tachycardia. Perindopril normalizes myocardial function, reducing preload and afterload. When studying hemodynamic parameters in patients with chronic heart failure, it was revealed: a decrease in filling pressure in the left and right ventricles of the heart; a decrease in peripheral resistance; an increase in cardiac output; an increase in muscle peripheral blood flow. Indapamide. Indapamide refers to to the group of sulfonamides, its pharmacological properties are similar to thiazide diuretics. Indapamide inhibits the reabsorption of sodium ions in the cortical segment of the loop of Henle, which leads to an increase in the excretion of sodium, chlorine and, to a lesser extent, potassium and magnesium ions by the kidneys, thereby increasing diuresis and reducing blood pressure. Antihypertensive effect. Noliprel A forte. Noliprel A forte has a dose-dependent effect antihypertensive effect on both diastolic and systolic blood pressure in a standing and lying position. The antihypertensive effect lasts for 24 hours. A stable therapeutic effect develops in less than 1 month from the start of therapy and is not accompanied by tachycardia. Discontinuation of treatment does not cause withdrawal syndrome. Noliprel A forte reduces the degree of left ventricular hypertrophy (LVH), improves arterial elasticity, reduces peripheral vascular resistance, and does not affect lipid metabolism (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides). The effect of using a combination of perindopril and indapamide has been proven. on LVT compared with enalapril. In patients with arterial hypertension and LVH who received therapy with perindopril erbumine 2 mg (equivalent to 2.5 mg perindopril arginine)/indapamide 0.625 mg or enalapril at a dose of 10 mg 1 time per day, and with an increase in the dose of perindopril erbumine to 8 mg (equivalent to 10 mg perindopril arginine) and indapamide up to 2.5 mg, or enalapril up to 40 mg 1 time per day, a more significant decrease in left ventricular mass index (LVMI) was noted in the perindopril/indapamide group compared with the enalapril group. At the same time, the most significant effect on LVMI was observed with the use of perindopril erbumine 8 mg/indapamide 2.5 mg. A more pronounced antihypertensive effect was also noted during combination therapy with perindopril and indapamide compared with enalapril. In patients with type 2 diabetes mellitus (average values ​​- age 66 years, body mass index 28 kg/m2, glycosylated hemoglobin (HbA1c) 7.5%, blood pressure 145/81 mm Hg) studied the effect of a fixed combination of perindopril/indapamide on the main micro- and macrovascular complications in addition to both standard glycemic control therapy and intensive glycemic control (IGC) strategy (target HbA1c Indications for use Essential arterial hypertension. In patients with arterial hypertension and type 2 diabetes mellitus to reduce the risk of developing microvascular complications (from the kidneys) and macrovascular complications from cardiovascular diseases.

Mode of application

Orally, preferably in the morning, before meals. Essential hypertension. Prescribe 1 tablet once a day. If possible, start taking the drug by selecting doses of single-component drugs. If clinically necessary, you can consider prescribing combination therapy with the drug immediately after monotherapy. In patients with arterial hypertension and type 2 diabetes mellitus, to reduce the risk of developing microvascular complications from the kidneys and macrovascular complications from cardiovascular diseases. It is recommended to start therapy with a combination of perindopril/indapamide at a dose of 2.5 mg/0.625 mg 1 time per day. After 3 months of therapy, subject to good tolerability, it is possible to increase the dose - 1 tablet 1 time per day. Elderly patients should be prescribed treatment with the drug after monitoring renal function and blood pressure. The drug is contraindicated in patients with severe renal failure (QC Interaction Combinations, not recommended for use. Lithium preparations: with simultaneous use of lithium preparations and ACE inhibitors, a reversible increase in the concentration of lithium in the blood plasma and associated toxic effects may occur. Additional administration of thiazide diuretics may further increase the concentration of lithium and increase the risk of toxicity. Simultaneous 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. Drugs, the combination with which requires special attention and caution. Baclofen: the hypotensive effect may be enhanced. Blood pressure and renal function should be monitored, and if necessary, dose adjustment of antihypertensive drugs is required. NSAIDs, including high doses of acetylsalicylic acid (more than 3 g/day): the administration of NSAIDs may lead to a decrease in diuretic, natriuretic and antihypertensive effects. With significant fluid loss, acute renal failure may develop (due to a decrease in glomerular filtration rate). Before starting treatment with the drug, it is necessary to replace fluid loss and regularly monitor renal function at the beginning of treatment. Combination of drugs that require attention. Tricyclic antidepressants, antipsychotics (neuroleptics): drugs of these classes enhance the antihypertensive effect and increase the risk of orthostatic hypotension (additive effect). Corticosteroids, tetracosactide: decreased antihypertensive effect (retention of fluid and sodium ions as a result of the action of corticosteroids). Other antihypertensive drugs: the antihypertensive effect may be enhanced. Perindopril. Combinations not recommended for use Potassium-sparing diuretics (amiloride, spironolactone, triamterene) and potassium preparations: ACE inhibitors reduce the loss of potassium by the kidneys caused by the diuretic. Potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride), potassium supplements and potassium-containing table salt substitutes can lead to a significant increase in serum potassium levels, including death. If simultaneous use of an ACE inhibitor and the above drugs is necessary (in 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. A combination of drugs that requires special attention. Hypoglycemic agents for oral administration (sulfonylurea derivatives) and Insulin: The following effects have been reported for captopril and enalapril. ACE inhibitors may enhance 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). Combination of drugs that require attention. Allopurinol, cytotoxic and immunosuppressive agents, corticosteroids (when used systemically) and procainamide: simultaneous use with ACE inhibitors may be accompanied by an increased risk leukopenia. Drugs for general anesthesia: simultaneous use of ACE inhibitors and drugs for general anesthesia can lead to increased antihypertensive effect. Diuretics (thiazide and loop): the use of diuretics in high doses can lead to hypovolemia, and the addition of perindopril to arterial hypertension hypotension. Gold preparations: when using ACE inhibitors, incl. perindopril in patients receiving intravenous gold (sodium aurothiomalate), a symptom complex was described, including: facial skin flushing, nausea, vomiting, arterial hypotension. Indapamide. A combination of drugs that requires special attention. Drugs that can cause pirouette-type arrhythmia ": due to the risk of developing hypokalemia, caution should be exercised when using indapamide simultaneously with drugs that can cause torsades de pointes, for example, antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide, amiodarone, dofetilide, ibutilide, bretylium tosylate, sotalol); some neuroleptics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine); benzamides (amisulpride, sulpiride, sultopride, tiapride); butyrophenones (droperidol, haloperidol); other antipsychotics (pimozide); other drugs such as bepridil, cisapride, difemanil methyl sulfate, erythromycin IV, halofantrine, mizolastine, moxifloxacin, pentamidine, sparfloxacin, vincamine IV, methadone, astemizole, terfenadine. Concomitant use with the above drugs should be avoided; the risk of developing hypokalemia, correct it if necessary; control the QT interval. Drugs that can cause hypokalemia: amphotericin B (iv), gluco- and mineralocorticosteroids (when administered systemically), tetracosactide, laxatives that stimulate intestinal motility: increased risk of hypokalemia (additive effect). It is necessary to monitor the potassium content in the blood plasma and, if necessary, correct it. Particular attention should be paid to patients concomitantly receiving cardiac glycosides. Laxatives that do not stimulate intestinal motility should be used. Cardiac glycosides: hypokalemia enhances the toxic effect of cardiac glycosides. With the simultaneous use of indapamide and cardiac glycosides, the potassium content in the blood plasma and ECG readings should be monitored and, if necessary, therapy should be adjusted. A combination of drugs that requires attention. Metformin: functional renal failure, which can occur while taking diuretics, especially loop ones, with simultaneous administration of metformin increases the risk of developing lactic acidosis. Metformin should not be used if the plasma creatinine concentration exceeds 15 mg/l (135 µmol/l) in men and 12 mg/l (110 µmol/l) in women. Iodine-containing contrast agents: dehydration of the body while taking diuretics increases the risk of developing acute renal failure, especially when using high doses of iodine-containing contrast agents. Before using iodinated contrast agents, patients need to compensate for fluid loss. Calcium salts: with simultaneous administration, hypercalcemia may develop due to decreased excretion of calcium ions by the kidneys. Cyclosporine: it is possible to increase the concentration of creatinine in the blood plasma without changing the concentration of cyclosporine in the blood plasma, even with normal water content and sodium ions.

Side effect

Perindopril has an inhibitory effect on the renin-angiotensin-aldosterone system (RAAS) and reduces the excretion of potassium ions by the kidneys while taking indapamide. In 4% of patients, while using the drug, hypokalemia develops (potassium level less than 3.4 mmol/l). From the circulatory and lymphatic systems: 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. From the central nervous system: often - paresthesia, headache, dizziness, asthenia, vertigo; infrequently - sleep disturbance, mood lability; very rarely - confusion; unspecified frequency - fainting. From the organ of vision: often - blurred vision. From the organ of hearing: often - tinnitus. From the cardiovascular system: often - a pronounced decrease in blood pressure, incl. orthostatic hypotension; very rarely - heart rhythm disturbances, incl. bradycardia, ventricular tachycardia, atrial fibrillation, as well as angina pectoris and myocardial infarction, possibly due to an excessive decrease in blood pressure in high-risk patients; unspecified frequency - pirouette-type arrhythmias (possibly fatal). From the respiratory system: often - during the use of ACE inhibitors, a dry cough may occur, which persists for a long time while taking drugs of this group and disappears after their withdrawal; dyspnea; infrequently - bronchospasm; very rarely - eosinophilic pneumonia, rhinitis. From the digestive system: often - dry oral mucosa, nausea, vomiting, abdominal pain, epigastric pain, impaired taste perception, decreased appetite, dyspepsia, constipation, diarrhea; very rarely - angioedema of the intestine, cholestatic jaundice, pancreatitis; unspecified frequency - hepatic encephalopathy in patients with liver failure, hepatitis. From the skin and subcutaneous fat: often - skin rash, itching, maculopapular rash; uncommon - angioedema of the face, lips, extremities, mucous membrane of the tongue, vocal folds and/or larynx, urticaria, hypersensitivity reactions in patients predisposed to broncho-obstructive and allergic reactions, purpura. In patients with acute form of systemic lupus erythematosus, the course of the disease may worsen. Very rarely - erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome. There have been cases of photosensitivity reactions. From the musculoskeletal system: often - muscle spasms. From the urinary system: infrequently - renal failure; very rarely - acute renal failure. From the reproductive system: infrequently - impotence. General disorders and symptoms: often - asthenia; infrequently - increased sweating. Laboratory indicators: hyperkalemia (usually transient), a slight increase in the concentration of creatinine in the urine and in the blood plasma, which occurs after discontinuation of therapy, more often in patients with renal artery stenosis, when treating hypertension with diuretics and in the case of renal failure; rarely - hypercalcemia; unspecified frequency - an increase in the QT interval on the ECG, an increase in the concentration of uric acid and glucose in the blood, an increase in the activity of liver enzymes, hypokalemia, especially significant for patients at risk, hyponatremia and hypovolemia, leading to dehydration and orthostatic hypotension. Concomitant hypochloremia may lead to compensatory metabolic alkalosis (the likelihood and severity of this effect is low). Adverse effects noted during clinical trials. Adverse effects noted during the ADVANCE study are consistent with the previously established safety profile of the combination of perindopril and indapamide. Serious adverse events were noted in some patients in the study groups: hyperkalemia (0.1%), acute renal failure (0.1%), hypotension (0.1%) and cough (0.1%). Three patients in the perindopril/indapamide group experienced angioedema (versus 2 in the placebo group).

Contraindications

Hypersensitivity to perindopril and other ACE inhibitors, to indapamide and sulfonamides, as well as to other auxiliary components of the drug included in the drug; history of angioedema (including while taking other ACE inhibitors); hereditary/idiopathic angioedema ;hypokalemia; severe renal failure (creatinine clearance less than 30 ml/min); stenosis of the artery of a single kidney; bilateral stenosis of the renal arteries; severe liver failure (including encephalopathy); simultaneous use of drugs that prolong the QT interval; simultaneous use of antiarrhythmic drugs drugs that can cause ventricular arrhythmia of the "pirouette" type; pregnancy; lactation period (breastfeeding); simultaneous use of the drug with potassium-sparing diuretics, potassium and lithium drugs and hyperkalemia is not recommended. Due to the lack of sufficient clinical experience, the drug should not be used in patients with untreated decompensated heart failure and in patients on hemodialysis.

Overdose

Symptoms. The most likely symptom of an overdose is a pronounced decrease in blood pressure, sometimes in combination with nausea, vomiting, convulsions, dizziness, drowsiness, confusion, oliguria, which can turn into anuria (as a result of hypovolemia), water-electrolyte imbalance (hyponatremia, hypokalemia ). Treatment. Emergency measures are limited to removing the drug from the body: gastric lavage and/or administration of activated carbon, correction of water and electrolyte balance. If blood pressure decreases significantly, the patient should be transferred to the “lying” position with legs elevated. If necessary, correct hypovolemia (for example, intravenous infusion of 0.9% sodium chloride solution). Perindoprilat, the active metabolite of perindopril, can be removed from the body by dialysis.

special instructions

Pregnancy and lactation. The drug is contraindicated during pregnancy. If you are planning pregnancy or if it occurs while taking the drug, you should immediately stop taking the drug and prescribe other antihypertensive therapy. The drug should not be used in the first trimester of pregnancy. There are no appropriate controlled studies on the use of ACE inhibitors in No pregnant women were tested. The limited available data 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. The drug is contraindicated in the second and third trimesters of pregnancy. It is known that long-term exposure of the fetus to ACE inhibitors in the second and third trimesters of pregnancy can lead to disruption of its development (decreased renal function, oligohydramnios, delayed ossification of the skull bones) and the development of complications in the newborn (renal failure, arterial 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 growth retardation. In rare cases, while taking diuretics shortly before birth, newborns develop hypoglycemia and thrombocytopenia. If the patient received the drug during the second or third trimester of pregnancy, it is recommended to conduct an ultrasound examination of the newborn to assess the condition of the skull and renal function. In newborns whose mothers received therapy with ACE inhibitors, arterial hypotension may occur, and therefore newborns should be under careful medical care observation. The drug 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. In this case, the newborn may develop increased sensitivity to sulfonamide derivatives, hypokalemia and kernicterus. 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 stop taking drug. The use of the drug 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 doses approved for use. When initiating therapy with two antihypertensive drugs that the patient has not previously received, an increased risk of idiosyncrasy cannot be excluded. To minimize this risk, careful monitoring of the patient's condition should be carried out. Renal failure. In patients with severe renal failure (SC

A drug Noliprel Available in several different types. All variations of the drug include: indapamide . Combination tablets Noliprel contain 2 mg of perindopril and 0.625 mg of indapamide. Ingredients: Noliprel Forte includes 4 mg of perindopril and 1.25 mg of indapamide. Noliprel A contains 2.5 mg of perindopril and 0.625 mg of indapamide. In this drug, perindopril is associated with the amino acid arginine, which has a beneficial effect on the condition of the cardiovascular system.

In tablets Noliprel A Forte - 5 mg perindopril and 1.25 mg indapamide. In the facility Noliprel A Bi-forte - 10 mg perindopril and 2.5 mg indapamide.

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

Release form

The drugs are available in the form of white oblong tablets, with a score on both sides of the tablet. Fits in cardboard packaging of 14 and 30 pcs. in blisters.

pharmachologic effect

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

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

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

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

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

Pharmacokinetics and pharmacodynamics

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

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

The simultaneous use of calcium salts can provoke hypercalcemia.

Noliprel's analogs

Level 4 ATX code matches:

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

For children

The drug is not prescribed for the treatment of children under 18 years of age, since there is no accurate data on the effectiveness and safety of such treatment.

With alcohol

You should not drink alcohol during Noliprel therapy.

During pregnancy and lactation

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

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

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