Noliprel A Forte tablets 5 mg + 1.25 mg 30 pcs. in Moscow

Noliprel A Forte tablets 5 mg + 1.25 mg 30 pcs. in Moscow

The use of Noliprel® 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.

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

Renal dysfunction

Therapy is contraindicated in patients with severe renal failure (creatinine clearance less than 30 ml/min). In some patients with 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 heart failure or underlying renal impairment, including stenosis of one or two renal arteries.

As a rule, the use of perindopril and indapamide is not recommended for patients with bilateral renal artery stenosis or stenosis of a single functioning kidney.

Arterial hypotension and water-electrolyte imbalance

Hyponatremia is associated with a risk of sudden development of arterial hypotension (especially in patients with stenosis of one or two renal arteries). 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® 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, 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. Perindopril should be used with extreme caution in patients with diffuse connective tissue diseases, while taking immunosuppressive drugs, allopurinol or procainamide, and with simultaneous exposure to these factors, especially in patients with underlying renal impairment. Some patients developed severe infections, in some cases resistant to intensive antibiotic therapy. When prescribing perindopril to such patients, it is recommended to periodically monitor the number of leukocytes in the blood. Patients should report any signs of infectious diseases (eg, sore throat, fever) to their doctor.

Hypersensitivity/angioedema (Quincke's edema)

When taking ACE inhibitors (including perindopril), in rare cases, the development of angioedema of the face, extremities, lips, tongue, glottis and/or larynx may occur. If symptoms appear, perindopril should be discontinued immediately and the patient should be observed until signs of edema completely disappear. If the swelling affects only the face and lips, it usually resolves on its own, although antihistamines may be used to treat symptoms.

Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, glottis, or larynx can lead to airway obstruction. If such symptoms appear, you should immediately administer epinephrine (adrenaline) subcutaneously at a dilution of 1:1000 (0.3 or 0.5 ml) and/or ensure airway patency.

Patients with a history of angioedema not associated with taking ACE inhibitors may have an increased risk of developing it when taking drugs of this group.

In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. In this case, patients experience abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and with normal levels of C-1 esterase. The diagnosis is made using computed tomography of the abdominal region, ultrasound, or at the time of surgery. Symptoms disappear after stopping ACE inhibitors. In patients with abdominal pain receiving ACE inhibitors, the possibility of developing angioedema of the intestine must be taken into account when making a differential diagnosis.

Anaphylactoid reactions during desensitization

There are isolated reports of the development of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with the venom of hymenoptera insects (bees, wasps). ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. Prescription of an ACE inhibitor should be avoided in patients receiving immunotherapy with hymenoptera venom. However, an anaphylactoid reaction can be avoided by temporarily discontinuing the ACE inhibitor at least 24 hours before the procedure.

Anaphylactoid reactions during LDL apheresis

In rare cases, life-threatening anaphylactoid reactions may occur in patients receiving ACE inhibitors during low-density lipoprotein (LDL) apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be temporarily discontinued before each apheresis procedure.

Hemodialysis

Anaphylactoid reactions have been reported in patients receiving ACE inhibitors during hemodialysis using high-flux membranes (eg, AN69). Therefore, it is advisable to use a different type of membrane or use an antihypertensive drug of a different pharmacotherapeutic group.

Potassium-sparing diuretics and potassium supplements

As a rule, the combined use of perindopril and potassium-sparing diuretics, as well as potassium preparations and potassium-containing table salt substitutes is not recommended.

Cough

During therapy with an ACE inhibitor, a dry cough may occur. The cough persists for a long time while taking drugs of this group and disappears after their discontinuation. If a patient develops a dry cough, one should be aware of the possible connection of this symptom with taking an ACE inhibitor. If the attending physician believes that ACE inhibitor therapy is necessary for the patient, the drug may be continued.

Use in pediatrics

Noliprel® should not be prescribed to children and adolescents under the age of 18 years due to the lack of data on the effectiveness and safety of the use of perindopril as monotherapy or as part of combination therapy in patients in this age group.

Risk of arterial hypotension and/or renal failure (in patients with heart failure, fluid and electrolyte imbalance, etc.)

In some pathological conditions, significant activation of the renin-angiotensin-aldosterone system may be observed, especially with severe hypovolemia and a decrease in the level of plasma electrolytes (against the background of a salt-free diet or long-term use of diuretics), in patients with initially low blood pressure, stenosis of one or two kidneys arteries, chronic heart failure or cirrhosis of the liver with the presence of edema and ascites.

The use of an ACE inhibitor causes a blockade of this system and therefore may be accompanied by a sharp decrease in blood pressure and/or an increase in plasma creatinine levels, indicating the development of functional renal failure. These phenomena are more often observed when taking the first dose of the drug or during the first two weeks of therapy. Sometimes these conditions develop acutely and during other periods of therapy. In such cases, when resuming therapy, it is recommended to use the drug at a lower dose and then gradually increase the dose.

Elderly patients

Before starting to take the drug, it is necessary 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 taking into account the degree of reduction in blood pressure, especially in the case of dehydration and loss of electrolytes. Such measures help to avoid a sharp decrease in blood pressure.

Atherosclerosis

The risk of arterial hypotension exists in all patients, however, special care should be taken when using the drug in patients with coronary heart disease and cerebrovascular insufficiency. In such patients, treatment should be started with low doses.

Patients with renovascular hypertension

The treatment method for renovascular hypertension is revascularization. However, the use of ACE inhibitors has a beneficial effect in patients both awaiting surgery and in cases where such surgery cannot be performed.

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

Other risk groups

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

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

Patients with diabetes mellitus

When prescribing the drug to patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, blood glucose levels must be carefully monitored during the first month of therapy.

Ethnic differences

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

Surgery/General anesthesia

The use of ACE inhibitors in patients undergoing surgery under general anesthesia can lead to a significant decrease in blood pressure, especially when using general anesthesia agents that have a hypotensive effect.

It is recommended to stop taking long-acting ACE inhibitors (including perindopril) 12 hours before surgery.

Aortic stenosis / Mitral stenosis / Hypertrophic cardiomyopathy

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

Liver failure

In rare cases, cholestatic jaundice occurs while taking ACE inhibitors. As this syndrome progresses, fulminant liver necrosis develops, sometimes with death. The mechanism of development of this syndrome is unclear. If jaundice or a significant increase in the activity of liver enzymes occurs while taking ACE inhibitors, you should stop taking the drug and consult a doctor.

Anemia

Anemia can develop in patients after kidney transplantation or in people on hemodialysis. In this case, the decrease in hemoglobin concentration is greater, the higher its initial value. This effect does not appear to be dose-dependent, but may be related to the mechanism of action of ACE inhibitors.

Hyperkalemia

Hyperkalemia may develop during treatment with ACE inhibitors, including perindopril. Risk factors for hyperkalemia include renal failure, decreased renal function, advanced age, diabetes mellitus, certain concomitant conditions (dehydration, acute decompensated heart failure, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), and potassium preparations or potassium-containing substitutes for table salt, as well as the use of other drugs that increase the level of potassium in the blood plasma (for example, heparin). The use of potassium supplements, potassium-sparing diuretics, and potassium-containing table salt substitutes can lead to a significant increase in potassium levels in the blood, especially in patients with reduced renal function. Hyperkalemia can cause serious, sometimes fatal, abnormal heart rhythms. If a combination of the above drugs is necessary, treatment should be carried out with caution, against the background of regular monitoring of potassium levels in the blood serum.

Indapamide

When thiazide and thiazide-like diuretics are prescribed to patients with impaired liver function, hepatic encephalopathy may develop. In this case, diuretics should be stopped immediately.

Photosensitivity

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

Content of sodium ions in blood plasma

Before starting treatment, it is necessary to determine the content of sodium ions in the blood plasma. While taking the drug, this indicator should be regularly monitored. All diuretics can cause hyponatremia, which sometimes leads to serious complications. Hyponatremia at the initial stage may not be accompanied by clinical symptoms, so regular laboratory monitoring is necessary. More frequent monitoring of sodium ion levels is indicated for patients with liver cirrhosis and the elderly.

Content of potassium ions in blood plasma

Therapy with thiazide and thiazide-like diuretics is associated with a risk of hypokalemia. Hypokalemia (less than 3.4 mmol/l) should be avoided in the following high-risk patients: elderly patients, debilitated patients or those receiving concomitant drug therapy, patients with liver cirrhosis, peripheral edema or ascites, coronary artery disease, heart failure. Hypokalemia in these patients enhances the toxic effect of cardiac glycosides and increases the risk of developing arrhythmias.

Patients with an increased QT interval are also at increased risk, and it does not matter whether this increase is caused by congenital causes or the effect of drugs.

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

If hypokalemia is detected, appropriate treatment should be prescribed.

Content of calcium ions in blood plasma

Thiazide and thiazide-like diuretics reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in the concentration of calcium in the blood plasma. Severe hypercalcemia may be a consequence of previously undiagnosed hyperparathyroidism. Before studying the function of the parathyroid gland, you should stop taking diuretic drugs.

Plasma glucose levels

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

Uric acid

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

Diuretics and kidney function

Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (plasma creatinine in adults below 25 mg/l or 220 µmol/l). In elderly patients, creatinine clearance is calculated taking into account age, body weight and gender.

At the beginning of treatment with diuretics, patients due to hypovolemia and hyponatremia may experience a temporary decrease 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, but its severity may increase in patients with renal failure.

Athletes

Indapamide may give a positive reaction during doping control.

Impact on the ability to drive vehicles and machinery

The action of the substances included in the drug Noliprel® does not lead to impairment of psychomotor reactions. However, some patients may develop different individual reactions in response to a decrease in blood pressure, especially at the beginning of therapy or when other antihypertensive drugs are added to the therapy. In this case, the ability to drive a car or operate other machinery may be reduced.

Compound

The drug Noliprel is offered in several different forms. All variations of the drug include perindopril and indapamide . Combined Noliprel contain 2 mg of perindopril and 0.625 mg of indapamide. The composition of 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. Noliprel A Forte tablets contain 5 mg of perindopril and 1.25 mg of indapamide. Noliprel A Bi-forte contains 10 mg of perindopril and 2.5 mg of indapamide.

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

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. Blood pressure decreases in people with different levels of renin . 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.

Overdose

In case of an overdose of the drug, there is a severe decrease in blood pressure, nausea, vomiting, dizziness , mood instability, symptoms of renal failure, and electrolyte imbalance. In this case, you need to immediately bring the water-electrolyte balance back to normal, rinse the stomach, and take enterosorbents. Noliprel metabolites can be removed using dialysis. If necessary, intravenous saline is administered.

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.

Indapamide is completely and relatively quickly absorbed from the gastrointestinal tract. The maximum concentration of the substance in plasma is observed one hour after oral administration.

The substance binds to plasma proteins by 79%. Half-life is 19 hours. The substance is excreted in the form of inactive metabolites by the kidneys (approximately 70%) and intestines (approximately 22%). In people with renal failure, no changes in the pharmacokinetics of the substance are observed.

Instructions for use of Noliprel (Method and dosage)

It is advisable to take Noliprel tablets in the morning. The medicine is prescribed one tablet per day. The instructions for Noliprel Forte provide for a similar treatment regimen. Noliprel A and Noliprel A Bi Forte are prescribed to patients 1 tablet per day. If patients have creatinine clearance equal to or greater than 30 ml/min, then there is no need to reduce the dose. If clearance equals or exceeds 60 ml per day, then during treatment it is necessary to carefully monitor the level of potassium and creatinine in the blood.

If necessary, after several months of treatment, the doctor may increase the dose by prescribing Noliprel A Forte or another type of this drug instead of Noliprel.

Contraindications

Contraindications to the use of all types of the drug Noliprel are the following diseases and conditions:

• high sensitivity to the components of the drug or the presence of allergic reactions to its components;
• renal failure , in which creatinine clearance is less than 30 ml/min;
• liver failure , in which there is a tendency to encephalopathy ;
• combination with drugs that prolong the QT interval, as well as antiarrhythmic drugs;
• hypokalemia;
• renal artery stenosis;
• lactase deficiency, glucose-galactose malabsorption syndrome, galactosemia;
• history of angioedema;
• pregnancy , lactation ;
• age up to eighteen years.

Also, you should not take the drug at the same time as potassium supplements or potassium-sparing diuretics if the patient has hyperkalemia.

Due to the lack of sufficient information, it is not recommended to use the tablets for treatment in people who are on hemodialysis , as well as in patients with decompensated heart failure.

It is prescribed with caution to people with systemic connective tissue diseases, those taking antidepressants, and suppression of bone marrow hematopoiesis. angina pectoris are also treated with caution .

Interaction

Noliprel should not be taken at the same time as lithium medications. If it is impossible to discontinue one of the drugs, the lithium level in the blood should be closely monitored.

With simultaneous treatment with potassium-sparing diuretics or drugs with potassium, the concentration of potassium in the blood may increase. This combination is recommended only for hypokalemia.

When indapamide with vincamine, bepridil, sultopride, halofantrine, as well as with simultaneous intravenous administration of erythromycin , arrhythmia and bradycardia may occur.

Sometimes, with simultaneous treatment with Insulin and Noliprel, hypoglycemia may develop.

When taking non-steroidal anti-inflammatory drugs, the antihypertensive properties of Noliprel are inhibited. If you are dehydrated, this combination of medications can cause kidney problems or kidney failure.

When treated with Noliprel and antipsychotics or tricyclic antidepressants, orthostatic hypotension may develop.

Due to the retention of water and electrolytes in the body, with simultaneous treatment with Noliprel and mineralocorticoids, glucocorticosteroids, stimulant laxatives, tetracosactide, amphotericin B, the hypotensive effect is reduced and the likelihood of hypokalemia increases.

Due to the possibility of developing hypokalemia, the risk of toxic effects of cardiac glycosides increases.

When combined with Metformin, acidosis may develop .

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.

Concomitant treatment with cyclosporine may increase blood creatinine levels.

Side effects

• In the functions of the cardiovascular system : severe hypotension, orthostatic collapse, in rare cases: arrhythmia , stroke , myocardial infarction .
• In the functions of the genitourinary system : deterioration of kidney function, proteinuria in people with glomerular nephropathy, in rare cases - acute renal failure. There may be a decrease in potency.
• In the functions of the central and peripheral nervous system : severe fatigue, dizziness , headache , asthenia, unstable mood, impaired hearing, vision, decreased appetite, convulsions, and in some cases, stupor.
• In the functions of the respiratory system : cough, difficulty breathing, bronchospasm, nasal discharge.
• In the functions of the gastrointestinal tract : dyspepsia, abdominal pain, pancreatitis , cholestasis, increased transaminase activity, hyperbilirubinemia.
• In the functions of the blood system : against the background of hemodialysis or after a kidney transplant, patients may develop anemia, in rare cases - thrombocytopenia, pancytopenia, agranulocytosis, hemolytic anemia.
• Allergic manifestations : skin itching, rash, swelling, urticaria.
• Patients with liver failure may develop hepatic encephalopathy. People with impaired water-electrolyte balance may experience hyponatremia, hypovolemia, hypokalemia, and dehydration.

special instructions

People who have been prescribed treatment with Noliprel need adequate dehydration of the body to prevent a sharp decrease in blood pressure.

People with heart failure may be treated with beta blockers at the same time.

When treated with Noliprel, a positive reaction is observed during a doping test.

In the first weeks of treatment, it is important to drive vehicles or operate precision machinery carefully when treating with Noliprel.

If during treatment there is a significant decrease in pressure, it may be necessary to administer 0.9% sodium chloride intravenously.

Treatment of patients with cerebral circulatory insufficiency or coronary heart disease should begin with small doses of Noliprel.

In people who have very high levels of uric acid in the blood, when treated with varieties of the drug Noliprel, the risk of developing gout .