Noliprel - instructions for use, analogs, reviews and release forms (tablets - A, Forte, Bi-Forte 2.5 mg, 5 mg and 10 mg) of the drug for the treatment of arterial hypertension in adults, children and in pregnancy

In this article, you can read the instructions for using the drug Noliprel. There are reviews of visitors to the site - consumers of this medication, as well as opinions of doctors of specialists on the use of Noliprel in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of Noliprel with available structural analogs. Use to treat hypertension and reduce blood pressure in adults, children, as well as during pregnancy and lactation.

Noliprel - combined preparation containing Perindopril (ACE inhibitor) and Indapamide (thiazide-like diuretic). Pharmacological action of the drug is due to a combination of individual properties of each of the components. The combined use of perindopril and indapamide provides synergism of the antihypertensive effect compared to each of the components alone.

The drug has a pronounced dose-dependent antihypertensive effect on both systolic and diastolic blood pressure in a supine and standing position. The drug lasts 24 hours. A persistent clinical effect occurs less than 1 month after the start of therapy and is not accompanied by tachycardia. Termination of treatment is not accompanied by the development of withdrawal syndrome.

Noliprel reduces the degree of left ventricular hypertrophy, improves the elasticity of the arteries, reduces round, it does not affect lipid metabolism (total cholesterol, LDL-HDL, LDL-C, triglycerides).

Perindopril - an inhibitor of angiotensin converting enzyme to angiotensin 2. 1 angiotensin converting enzyme (ACE), or kinase, is an exopeptidase, which carries out both the conversion of angiotensin 1 to angiotensin 2, which has vasoconstrictor action, and the destruction of bradykinin,having a vasodilating action, to an inactive heptapeptide. As a result, perindopril reduces the secretion of aldosterone, 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 the vessels in the muscles and kidneys. These effects are not accompanied by a delay in salts and water or the development of reflex tachycardia with prolonged use.

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

Against the background of the use of perindopril there is a decrease in both systolic and diastolic blood pressure in the supine and standing position. The withdrawal of the drug does not lead to an increase in blood pressure.

Perindopril has vasodilating effect, contributes to the restoration of elasticity and large arteries of the vascular wall structure of small arteries and reduces left ventricular hypertrophy.

Perindopril normalizes the heart, reducing preload and postnagruzku.

The combined use of thiazide diuretics increases the antihypertensive effect.In addition, the combination of an ACE inhibitor and a thiazide diuretic also leads to a reduction in the risk of hypokalemia with diuretics.

In patients with heart failure, perindopril causes a decrease in filling pressure in the right and left ventricles, a decrease in OPSS, an increase in cardiac output and an improvement in the cardiac index, and an increase in regional blood flow in the muscles.

Indapamide - a derivative of sulfonamide, by pharmacological properties is close to thiazide diuretics. Inhibits the reabsorption of sodium ions in the cortical segment of the Henle loop, which leads to an increase in urinary excretion of sodium, chlorine and, to a lesser extent, potassium and magnesium ions, thereby increasing diuresis. The hypotensive effect is manifested in doses that do not cause a diuretic effect.

Indapamide reduces hyperreactivity of blood vessels in relation to adrenaline.

Indapamide does not affect the lipid levels in the blood plasma (triglycerides, cholesterol, LDL and HDL), carbohydrate metabolism (including in patients with concomitant diabetes mellitus).

Indapamide reduces the hypertrophy of the left ventricle.

Composition

Perindopril arginine + Indapamide + auxiliary substances.

Pharmacokinetics

The pharmacokinetic parameters of perindopril and indapamide in combination do not change as compared to their separate use.

Perindopril

After ingestion perindopril quickly absorbed. Approximately 20% of the total amount of absorbed perindopril is converted to the active metabolite perindoprilat. When taking the drug during meals, the perindopril is converted into perindoprilat (this effect has no significant clinical significance). Perindoprilat is excreted from the body with urine. T1 / 2 perindoprilata is 3-5 hours. The excretion of perindoprilat is slowed down in elderly patients, as well as in patients with renal insufficiency and heart failure.

Indapamide

Indapamide is rapidly and completely absorbed from the digestive tract. The repeated use of the drug does not lead to its cumulation in the body. It is excreted mostly with urine (70% of the administered dose) and with feces (22%) in the form of inactive metabolites.

Indications

• essential arterial hypertension.

Forms of release

Tablets 2.5 mg (Nolipret A).

Tablets 5 mg (Nolipret A Forte).

Tablets 10 mg (Noliprel A B-Forte).

Instructions for use and dosage

Assign inside, preferably in the morning, before eating, 1 tablet 1 time per day. If, after 1 month after initiation of therapy, the desired antihypertensive effect has not been achieved, the dose of the drug can be increased to a dose of 5 mg (available under the trade name Noliprel A forte).

For elderly patients, therapy should be started with 1 tablet 1 time per day.

Noliprel should not be given to children and adolescents because of the lack of data on efficacy and safety in patients of this age group.

Side effect

• dry mouth;
• nausea;
• decreased appetite;
• abdominal pain;
• violation of taste;
• constipation;
• a dry cough that persists for a long time during the intake of drugs of this group and disappears after their withdrawal;
• orthostatic hypotension;
• hemorrhagic rash;
• rashes on the skin;
• exacerbation of systemic lupus erythematosus;
• angioedema (edema of Quincke);
• photosensitivity reaction;
• paresthesia;
• headache;
• asthenia;
• sleep disturbance;
• mood lability;
• dizziness;
• muscle spasms;
• Thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia;
• hypokalemia (especially significant for patients at risk), hyponatremia, hypovolemia, leading to dehydration and orthostatic hypotension, hypercalcemia.

Contraindications

• angioedema in the anamnesis (including against the background of taking other ACE inhibitors);
• hereditary / idiopathic angioedema;
• renal failure of severe degree (CK <30 ml / min);
• hypokalemia;
• bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney;
• severe hepatic insufficiency (including with encephalopathy);
• simultaneous reception of drugs that extend the QT interval;
• simultaneous administration of antiarrhythmic agents that can cause ventricular arrhythmia of the "pirouette" type;
• pregnancy;
• lactation period (breastfeeding);
• hypersensitivity to perindopril and other ACE inhibitors, to indapamide and sulfonamides, as well as to other auxiliary components of the drug.

Application in pregnancy and lactation

The drug should not be used in the first trimester of pregnancy.

When planning a pregnancy or when it comesAgainst the background of the drug Noliprel should immediately stop taking the drug and prescribe another antihypertensive therapy.

Appropriate controlled trials of ACE inhibitors in pregnant women have not been conducted. The available limited data on the effect of the drug in the first trimester of pregnancy indicate that the administration of the drug did not lead to malformations associated with fetotoxicity.

Noliprel is contraindicated in the 2nd and 3rd trimesters of pregnancy.

It is known that prolonged exposure to ACE inhibitors on the fetus in the 2nd and 3rd trimester of pregnancy can lead to disruption of its development (decreased kidney function, oligohydramnion, delayed skull formation) and complications in the newborn (kidney 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 delayed fetal development. In rare cases, against the background of diuretics shortly before delivery, neonates develop hypoglycemia and thrombocytopenia.

If the patient received Noliprel in 2 or 3 trimesters of pregnancy, it is recommended to perform an ultrasound examination of the fetus to assess the condition of the skull and kidney function.

Noliprel is contraindicated during lactation.

special instructions

The use of Noliprel is not accompanied by a significant reduction in the incidence of side effects, with the exception of hypokalemia, compared with perindopril and indapamide at the lowest dose permitted for use. At the beginning of therapy with two antihypertensive drugs, which the patient did not receive earlier, one can not exclude the increased risk of idiosyncrasy. To minimize this risk, careful monitoring of the patient's condition should be carried out.

Renal insufficiency

In patients with severe renal insufficiency (CC <30 mL / min), this combination is contraindicated.

In some patients with hypertension without a previous impairment of renal function against the background of Noliprel therapy, laboratory signs of functional renal failure may appear. In this case, treatment should be discontinued. In the future, you can resume combination therapy, using low doses of drugs, or use drugs in monotherapy.Such patients need regular monitoring of the level of potassium and creatinine in the blood serum - 2 weeks after the start of therapy and then every 2 months. Renal failure often occurs in patients with severe chronic heart failure or an initial impairment of kidney function, incl. with stenosis of the renal artery.

Arterial hypotension and disturbance of water-electrolyte balance

Hyponatremia is associated with a risk of sudden development of arterial hypotension (especially in patients with artery stenosis of a single kidney and bilateral stenosis of the renal arteries). Therefore, when observing patients dynamically, 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 the level of plasma electrolytes. With severe arterial hypotension, a 0.9% solution of sodium chloride may be required.

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

The content of potassium

The combination of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or with renal insufficiency. As with any antihypertensive drug in combination with a diuretic, the treatment with this combination should regularly monitor the potassium content in the blood plasma.

Excipients

It should be borne in mind that the composition of excipients of the drug includes lactose monohydrate. Do not administer Noliprel to patients with hereditary intolerance to galactose, lactase deficiency, and glucose-galactose malabsorption.

Neutropenia / agranulocytosis

The risk of developing neutropenia against the background of the administration of 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 the withdrawal of ACE inhibitors, neutropenia signs pass independently. To avoid the development of such reactions it is recommended to strictly follow the recommended dose.In the appointment of ACE inhibitors, this group of patients should carefully balance the benefit / risk factor.

Angioedema (edema of Quincke)

In rare cases, angiotoneurotic edema of the face, extremities, mouth, tongue, pharynx and / or larynx develops against ACE inhibitor therapy. In such a situation, you should immediately stop taking perindopril and ensure that the patient's condition is monitored until the edema disappears completely. If swelling only affects the face and mouth, the manifestations usually go away without special treatment, but for faster relief of symptoms, you can use antihistamines.

Angioedema, accompanied by swelling of the larynx, can lead to death. Swelling of the tongue, throat or larynx can lead to airway obstruction. In this case, epinephrine (epinephrine) must be injected immediately at a dose of 1: 1000 (0.3 to 0.5 ml) and take other emergency measures. Patients with a history of Quincke edema not associated with the administration of ACE inhibitors have an increased risk of developing Quincke's edema when taking these drugs.

In rare cases, against the background of therapy with ACE inhibitors, angioedema develops in the intestine.

Anaphylactic reactions during desensitization

There are separate reports on the development of life-threatening anaphylactic reactions in patients receiving ACE inhibitors during desensitizing therapy with venom of Hymenoptera insects (including bee, aspen). ACE inhibitors should be given with caution to patients prone to allergic reactions and undergoing desensitization procedures. It should avoid the appointment of the drug to patients receiving immunotherapy with venom of Hymenoptera insects. However, anaphylactic reactions can be avoided by temporarily discontinuing the drug at least 24 hours before the start of the course of desensitizing therapy.

Cough

Against the background of therapy with an ACE inhibitor, dry cough may occur. Cough persists for a long time against the background of taking this group's drugs and disappears after their withdrawal. When a patient has a dry cough, remember 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.

The risk of arterial hypotension and / or renal failure (including in the case of heart failure, water deficiency and electrolytes)

In some pathological states, a significant activation of the renin-angiotensin-aldosterone system can occur, especially with pronounced hypovolemia and a decrease in the level of plasma electrolytes (against a background of a salt-free diet or long-term diuretics), in patients with initially low blood pressure, bilateral stenosis of the renal arteries or 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 can be accompanied by a sharp decrease in blood pressure and / or an increase in the level of creatinine in the blood plasma, indicating the development of functional renal failure. These phenomena are more often observed with the first dose of the drug or during the first two weeks of therapy. Sometimes these conditions develop rapidly in other periods of therapy. In such cases, when the therapy is resumed, it is recommended to use the drug in a lower dose and then gradually increase the dose.

Elderly patients

Before you start taking the drug, you need to assess the functional activity of the kidneys and the concentration of potassium in the blood plasma.At the beginning of therapy, the dose of the drug is selected, given the degree of BP reduction, especially in the case of dehydration and loss of electrolytes. Such measures allow to avoid a sharp decrease in blood pressure.

Patients with established atherosclerosis

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

Renovascular hypertension

The method of treating reninvascular hypertension is revascularization. Nevertheless, the use of ACE inhibitors has a beneficial effect in this category of patients, both anticipating surgical intervention, and in the case when surgical intervention can not be carried out. Treatment with Noliprelol for patients with diagnosed or suspected bilateral stenosis of the renal arteries or stenosis of the single kidney artery should begin with a low dose of the drug in a hospital setting, monitoring the kidney function and the concentration of potassium in the blood plasma. In some patients, functional renal failure may develop, which disappears when the drug is withdrawn.

Other risk groups

In patients with severe heart failure (stage IV) and patients with insulin-dependent diabetes mellitus (the risk of spontaneous increase in the level of potassium), the drug should be started with low doses and monitored by a doctor.

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

Anemia

Anemia can develop in patients who have undergone kidney transplantation, or in patients on hemodialysis. The higher the initial level of hemoglobin, the more pronounced its decrease. This effect, apparently, is not dose-dependent, but may be related to the mechanism of action of ACE inhibitors. Reduction of hemoglobin is insignificant, it occurs within the first 1-6 months of treatment, and then stabilizes. If treatment is canceled, the hemoglobin level is completely restored. The treatment can be continued under the control of the picture of peripheral blood.

Surgery / General Anesthesia

The use of ACE inhibitors in patients,subject to surgery with general anesthesia, can lead to a marked decrease in blood pressure, especially when using funds for general anesthesia that have antihypertensive effects. It is recommended to stop taking long-acting ACE inhibitors, incl. perindopril, the day before the surgery. It is necessary to warn the anesthesia doctor that the patient is taking ACE inhibitors.

Aortic stenosis / Hypertrophic cardiomyopathy

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

Liver failure

In rare cases, when taking ACE inhibitors, cholestatic jaundice occurs. With the progression of this syndrome, rapid development of liver necrosis, sometimes fatal, is possible. The mechanism of development of this syndrome is unclear. If jaundice or a significant increase in hepatic enzyme activity when taking ACE inhibitors, the patient should stop taking the drug and consult a doctor.

Indapamide

In the presence of violations of the liver, the use of thiazide and thiazide-like diuretics can lead to the development of hepatic encephalopathy. In this case, stop taking the medication immediately.

Violations of the water-electrolyte balance

Before the start of treatment it is necessary to determine the content of sodium ions in the blood plasma. Against the background of taking the drug should regularly monitor this figure. All diuretic drugs 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 elderly people

Therapy with thiazide and thiazide-like diuretics is associated with a risk of hypokalemia. It is necessary to avoid hypokalemia (less than 3.4 mmol / l) in the following categories of patients at high risk: elderly, depleted patients or receiving concomitant medication, patients with cirrhosis, peripheral edema or ascites, coronary artery disease, heart failure. Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of arrhythmias. Patients with an increased QT interval also belong to the high-risk group, it does not matter,this increase is caused by innate causes or effects of drugs.

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

If hypokalemia is detected, appropriate treatment should be prescribed.

Thiazide and thiazide-like diuretics reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in the concentration of calcium in the blood plasma. Expressed hypercalcemia may be a consequence of previously not diagnosed hyperparathyroidism. Before the study of the function of the parathyroid gland, diuretic drugs should be withdrawn.

The content of glucose in the blood

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

Uric acid

In patients with high levels of uric acid in the blood, the risk of developing gout increases with Noliprel therapy.

Kidney function and diuretics

Thiazide and thiazide diuretics fully effective only in patients with normal or mildly impaired renal function (creatinine in blood plasma of adult individuals below 2.5 mg / dL or 220 pmol / l). At the beginning of treatment with diuretics in patients due to hypovolemia and hyponatremia may be a temporary reduction in glomerular filtration rate and an increase in the concentration of urea and creatinine in the blood plasma. This transient functional renal failure is not dangerous for patients with unchanged renal function, however, in patients with renal insufficiency, its severity may increase.

Photosensitivity

Against the background of taking thiazide and thiazide-like diuretics, cases of development of photosensitivity reactions were reported. In the case of developing photosensitivity reactions against the background of taking the drug should stop treatment. If it is necessary to continue therapy with diuretics, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays.

Athletes

Indapamide can give a positive reaction during doping control.

Impact on the ability to drive vehicles and manage mechanisms

The action of substances that make up the drug Noliprel does not lead to a disturbance of psychomotor reactions. However, in some people in response to a decrease in blood pressure, various individual reactions may develop, especially at the beginning of therapy or when adding other antihypertensive drugs to the therapy. In this case, the ability to drive a car or other mechanisms can be reduced.

Drug Interactions

Noliprel

Combinations that are not recommended for use

With simultaneous use of lithium drugs and ACE inhibitors, a reversible increase in the concentration of lithium in the blood plasma and associated toxic effects may occur. The additional administration of thiazide diuretics may further increase the concentration of lithium and increase the risk of toxicity. The simultaneous use of a combination of perindopril and indapamide with lithium preparations is not recommended. If this therapy is necessary, the lithium content in the blood plasma should be constantly monitored.

Combinations where special care is required

Baclofen increases the hypotensive effect of Noliprel. With simultaneous use, you should carefully monitor blood pressure and kidney function and the need to adjust the dose of Noliprel.

When used simultaneously with non-steroidal anti-inflammatory drugs (NSAIDs), including Acetylsalicylic acid in high doses (more than 3 g per day), a decrease in diuretic, natriuretic and hypotensive effect is possible. With a significant loss of fluid, acute renal failure may develop (due to a decrease in glomerular filtration). Before starting treatment, the drug should be filled with fluid loss and at the beginning of treatment carefully monitor kidney function.

Combinations where caution is required

With the simultaneous use of Noliprel and tricyclic antidepressants, neuroleptics may increase the hypotensive effect and increase the risk of developing orthostatic hypotension (additive effect).

Glucocorticosteroids (GCS), tetracosactide reduce the hypotensive effect of Noliprel (water and electrolyte retention due to GCS).

Other antihypertensives enhance Noliprel's action.

Perindopril

Combinations that are not recommended for use

ACE inhibitors reduce the excretion of potassium by the kidney caused by a diuretic. Potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride), potassium preparations and potassium-containing substitutes for edible salt can lead to a significant increase in serum potassium concentration up to a lethal outcome. If the combined use of an ACE inhibitor and the above preparations is necessary (in the case of confirmed hypokalemia), caution should be exercised and regular monitoring of potassium concentration in the blood plasma and ECG parameters should be performed.

Combinations where special care is required

With the use of ACE inhibitors (captopril, enalapril) in patients with diabetes mellitus, hypoglycemic action of insulin and sulfonylurea derivatives may be increased. The states of hypoglycemia are extremely rare (due to increased tolerance to glucose and a decrease in the need for insulin).

Combinations where caution is required

With the use of ACE inhibitors, allopurinol, cytostatic or immunosuppressive agents, systemic SCS or procainamide increase the risk of developing leukopenia.

ACE inhibitors can enhance the antihypertensive effect of agents for general anesthesia.

Prior treatment with diuretics (thiazide and "loop") in high doses can cause a decrease in bcc and arterial hypotension in the appointment of perindopril.

Indapamide

Combinations where special care is required

Because of the risk of developing hypokalemia, caution should be exercised when using indapamide together with drugs that can cause pirouette-type arrhythmias, for example, antiarrhythmics (quinidine, sotalol, hydroquinidine), some neuroleptics (pimozide, thioridazine), other drugs such as cisapride . Avoid the development of hypokalemia and, if necessary, carry out its correction. It is necessary to monitor the QT interval.

Amphotericin B (IV), gluco- and mineralocorticosteroids (for systemic administration), tetracosactide, laxatives stimulating intestinal motility increase the risk of hypokalemia (additive effect). It is necessary to control the level of potassium in the blood plasma, if necessary - its correction. Particular attention should be given to patients who simultaneously receive cardiac glycosides. Use laxatives that do not stimulate intestinal motility.

Hypokalemia increases the toxic effect of cardiac glycosides. With the simultaneous use of indapamide and cardiac glycosides, it is necessary to monitor the level of potassium in the blood plasma and the parameters of the ECG and, if necessary, adjust the therapy.

Combinations where caution is required

Diuretics (including indapamide) can cause functional renal failure, which increases the risk of developing lactic acidosis while taking metformin. Metformin should not be given if serum creatinine is greater than 1.5 mg / dL (135 μmol / L) in men and 1.2 mg / dL (110 μmol / L) in women.

With significant dehydration of the body, which is caused by the intake of diuretics, the risk of developing kidney failure increases with the use of iodine-containing contrast agents in high doses. Before using Iodine containing contrast agents, rehydration should be performed.

With simultaneous application with calcium salts, the development of hypercalcemia is possible as a result of a decrease in urinary excretion.

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

Analogues of Nolistral

Structural analogs for the active substance:

• Ko-Perineva;
• Noliprel A;
• Noliprel A Bee Fort;
• Noliprel A forte;
• Noliprel forte;
• Perindid;
• Perindopril-Indapamid Richter.

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