Noliprel instructions for use. Instructions for use of the drug noliprel - indications for use, side effects, dosage and analogues. Use during pregnancy and lactation

Noliprel is a combined antihypertensive agent.

Release form and composition

Dosage form - tablets: oblong, white, with a dividing line on both sides (14 or 30 pieces in blisters packed in a sachet, in a carton pack 1 sachet).

• Perindopril erbumine (perindopril tertbutylamine) - 2 mg, which is equivalent to 1.669 mg of perindopril base;
• Indapamide - 0.625 mg.

Auxiliary components: microcrystalline cellulose, anhydrous colloidal silicon dioxide, magnesium stearate, lactose monohydrate.

Pharmacological properties

Noliprel is a combined drug, which includes indapamide (a diuretic belonging to the group of sulfonamide derivatives) and perindopril (an angiotensin-converting enzyme inhibitor). Its pharmacological properties are a combination of the individual properties of each of the components. The combination of indapamide and perindopril provides an enhancement of the action of each of them.

Pharmacodynamics

Noliprel has a dose-dependent hypotensive effect, affecting both systolic and diastolic blood pressure in the supine or standing position. The antihypertensive effect of the drug is prolonged and persists for 1 day. The therapeutic effect is observed less than 1 month after the start of treatment and is not accompanied by tachycardia. Cancellation of Noliprel does not provoke the development of withdrawal syndrome. Indapamide and perindopril are characterized by a synergistic hypotensive effect compared with monotherapy with these drugs.

The drug reduces the degree of left ventricular hypertrophy, increases the elasticity of arteries, helps to reduce total peripheral vascular resistance and does not affect lipid metabolism (low-density lipoprotein cholesterol (LDL) and high density lipoprotein (HDL), total cholesterol, triglycerides).

The effect of Noliprel on cardiovascular morbidity and mortality is not well understood.

Perindopril

Perindopril is an inhibitor of the enzyme responsible for the conversion of angiotensin I to angiotensin II (ACE inhibitor). Kinase (angiotensin-converting enzyme) is an exopeptidase that carries out both the conversion of angiotensin I to the vasoconstrictor compound angiotensin II and the destruction of bradykinin, which is characterized by a vasodilating effect, with the formation of an inactive heptapeptide.

As a result, perindopril reduces the production of aldosterone, in accordance with the principle of negative feedback increases the activity of renin in the blood plasma and, with long-term therapy, lowers the total peripheral vascular resistance, which is caused mainly by the effect on the vessels localized in the kidneys and muscles.

These effects are not accompanied by the occurrence of reflex tachycardia or salt and fluid retention.

Perindopril normalizes the functioning of the myocardium, reducing preload and afterload.

Studies of hemodynamic parameters in patients with chronic heart failure revealed that this substance increases muscle peripheral blood flow, increases cardiac output and increases cardiac index, reduces filling pressure in both ventricles of the heart and reduces total peripheral vascular resistance.

Perindopril is effective in the treatment of arterial hypertension of varying severity. The antihypertensive effect of the drug reaches a peak 4-6 hours after a single dose and lasts 24 hours. 1 day after the use of Noliprel, a pronounced (about 80%) inhibition of ACE of a residual nature is noted.

Perindopril has an antihypertensive effect in patients with both reduced and normal plasma renin activity. The compound is characterized by a vasodilating effect, provides regeneration of the structure of the vascular wall of small arteries and restoration of elasticity of large arteries, and also minimizes left ventricular hypertrophy.

The combination of Noliprel with thiazide diuretics makes the antihypertensive effect more pronounced. Also, the simultaneous use of a thiazide diuretic and an ACE inhibitor reduces the risk of hypokalemia during the appointment of diuretics.

Indapamide

Indapamide is a member of the sulfonamide group and is similar in its pharmacological characteristics to thiazide diuretics. The substance slows down the reabsorption of sodium ions in the cortical element of the loop of Henle, which leads to a more intense excretion through the kidneys of chloride, sodium ions and, to a lesser extent, magnesium and potassium ions. This increases diuresis and reduces blood pressure.

Indapamide as a monotherapy drug has an antihypertensive effect lasting 24 hours. It becomes noticeable when taking the drug in doses that have a minimal diuretic effect. The compound improves the elastic properties of large arteries, reduces total peripheral vascular resistance and reduces left ventricular hypertrophy.

At a certain dose of indapamide, thiazide and thiazide-like diuretics reach a plateau of therapeutic effect, while the frequency side effects continues to increase with a further increase in the dose of the drug. Therefore, an increase in the dose of indapamide is not justified if there is no therapeutic effect when taking the recommended dose.

Indapamide does not change the concentration of lipids (triglycerides, LDL, HDL, cholesterol) and carbohydrate metabolism (including in patients with concomitant diabetes mellitus).

Pharmacokinetics

With the combined use of indapamide and perindopril, their pharmacokinetic parameters do not change compared with the separate intake of these drugs.

Perindopril

When taken orally, perindopril is absorbed at a significant rate. Its maximum content in blood plasma is recorded 1 hour after ingestion. The half-life of the substance from the blood plasma is 1 hour. Pharmacological activity is not typical for perindopril. Approximately 27% of the ingested dose enters the bloodstream after conversion to the active metabolite perindoprilat. In addition to perindoprilat, 5 more metabolites are formed that do not show pharmacological activity. The maximum content of perindoprilat in plasma is observed 3-4 hours after oral administration. Food intake inhibits the transition of perindopril to perindoprilat, affecting its bioavailability. Therefore, the drug should be taken once a day, in the morning and on an empty stomach.

A linear dependence of the content of perindopril in blood plasma on its dose was revealed. The volume of distribution of unbound perindoprilat is about 0.2 l/kg. Perindoprilat binds to plasma proteins, mainly to ACE, and the degree of binding is determined by the level of perindopril in the blood and is approximately 20%.

Perindoprilat is excreted from the body in the urine. Effective period The half-life is approximately 17 hours, so steady-state concentrations are reached within 4 days.

Removal of perindoprilat slows down in elderly patients, as well as in patients with renal and heart failure. The dialysis clearance of perindoprilat is 70 ml/min. The pharmacokinetics of perindopril changes in patients with cirrhosis of the liver: the hepatic clearance of the compound is reduced by 2 times. However, the amount of perindoprilat formed does not tend to decrease, so dose adjustment is not necessary.

Indapamide

Indapamide is rapidly and completely absorbed from the gastrointestinal tract. The maximum level of the compound in blood plasma is recorded 1 hour after oral administration.

Indapamide binds to plasma proteins by 79%. The half-life is 14-24 hours (mean -18 hours). Repeated administration of the drug does not cause its accumulation in the tissues of the body. Indapamide is excreted mainly through the kidneys (70% of the dose) and through the intestines (22% of the dose) as inactive metabolites. Renal insufficiency does not affect the pharmacokinetics of the compound.

Indications for use

The use of Noliprel is indicated for the treatment of essential arterial hypertension.

Contraindications

• Chronic heart failure in the stage of decompensation in untreated patients;
• hypokalemia;
• Increased content of potassium in the blood plasma;
• Angioedema (Quincke's edema) in history;
• Idiopathic or hereditary angioedema;
• Severe renal (creatinine clearance (CC) less than 30 ml / min) and / or hepatic (including encephalopathy) insufficiency;
• Syndrome of glucose-galactose malabsorption, lactase deficiency, galactosemia;
• Simultaneous use of potassium-sparing diuretics, potassium and lithium preparations, antiarrhythmic drugs (risk of developing pirouette-type arrhythmia), drugs that prolong the QT interval;
• period of pregnancy and breastfeeding;
• Age up to 18 years;
• Hypersensitivity to angiotensin-converting enzyme (ACE) inhibitors and sulfonamides;
• Hypersensitivity to the components of the drug.

Noliprel is also contraindicated in patients on hemodialysis.

The drug should be administered with caution when systemic diseases connective tissue (including systemic lupus erythematosus, scleroderma), suppression of bone marrow hematopoiesis, treatment with immunosuppressants (due to the risk of developing agranulocytosis, neutropenia), reduced blood volume (against the background of taking diuretics, salt-free diet, vomiting, diarrhea), cerebrovascular diseases, renovascular hypertension, diabetes mellitus, angina pectoris, aortic valve stenosis, hypertrophic cardiomyopathy, chronic heart failure functional class IV (according to NYHA classification), hyperuricemia (especially accompanied by urate nephrolithiasis and gout), hemodialysis using high-flow membranes, lability of blood pressure (BP); in the period after kidney transplantation; elderly patients.

Instructions for use Noliprel: method and dosage

Noliprel is taken orally, preferably before breakfast.

The appointment of the drug in elderly patients should be made on the basis of data on the level of potassium concentration in the blood plasma and the functional activity of the kidneys. Treatment should begin with individual dose selection, taking into account the degree of reduction in blood pressure, especially in patients with dehydration and loss of electrolytes. Treatment should begin with 1 tablet 1 time per day.

In patients with moderate renal insufficiency (CC 30-60 ml / min), the daily dose should not exceed 1 tablet, with CC 60 ml / min and above, dose adjustment is not required. Treatment must be accompanied by monitoring the level of potassium and creatinine in the blood plasma (after two weeks of therapy and then 1 time in 2 months).

If laboratory signs of functional renal failure appear during the use of Noliprel, the drug should be discontinued. Combination treatment should be resumed only with the use of low doses of the drug or in monotherapy. Patients with underlying renal impairment, including renal artery stenosis and severe heart failure, are at risk of developing renal failure.

Dose adjustment is not required in patients with moderate hepatic impairment.

Side effects

• General disorders: often - asthenia; infrequently - sweating;
• Cardiovascular system: infrequently - a strong decrease in blood pressure, including orthostatic hypotension; very rarely - bradycardia, atrial fibrillation, ventricular tachycardia, angina pectoris, myocardial infarction and other cardiac arrhythmias;
• Lymphatic and circulatory system: very rarely - leukopenia or neutropenia, thrombocytopenia, agranulocytosis, hemolytic anemia, aplastic anemia; in patients after kidney transplantation who are on hemodialysis, anemia may develop;
• Digestive system: often - dry mouth, constipation, diarrhea, nausea, abdominal pain, vomiting, epigastric pain, loss of appetite, impaired taste perception, dyspepsia; rarely - cholestatic jaundice, angioedema of the intestine; very rarely - pancreatitis; possibly - hepatic encephalopathy (in patients with liver failure);
• Organ of vision: often - visual impairment;
• Organ of hearing: often - tinnitus;
• Nervous system: often - headache, paresthesia, asthenia, dizziness; infrequently - mood lability, sleep disturbance; very rarely - confusion;
• Respiratory system: often - transient dry cough, shortness of breath; infrequently - bronchospasm; very rarely - rhinitis, eosinophilic pneumonia;
• Musculoskeletal system and connective tissues: often - muscle spasms;
• Reproductive system: infrequently - impotence;
• Urinary system: infrequently - renal failure; very rarely - acute renal failure;
• Dermatological and allergic reactions: often - skin rash, itching, maculopapular rash; infrequently - urticaria, angioedema of the larynx and / or glottis, mucous membranes of the tongue, lips, face, limbs, hypersensitivity reactions (often skin, in predisposed patients), hemorrhagic vasculitis; exacerbation of disseminated lupus erythematosus; very rarely - toxic epidermal necrolysis, erythema multiforme, Steven-Jones syndrome, photosensitivity reactions;
• Laboratory indicators: hypovolemia and hyponatremia, hypokalemia, transient increase in blood glucose and uric acid levels, transient hyperkalemia, a slight increase in plasma creatinine and urea levels (more often with renal artery stenosis, renal failure, against the background of arterial hypertension therapy with diuretics); rarely - hypercalcemia.

Overdose

When taking high doses of Noliprel, the most common symptom of an overdose is a pronounced decrease in blood pressure, sometimes combined with drowsiness, dizziness, clouded consciousness, convulsions, nausea, vomiting and oliguria, which can turn into anuria (due to hypovolemia). Also, electrolyte disorders often develop: hypokalemia or hyponatremia.

Emergency care consists in removing Noliprel from the body by gastric lavage and / or prescribing activated carbon, accompanied by subsequent normalization of the water-electrolyte balance. With a significant decrease in blood pressure, the patient is placed in a supine position, lifting his legs. If necessary, hypovolemia is corrected (for example, by intravenous infusion of 0.9% sodium chloride solution). Perindoprilat, the active metabolite of perindopril, is effectively removed from the body by dialysis.

special instructions

At the beginning of therapy, careful monitoring of patients who have not previously taken two antihypertensive drugs (perindopril, indapamide) at the same time is required, since the risk of idiosyncrasy increases.

Since hyponatremia can cause sudden development of arterial hypotension, regular monitoring of the level of electrolyte concentration in the blood plasma is required, especially in patients with renal artery stenosis after vomiting or diarrhea. To restore the water and electrolyte balance, intravenous administration of a 0.9% sodium chloride solution is recommended. Therapy can be continued after normalization of blood pressure and blood volume, using a low dose of the drug or switching to monotherapy.

Treatment should be accompanied by regular monitoring of the level of potassium in the blood plasma.

The risk of developing neutropenia during the use of the drug increases in patients with a functional disorder of the kidneys, more often with scleroderma, systemic lupus erythematosus. Symptoms of neutropenia are dose-dependent.

With concomitant therapy with immunosuppressive agents in patients with diffuse connective tissue pathologies, the level of leukocytes in the blood should be monitored. When symptoms of angina, fever and other infectious diseases you need to see a doctor.

If there are signs of hypersensitivity to the drug in the form of angioedema, the drug should be immediately canceled and the patient should be prescribed appropriate therapy. In case of swelling of the tongue, larynx or glottis, it is recommended to secure the airway and immediately inject epinephrine (adrenaline) subcutaneously.

When conducting a differential diagnosis in patients with pain in the abdomen, the possibility of developing angioedema of the intestine should be considered.

Simultaneous administration with immunotherapy with hymenoptera venom is not recommended (in order to prevent the development of an anaphylactoid reaction, Noliprel should be temporarily discontinued 24 hours before the start of the desensitization procedure).

There is a risk of anaphylactoid reactions during low-density lipoprotein (LDL) apheresis using dextran sulfate, and the drug must be stopped before each apheresis procedure.

Taking pills can cause a dry cough in a patient.

To avoid a sharp drop in blood pressure, treatment should be started with low doses of the drug and then gradually increased, taking into account tolerability and laboratory parameters of plasma creatinine levels.

Treatment of patients with ischemic disease heart failure and cerebral circulation should start at low doses.

With renovascular hypertension, the use of the drug should be started only in a hospital with low doses with regular monitoring of kidney function and potassium content in the blood plasma.

In arterial hypertension and coronary heart disease, the drug should be used together with beta-blockers.

Treatment of patients with diabetes mellitus who are on insulin or oral hypoglycemic agents during the first month should be accompanied by regular monitoring of blood glucose levels, especially with hypokalemia.

With a planned surgical intervention, the drug is stopped 12 hours before the start of general anesthesia.

In case of a significant increase in the activity of liver enzymes or the appearance of jaundice, the use of Noliprel should be discontinued.

Anemia may develop in patients on hemodialysis or after kidney transplantation.

With the development of hepatic encephalopathy, the use of diuretics should be discontinued.

Avoid exposure to direct sunlight and ultraviolet radiation. With the development of photosensitivity reactions during treatment with the drug, it should be discontinued.

Before starting the use of the drug and during the period of treatment, it is necessary to regularly determine the level of concentration of sodium ions in the blood plasma, especially in elderly patients and patients with cirrhosis of the liver.

The risk of developing hypokalemia during the use of Noliprel is most susceptible to elderly patients, malnourished patients who are on concomitant drug treatment, patients with cirrhosis of the liver, peripheral edema or ascites, with an increased QT interval, heart failure, coronary heart disease. In this category of patients, hypokalemia contributes to the appearance of severe cardiac arrhythmias, so they need to ensure regular monitoring of the level of potassium ions in the blood plasma from the first week of treatment.

An increase in the level of uric acid in the blood plasma increases the risk of gout attacks.

Before conducting a study of the function of the parathyroid gland, it is necessary to stop taking diuretics.

When conducting a doping control, Noliprel may give a positive reaction.

During the period of use of the drug, patients should be careful when driving vehicles and mechanisms.

Use during pregnancy and lactation

According to the instructions, Noliprel is not recommended during pregnancy. Its reception in the first trimester is strictly prohibited. Planning for pregnancy or its occurrence during drug therapy is a direct indication for discontinuation of the drug and the selection of another regimen antihypertensive therapy. Appropriate controlled studies of ACE inhibitors in pregnant women have not been conducted. There are limited data on the effects of Noliprel in the first trimester of pregnancy, indicating that treatment with it did not increase the risk of malformations due to fetotoxicity.

The effect of the drug on the fetus for a long period of time in the II and III trimesters of pregnancy can cause developmental disorders (delayed ossification of the skull bones, oligohydramnios, decreased renal function) and provoke complications in the newborn (hyperkalemia, arterial hypotension, renal failure).

Long-term use of thiazide diuretics in the third trimester of pregnancy can cause hypovolemia in the mother, as well as deterioration of uteroplacental blood flow, which causes fetoplacental ischemia and fetal growth retardation. Occasionally, during treatment with diuretics, shortly before the onset of labor, newborns experience thrombocytopenia and hypoglycemia.

If a woman took Noliprel during the II or III trimester of pregnancy, it is necessary to conduct an ultrasound examination of the fetus to assess kidney function and the condition of the bones of the skull.

The period of lactation is a contraindication to the appointment of the drug. Information about the possible penetration of perindopril into breast milk is not considered reliable. Indapamide passes into breast milk. Taking thiazide diuretics can lead to suppression of lactation or a decrease in breast milk production. At the same time, the child sometimes develops increased sensitivity to sulfonamide derivatives, nuclear jaundice and hypokalemia.

Since the appointment of Noliprel during lactation can cause severe complications in an infant, it is recommended to carefully weigh the significance of therapy for the mother and decide whether to stop breastfeeding or discontinue the drug.

drug interaction

The safety of the simultaneous appointment of Noliprel with other drugs can only be determined by the attending physician, taking into account the patient's condition and comorbidities.

Analogues

The analogues of Noliprel are: Co-prenesa, Prestarium, Ko-perineva, Perindopril-Indapamid Richter, Noliprel A Bi-forte.

Terms and conditions of storage

Keep out of the reach of children at room temperature.

Shelf life - 3 years, after opening the sachet - 2 months.