Instructions for use PRESTANCE

pharmachologic effect

Manufacturer: SERVIER INDUSTRY LABORATORIES (France)
Release form: tablets

Active ingredient: perindopril, amlodipine

Analogs: Prestarium, Dalneva, Noliprel

Prestance is a combination drug in which the successful combination of the active substances perindopril with amlodipine ensures normalization of blood pressure in hypertension of any severity. This occurs due to stimulation of peripheral and increased renal blood flow, increased elasticity of the vascular wall of large and small arteries, and the transition of calcium ions into cardiomyocytes. These processes occur without changes in the number of heart contractions and glomerular filtration rate.

The medication effectively lowers both systolic and diastolic blood pressure in a fairly short time. Normalization of its indicators is achieved after a month of taking the medicine. Abrupt cessation of Prestance use does not lead to withdrawal syndrome and a return to high blood pressure levels.

Prestance®

Special instructions regarding perindopril and amlodipine also apply to the drug Prestance®.

Perindopril

Hypersensitivity/angioedema

When taking ACE inhibitors, including perindopril, in rare cases, the development of angioedema of the face, extremities, lips, mucous membranes, tongue, vocal folds and/or larynx may occur (see section “Side effects”). This can happen at any time during therapy. If symptoms appear, the drug should be stopped immediately and the patient should be observed until then. until signs of swelling disappear completely. 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, vocal folds, or larynx can lead to airway obstruction. If such symptoms occur, epinephrine (adrenaline) should be immediately administered subcutaneously and/or the airway should be secured. The patient should be under medical supervision until symptoms disappear completely and permanently.

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 (see section "Contraindications").

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 or vomiting, in some cases, without previous angioedema of the face and with normal C1-esterase levels. The diagnosis is made using computed tomography of the abdominal region, ultrasound, or at the time of surgery. Symptoms disappear after stopping ACE inhibitors. Therefore, in patients with abdominal pain receiving ACE inhibitors. when carrying out differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine (see section “Side effects”).

Combined use with combination drugs containing valsartan + sacubitril

The combined use of perindopril with combination drugs containing valsartan + sacubitril is contraindicated, as the risk of developing angioedema is increased (see section "Contraindications"). The use of a combination drug containing valsartan + sacubitril is possible no earlier than 36 hours after the last dose of perindopril. The use of perindopril is possible no earlier than 36 hours after stopping the combination drug containing valsartan + sacubitril (see sections “Contraindications” and “Interaction with other drugs”). When ACE inhibitors are used together with other neprilysin inhibitors (for example, racecadotril), the risk of developing angioedema may be increased (see section "Interaction with other drugs"). In patients receiving perindopril, a careful risk/benefit assessment should be performed before initiating treatment with enkephalinase inhibitors (eg, racecadotril).

Concomitant use with mTOR inhibitors (for example, sirolimus, everolimus, temsirolimus)

When used together with mTOR inhibitors (for example, sirolimus, everolimus, temsirolimus), the risk of developing angioedema (for example, swelling of the airways or tongue with or without impairment of respiratory function) may increase (see section "Interactions with other drugs").

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.

Anaphylactoid reactions during desensitization

There are isolated reports of the development of anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy (for example, hymenoptera venom). In these same patients, an anaphylactoid reaction was avoided by temporarily discontinuing ACE inhibitors, and if the drug was accidentally taken, the anaphylactoid reaction occurred again.

Neutropenia/agaranulocytosis/thrombocytopenia/anemia

There are reports of the development of neutropenia/agranulocytosis. thrombocytopenia and anemia while taking ACE inhibitors. In patients with normal renal function and in the absence of other concomitant factors, neutropenia rarely develops. Perindopril should be used with extreme caution against the background of systemic connective tissue diseases, as well as while taking immunosuppressants, allopurinol or procainamide, especially in patients with impaired renal function.

Some patients developed severe infectious diseases, in some cases resistant to intensive antibiotic therapy. When using perindopril in such patients, it is recommended to periodically monitor leukocytes in the blood. Patients should report any signs of infectious diseases (eg, sore throat, fever) to their doctor.

Renovascular hypertension

In patients with bilateral renal artery stenosis or arterial stenosis of a single functioning kidney, the risk of developing arterial hypotension and renal failure increases during therapy with ACE inhibitors. Taking diuretics may be an additional risk factor (see section "Contraindications"). Deterioration of renal function can be observed with even a slight change in serum creatinine concentration, even in patients with unilateral renal artery stenosis.

Double blockade of the RAAS

There is evidence of an increased risk of arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure) when ACE inhibitors are used together with ARB II or aliskiren. Therefore, double blockade of the RAAS through the combined use of ACE inhibitors with angiotensin II receptor antagonists or aliskiren is not recommended (see sections “Pharmacodynamics” and “Interaction with other drugs”). If a double blockade is absolutely necessary, it should be performed under the strict supervision of a specialist with regular monitoring of kidney function, blood electrolyte concentrations and blood pressure.

The use of ACE inhibitors in combination with angiotensin II receptor antagonists is contraindicated in patients with diabetic nephropathy and is not recommended in other patients (see sections “Contraindications” and “Interaction with other drugs”).

Primary hyperaldosteronism

Patients with primary hyperaldosteronism are usually not susceptible to antihypertensive drugs that act by inhibiting the RAAS. Therefore, the use of the drug in such patients is not recommended.

Arterial hypotension

ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic hypotension rarely develops in patients without concomitant diseases. The risk of excessive reduction in blood pressure is increased in patients with reduced circulating blood volume, which can be observed during diuretic therapy, while following a strict salt-free diet, hemodialysis, diarrhea and vomiting, as well as in patients with severe arterial hypertension with high renin activity (see sections “Side effects” and “Interaction with other drugs”). In patients at increased risk of developing symptomatic arterial hypotension, blood pressure, renal function and serum potassium levels should be carefully monitored during therapy with Prestance.

A similar approach is also used in patients with angina pectoris and cerebrovascular diseases, in whom severe arterial hypotension can lead to myocardial infarction or cerebrovascular accident.

If arterial hypotension develops, the patient should be transferred to the supine position with legs elevated. If necessary, the volume of circulating blood should be replenished with intravenous administration of 0.9% sodium chloride solution. Transient arterial hypotension is not an obstacle to further taking the drug. After restoration of circulating blood volume and blood pressure, treatment can be continued.

Mitral stenosis/aortic stenosis/hypertrophic cardiomyopathy

Perindopril, like other ACE inhibitors, should be administered with caution to patients with left ventricular outflow tract obstruction (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as to patients with mitral stenosis.

Renal dysfunction

For patients with renal failure (creatinine clearance < 60 ml/min), individual selection of doses of perindopril and amlodipine is recommended (see section “Dosage and Administration”). Such patients require regular monitoring of potassium and creatinine levels in the blood serum (see section “Side Effects”).

In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney during therapy with ACE inhibitors, an increase in the concentration of urea and creatinine in the blood serum is possible, which usually resolves when therapy is discontinued. This effect is most often observed in patients with renal failure. The additional presence of renovascular hypertension causes an increased risk of severe hypotension and renal failure in such patients.

In some patients with arterial hypertension without signs of renal vascular damage, an increase in the concentration of urea and creatinine in the blood serum is possible, especially when perindopril is co-administered with a diuretic, usually slight and transient. This effect is more often observed in patients with pre-existing renal impairment.

Liver failure

In rare cases, cholestatic jaundice occurs while taking ACE inhibitors. As this syndrome progresses, fulminant liver necrosis may develop, 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 (see section “Side Effects”) and be under appropriate medical supervision.

Ethnic differences

In patients of the Negroid race, angioedema develops more often than in representatives of other races while taking ACE inhibitors.

Perindopril, like other ACE inhibitors, may have a less pronounced antihypertensive effect in patients of the Black race compared to representatives of other races. This difference may be due to the fact that black patients with arterial hypertension are more likely to have low renin activity.

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. This should be taken into account when carrying out the differential diagnosis of cough.

Surgery/general anesthesia

In patients who are planning to undergo major surgery or use anesthetic agents that cause arterial hypotension, the use of perindopril may block the formation of angiotensin II against the background of compensatory release of renin. Treatment should be stopped one day before surgery. If arterial hypotension develops according to this mechanism, blood pressure should be maintained by replenishing blood volume.

Hyperkalemia

Hyperkalemia may develop during treatment with ACE inhibitors. including perindopril. Risk factors for hyperkalemia include renal failure, deterioration of renal function, age over 70 years, diabetes mellitus, certain concomitant conditions (dehydration, acute decompensation of chronic heart failure, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, or amiloride). ), as well as potassium preparations or potassium-containing salt substitutes, as well as the use of other drugs that increase the level of potassium in the blood plasma (for example, heparin, co-trimoxazole, also known as the combination of sulfamethoxazole + trimethoprim). 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 the combined use of perindopril and the above drugs is necessary, treatment should be carried out with caution against the background of regular monitoring of the content of potassium ions in the blood serum (see section “Interaction with other drugs”).

Patients with diabetes mellitus

When prescribing the drug to patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, during the first month of therapy it is necessary to carefully monitor the concentration of glucose in the blood (see section “Interaction with other drugs”).

Amlodipine

The effectiveness and safety of amlodipine in hypertensive crisis has not been established.

Heart failure

Patients with heart failure should be treated with caution.

When using amlodipine in patients with chronic heart failure of functional class III and IV according to the NYHA classification, pulmonary edema may develop. Slow calcium channel blockers, including amlodipine, should be used with caution in patients with congestive heart failure due to a possible increased risk of cardiovascular adverse events and mortality.

Liver failure

In patients with impaired liver function, T1/2 and AUC of amlodipine are increased. Recommendations for dosing of the drug have not been established. Taking amlodipine should be started with the lowest doses and precautions should be taken both at the beginning of treatment and when increasing the dose. In patients with severe hepatic impairment, the dose should be increased gradually, ensuring careful monitoring of the clinical condition.

Elderly patients

In elderly patients, increasing the dose should be done with caution (see sections “Pharmacokinetics” and “Dosage and Administration”).

Kidney failure

Patients with renal failure can take amlodipine in standard doses. Changes in plasma concentrations of amlodipine do not correlate with the degree of renal failure. Amlodipine is not excreted from the body by dialysis.

Prestance®

Special instructions regarding amlodipine and perindopril also apply to the drug Prestance®.

Excipients

Due to the presence of lactose in the drug, it is contraindicated to prescribe the drug to patients with hereditary galactose intolerance, complete lactase deficiency and glucose-galactose malabsorption.

Drug interactions

The combined use of the drug Prestance® with lithium preparations, potassium-sparing diuretics, potassium-containing substitutes or dantrolene is not recommended (see section “Interaction with other drugs”).

Analogues of Prestans

The Russian and foreign pharmacological industry produces a sufficient number of analogues of blood pressure tablets, which are similar in various respects to the original drug. These medications are sold by the pharmacy chain in the form of: generics, synonyms, and combination drugs.

Table of Prestansa analogues with price and country of origin

The price of Prestance analogues varies widely and depends on the manufacturer, the purity of the raw materials, and the amount of ingredients in the preparation. There are expensive and less expensive drugs, but with a high therapeutic effect. The selection of an antihypertensive drug will be made strictly by the doctor on an individual basis, taking into account all the characteristics of the patient.

What other drugs would justify replacing Prestance with analogues with an equivalent therapeutic effect? The list can be supplemented with the following medications:

• Losartan;
• Edarby Clo;
• Dalneva Co.;
• Valsacor;
• Bisoprolol;
• Noliprel fote;
• Nebilet;
• Perindopril;
• Triplix.

In this list of medications there are cheaper and more expensive analogues of Prestance, which give good results in reducing high blood pressure and improving the function of the heart muscle.

Prestans or Prestarium

Manufacturer: SERVIER INDUSTRIES LTD (Ireland)
Release form: tablets

Active ingredient: perindopril

Both drugs effectively reduce blood pressure in hypertension. The difference between the medications is that the Prestarium analogue will be more effective in the case of coronary heart disease accompanied by stable angina. The medication prevents vascular disorders (stroke, myocardial infarction), prevents and alleviates attacks of chest pain in the heart with irradiation to the left arm and under the shoulder blade.

Prestans or Dalneva

Manufacturer: KRKA-RUS (Russia)
Release form: tablets

Active ingredient: amlodipine, perindopril

Pressure tablets Prestance and the analogue Dalneva have equivalent active substances, mechanism of action and are used to treat hypertension. The difference between the drugs is in the dosage of the drug, which in Prestance is 10 mg + 5 mg. Its use is more justified in therapeutic practice, since the drug has other dosages that make it possible to most effectively adjust the treatment of hypertension.

Brief description of Prestance

Medicines containing 2 basic active ingredients have different concentrates. The drug is released in tablet form. Small, whitish tablets containing perindopril and amlodipine, engraved as 5:5, 5:10, 10:5, 10:10. The drug contains:

1. Lactose monohydrate.
2. Cellulose microcrystals.
3. Food additive E551.
4. Stearine acid.

The tablet form is produced and packaged in a plastic bottle with a polypropylene dispenser. The box, made of cardboard, contains an annotation and 30 tablets of the drug. Packaging with control of the starting printout.

On a note! If an allergy is observed after use, then you must choose a substitute. The main Russian substitute is the tablet form of the drug Dalneva.

Prestance - a medicine for blood pressure, like any medicine, has instructions for use, studying it will not be superfluous. It is important to follow the instructions to prevent complications from developing. The tablets are taken orally with a large volume of water. It is correct to do this in the morning before meals.

The instructions for the drug give recommendations for use for heart pathologies. It is prescribed to an adult by a doctor, based on the course of the disease. A specialist can recommend medications that separately include amlodipine and perindopril, and then prescribe the drug Prestance, or an analogue containing the required amount of each component.

Elderly hypertensive patients with pathological kidney function are usually prescribed a small dosage, since the elimination of the drug takes a long time and is difficult. When using the medicine, the doctor monitors the amount of potassium and creatinine clearance. When the rate of blood flow through the paired organ is 60 ml per minute, the medication is not prescribed. At the same time, it is not prohibited to take medications with amlodipine separately; they are well absorbed in elderly patients.

For people with liver problems, carefully choose the dosage of the medicine for a single dose. When minor liver failure is diagnosed, the dose must be selected individually when consuming the drug. Although this blood pressure medication is effective, there are contraindications for use:

1. Reduced blood pressure.
2. State of shock.
3. There is a risk of swelling and malaise from the medication for allergy sufferers.
4. Kidney failure.
5. Lack of lactose, as it is found in auxiliary components.
6. Myocardial infarction.
7. The period of bearing a child.

This medicine should not be used by people under 18 years of age, since there is no information about the effect of the drug on a child.

Prestans or Noliprel

Manufacturer: LES LABORATORY SERVIER INDUSTRY (France)
Release form: tablets

Active ingredient: perindopril, indapamide

Both combined drugs have a hypotensive effect and actively reduce blood pressure, each influencing the body through its own mechanism of action. Prestanza analogue 10 mg + 10 mg Noliprel for hypertension accompanied by high blood pressure may be more effective. This is explained by the fact that one of the active substances in the structure of the drug is a diuretic, which relieves swelling and removes excess fluid from the body.

Prestans or Lorista

Manufacturer: KRKA (Slovenia)
Release form: tablets

Active ingredient: losartan

Lorista is a new generation medication that has a hypotensive effect. The medication has a beneficial effect on the myocardium in chronic heart failure and left ventricular hypertrophy, reducing premature mortality and vascular complications. In clinical practice, to improve the therapeutic outcome, the antihypertensive drug Lorista N is used, the effect of which is enhanced by the diuretic hydrochlorothiazide and prescribed in the presence of hypertension accompanied by edema.

Prestance® H

Hypersensitivity/angioedema

When taking ACE inhibitors. including perindopril, in rare cases, the development of angioedema of the face, extremities, lips, mucous membranes, tongue, glottis and/or larynx may occur (see section “Side effects”). This can happen at any time during therapy. If symptoms appear, the drug should be discontinued immediately and the patient should be observed until symptoms disappear completely. 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, vocal folds or larynx can lead to airway obstruction, in which case intensive care should be given immediately.

If such symptoms occur, epinephrine should be administered immediately and/or the airway should be secured. The patient should be under medical supervision until symptoms disappear completely and permanently.

In patients with a history of angioedema not associated with taking ACE inhibitors. the risk of its development may be increased when taking Prestance® N (see section “Contraindications”).

In rare cases, angioedema of the intestine has developed during therapy with ACE inhibitors. In this case, patients experienced abdominal pain as an isolated symptom or in combination with nausea or vomiting, in some cases, without previous angioedema of the face and with normal levels of C1-esterase. The diagnosis was made using abdominal computed tomography, ultrasound, or at the time of surgery. Symptoms disappeared after stopping the ACE inhibitors. Therefore, in patients with abdominal pain receiving ACE inhibitors, when carrying out differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine (see section “Side effects”).

Anaphylactoid reactions during desensitization

There are isolated reports of the development of anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy (for example, hymenoptera venom). In these same patients, anaphylactoid reactions could be avoided by temporarily discontinuing ACE inhibitors, and with accidental or careless resumption of treatment, reactions could develop again.

Neutropenia/agranulocytosis/thrombocytopenia/anemia

While taking ACE inhibitors, neutropenia/agranulocytosis, thrombocytopenia and anemia may occur. In patients with normal renal function and in the absence of other aggravating factors, neutropenia rarely develops.

Prestance® N should be used with extreme caution in patients with systemic connective tissue diseases, while taking immunosuppressants, allopurinol or procainamide, or a combination of these risk factors, especially in patients with impaired renal function.

Some patients developed severe infections, in some cases resistant to intensive antibiotic treatment. When Prestance® N is prescribed to such patients, it is recommended to periodically monitor leukocytes in the blood. Patients should report any signs of infectious diseases (eg, sore throat, fever) to their doctor.

Dual blockade of the renin-angiotensin-aldosterone system (RAAS)

There is evidence that concomitant use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalemia and renal impairment (including acute renal failure). Thus, double blockade of the RAAS by combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is not recommended (see sections “Interaction with other drugs” and “Pharmacodynamics”).

If dual blockade therapy is considered absolutely necessary, it should only be carried out under strict medical supervision and with regular monitoring of renal function, blood electrolyte concentrations and blood pressure.

ACE inhibitors should not be used in combination with angiotensin II receptor blockers in patients with diabetic nephropathy.

Primary aldosteronism

Patients with primary hyperaldosteronism are usually not susceptible to antihypertensive drugs that act by inhibiting the renin-angiotensin system.

Therefore, the use of this drug in such patients is not recommended.

Pregnancy

Prestance® N is contraindicated during pregnancy.

Those planning pregnancy should be prescribed an alternative antihypertensive agent with an established safety profile for use during pregnancy. If pregnancy is detected, treatment with ACE inhibitors should be stopped immediately and, if necessary, alternative antihypertensive therapy should be prescribed (see sections “Contraindications” and “Use during pregnancy and breastfeeding”).

Kidney failure

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

In patients with moderate renal failure (creatinine clearance 30-60 ml/min), the recommended initial dose is 2.5 mg + 3.5 mg every other day (see section “Dosage and Administration”). In such patients, it is necessary to regularly monitor the concentration of creatinine and potassium in the blood plasma.

In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney during therapy with ACE inhibitors, an increase in the concentration of urea and creatinine in the blood serum is possible, which usually resolves when therapy is discontinued. This effect is most often observed in patients with renal failure.

The additional presence of renovascular hypertension causes an increased risk of severe hypotension and renal failure in such patients.

In some patients with arterial hypertension without signs of renal vascular damage, an increase in the concentration of urea and creatinine in the blood serum is possible, especially when perindopril is co-administered with a diuretic, usually slight and transient. This effect is more often observed in patients with pre-existing renal impairment.

Patients with renal failure can take amlodipine in standard doses. Changes in plasma concentrations of amlodipine do not correlate with the degree of renal failure.

Amlodipine is not excreted from the body by dialysis.

Kidney transplant

Since there are no data on the use of Prestance® N in patients after kidney transplantation, it is not recommended to prescribe Prestance® N to these patients.

Renovascular hypotension

In patients with bilateral renal artery stenosis or arterial stenosis of a single functioning kidney during therapy with ACE inhibitors, the risk of developing arterial hypotension and renal failure increases (see section “Contraindications”). Taking diuretics may be an additional risk factor. Deterioration of renal function can be observed with even a slight change in serum creatinine concentration, even in patients with unilateral renal artery stenosis.

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 Prestance® N and place the patient under medical supervision (see section “Side Effects”).

In patients with impaired liver function, T1/2 and AUC of amlodipine are increased.

Elderly patients

In elderly patients, initiating therapy and increasing the dose should be done with caution. Before increasing the dose, it is necessary to assess the functional activity of the kidneys. Therefore, in these groups of patients it is necessary to regularly monitor the concentration of creatinine and potassium in the blood plasma.

Hypertensive crisis

The effectiveness and safety of amlodipine in hypertensive crisis has not been established.

Heart failure

Patients with heart failure should be treated with caution. Prestance® N should be used with caution in patients with chronic heart failure, since amlodipine may increase the risk of cardiovascular events and mortality.

Arterial hypotension

ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic hypotension rarely develops in patients without concomitant diseases. The risk of excessive reduction in blood pressure is increased in patients with reduced circulating blood volume, which can be observed during diuretic therapy, while following a strict salt-free diet, hemodialysis, diarrhea and vomiting, as well as in patients with severe arterial hypertension with high renin activity (see section "Interaction with other drugs").

In patients at increased risk of developing symptomatic hypotension, blood pressure, renal function and serum potassium levels should be carefully monitored during therapy with Prestance N.

A similar approach is used in patients with coronary artery disease and cerebrovascular diseases, in whom severe arterial hypotension can lead to myocardial infarction or cerebrovascular accident.

If arterial hypotension develops, the patient should be transferred to the supine position with legs elevated. If necessary, the volume of circulating blood should be replenished with intravenous administration of 0.9% sodium chloride solution. Transient arterial hypotension is not an obstacle to further taking the drug. After restoration of circulating blood volume and blood pressure, treatment can be continued.

Mitral stenosis/aortic stenosis/hypertrophic cardiomyopathy

ACE inhibitors should be prescribed with caution to patients with mitral stenosis, as well as to patients with left ventricular outflow tract obstruction (aortic stenosis, hypertrophic cardiomyopathy).

Ethnic differences

In patients of the Negroid race, angioedema develops more often than in representatives of other races while taking ACE inhibitors.

ACE inhibitors may have a less pronounced antihypertensive effect in patients of the Black race compared to representatives of other races. Perhaps this difference is due to the fact. that patients with arterial hypertension of the Negroid race often have low renin activity.

Cough

During therapy with Prestance® N, a dry cough may occur. The cough is unproductive, persists for a long time while taking drugs of this group and disappears after their discontinuation. This should be taken into account when carrying out the differential diagnosis of cough.

Surgery/general anesthesia

The use of ACE inhibitors in patients undergoing major surgery and/or general anesthesia can lead to a significant decrease in blood pressure if general anesthesia agents with a hypotensive effect are used. This is due to perindopril blocking the formation of angiotensin II against the background of a compensatory increase in renin activity. Therapy with Prestance® N should be discontinued one day before surgery.

If the development of arterial hypotension is associated with the described mechanism, blood pressure should be maintained by increasing the volume of circulating blood.

Hyperkalemia

Hyperkalemia may develop during treatment with ACE inhibitors, including perindopril. Risk factors for hyperkalemia are renal failure, age over 70 years, diabetes mellitus, some concomitant conditions (dehydration, acute decompensation of chronic heart failure, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone and its derivative eplerenone, triamterene, amiloride, or their combination), as well as potassium preparations or potassium-containing salt substitutes, as well as the use of other drugs that help increase the content of potassium in the blood plasma (for example, heparin, ACE inhibitors, angiotensin II antagonists, acetylsalicylic acid (3 g/day or more), inhibitors cyclooxygenase-2 (COX-2) and non-selective NSAIDs, immunosuppressants such as cyclosporine or tacrolimus, trimethoprim).

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 simultaneous use of Prestance® N and 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 (see section “Interaction with other drugs”).

Patients with diabetes mellitus

When prescribing the drug to patients with diabetes mellitus receiving hypoglycemic agents for oral administration or insulin, during the first month of therapy it is necessary to carefully monitor the concentration of glucose in the blood (see section “Interaction with other drugs”).

Potassium-sparing diuretics, potassium supplements, potassium-containing table salt substitutes and food supplements

The simultaneous administration of Prestance® N and potassium-sparing diuretics, as well as potassium preparations, potassium-containing table salt substitutes and food additives is not recommended (see section “Interaction with other drugs”).

Excipients

Due to the presence of lactose in the drug, the drug should not be prescribed to patients with hereditary lactose intolerance, lactase deficiency and glucose-galactose malabsorption.

Prestans or Lozap

Manufacturer: ZENTIVA A.S.
(Slovak Republic) Release form: tablets

Active ingredient: losartan

Both medications effectively normalize blood pressure in hypertension, acting through various biochemical processes on the body. An analogue of Prestance with the least side effects, Lozap, will be a higher priority in patients with diabetes mellitus complicated by the presence of protein in the urine. Drug therapy not only reduces blood pressure, but also inhibits the further development of chronic renal failure.

Instructions for use PRESTANCE

All instructions related to each of the components separately, as listed below, apply to the fixed Prestance combination.

Perindopril

Hypersensitivity/angioedema

There have been rare reports of angioedema of the face, extremities, lips, mucous membranes, tongue, glottis and/or larynx in patients treated with ACE inhibitors, including perindopril. These reactions may occur at any time during therapy. In such cases, Prestance should be stopped immediately and the necessary monitoring should be carried out until the symptoms disappear completely. If the swelling affects only the face and lips, it usually goes away on its own, although antihistamines can be used to treat symptoms.

Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, vocal cords, or larynx can lead to airway obstruction. If such symptoms occur, epinephrine (adrenaline) should be immediately administered subcutaneously and/or the airway should be secured. The patient should be under medical supervision until symptoms disappear completely and completely.

An increased risk of developing angioedema when taking an ACE inhibitor exists in patients who have had angioedema not associated with taking an ACE inhibitor.

In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. In this case, patients experience abdominal pain (with or without nausea and vomiting), in some cases, without previous angioedema of the face and with normal C1-esterase levels. The diagnosis is made using computed tomography of the abdominal region, ultrasound, or at the time of surgery. Symptoms disappear after stopping ACE inhibitors. Therefore, in patients with abdominal pain receiving ACE inhibitors, when carrying out differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine.

Anaphylactoid reactions during LDL apheresis

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

Anaphylactoid reactions during desensitization

Some patients receiving ACE inhibitors during desensitization therapy (eg, hymenoptera venom) have developed anaphylactoid reactions. In a number of cases, these reactions were avoided by temporarily withdrawing the ACE inhibitor, and if the drug was accidentally taken, the anaphylactoid reaction occurred again.

Neutropenia, agranulocytosis, thrombocytopenia, anemia

Neutropenia/agranulocytosis, thrombocytopenia and anemia were observed while taking ACE inhibitors. In patients with normal liver function and in the absence of other complicating factors, neutropenia rarely develops. Perindopril should be used with extreme caution in patients with diffuse connective tissue diseases, while taking immunosuppressants, allopurinol or procainamide, especially in patients with pre-existing liver dysfunction. Some of these 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.

Double blockade of the RAAS

There is evidence that the combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of hypotension, hyperkalemia and renal impairment (including acute renal failure) compared with monotherapy. In this regard, double blockade of the RAAS by combined administration of an ACE inhibitor and an angiotensin II receptor antagonist or aliskiren is not recommended, especially in patients with diabetic nephropathy.

In some cases, when the combined use of ACE inhibitors and angiotensin II receptor antagonists is absolutely indicated, careful supervision by a specialist and mandatory monitoring of renal function, water-electrolyte balance and blood pressure are necessary. This applies to the use of candesartan or valsartan as adjunctive therapy to ACE inhibitors in patients with chronic heart failure. Carrying out double blockade of the RAAS under the careful supervision of a specialist and mandatory monitoring of renal function, water-electrolyte balance and blood pressure is possible in patients with chronic heart failure with intolerance to aldosterone antagonists (spironolactone), who have persistence of symptoms of chronic heart failure, despite other adequate therapy .

Arterial hypotension

ACE inhibitors can cause a sharp decrease in blood pressure. Arterial hypotension with clinical manifestations rarely develops in patients without concomitant diseases. The risk of an excessive decrease in blood pressure is increased in patients with reduced blood volume, which can be observed during diuretic therapy, following a strict salt-free diet, hemodialysis, diarrhea and vomiting, as well as in patients with severe arterial hypertension with high renin activity. In patients at increased risk of developing symptomatic hypotension, blood pressure, renal function and serum potassium levels should be carefully monitored during therapy with Prestance.

The same precautions apply to patients with coronary artery disease or cerebrovascular disease with an excessive fall in blood pressure due to myocardial infarction or a cerebrovascular event.

If arterial hypotension develops, the patient should be placed in a supine position with legs elevated. If necessary, the bcc should be replenished with the intravenous administration of 0.9% sodium chloride solution. Transient arterial hypotension is not an obstacle to further taking the drug. After restoration of blood volume and blood pressure, treatment can be continued.

Mitral stenosis, aortic stenosis, hypertrophic cardiomyopathy

Prestance, like other ACE inhibitors, should be prescribed with extreme caution to patients with mitral stenosis, left ventricular outflow tract obstruction (aortic stenosis, hypertrophic cardiomyopathy).

Kidney failure

In patients with renal failure (creatinine clearance <60 ml/min), individual selection of doses of perindopril and amlodipine is recommended. Such patients require regular monitoring of potassium and creatinine levels in the blood serum.

In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney during therapy with ACE inhibitors, cases of increased urea and creatinine in the blood serum were observed, usually reversible when therapy was discontinued. This is most likely to occur in patients with renal failure. Renovascular hypertension also has an increased risk of severe hypotension and renal failure. In some patients with arterial hypertension without signs of renal vascular damage, there may be an increase in the concentration of urea and creatinine in the blood serum (especially with a combination of perindopril and a diuretic), usually slight and transient. This is most likely in patients with pre-existing kidney failure.

Liver failure

In rare cases, taking ACE inhibitors has been accompanied by the development of a syndrome that begins with cholestatic jaundice and progresses to fulminant liver necrosis, sometimes with death. The mechanism of development of this syndrome is unclear. If jaundice or a significant increase in liver enzyme activity occurs while taking ACE inhibitors, patients should stop taking the drug and consult a doctor for a thorough medical examination.

Ethnic differences

In patients of the Negroid race, angioedema develops more often than in representatives of other races while taking ACE inhibitors.

Perindopril, like other ACE inhibitors, may have a less pronounced hypotensive effect in patients of the Black race compared to representatives of other races. Perhaps this difference is due to the fact that arterial hypertension in patients of the Negroid race very often occurs against the background of low renin activity.

Cough

Cases of cough have been reported during ACE inhibitor therapy. The cough is non-productive, incessant and goes away when therapy is stopped. Cough caused by ACE inhibitor use should be considered as part of the differential diagnosis of cough.

Surgery/general anesthesia

During surgery or during anesthesia with drugs that cause arterial hypotension, Prestance can block the formation of angiotensin II, as a consequence of compensatory release of renin. It is recommended to stop treatment the day before surgery. When hypotension occurs, which is presumably associated with this mechanism of action, the volume of blood volume should be increased.

Hyperkalemia

During treatment with ACE inhibitors, incl. and perindopril, cases of hyperkalemia have been reported. Risk factors for hyperkalemia are renal failure, impaired renal function, old age (over 70 years), diabetes mellitus, some concomitant conditions (dehydration, acute decompensation in heart failure, metabolic acidosis), concomitant use of potassium-sparing diuretics (spironolactone, eplerenone, triamterene, amiloride ), as well as potassium preparations or potassium-containing substitutes for table salt, as well as the use of other drugs that help increase the content 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 lead to serious, sometimes fatal arrhythmias. If simultaneous use of perindopril and 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.

Patients with diabetes mellitus

Patients with diabetes mellitus receiving oral hypoglycemic agents or insulin should carefully monitor blood glucose concentrations during the first month of ACE inhibitor therapy.

Amlodipine

The safety and effectiveness of amlodipine in hypertensive crisis has not been established.

In elderly patients, the dose of the drug should be increased with caution.

Liver failure

T1/2 and AUC values ​​are higher in patients with impaired liver function. Recommended doses for this category of patients have not been established, so treatment should begin with the minimum effective dose and increase it with caution. Patients with severe hepatic impairment require slow dose titration and close monitoring.

Kidney failure

In patients with renal failure, amlodipine can be used in normal doses. Changes in plasma amlodipine concentrations do not correlate with the degree of renal failure. Amlodipine is not eliminated by dialysis.

Heart failure

Caution is required when prescribing amlodipine to patients with heart failure.

In a long-term placebo-controlled study in patients with severe heart failure (NYHA classes III and IV), the incidence of pulmonary edema was higher in the amlodipine-treated group than in the placebo group. Calcium channel blockers, including amlodipine, should be used with caution in patients with congestive heart failure. they may have an increased risk of cardiovascular complications and mortality in the future.

Prestance

The combination of Prestance with lithium, potassium-sparing diuretics, potassium supplements or dantrolene is not recommended.

Due to the presence of lactose in the drug, the drug should not be prescribed to patients with hereditary lactose intolerance, glucose/galactose malabsorption syndrome, or lapp lactase deficiency.

Impact on the ability to drive vehicles and machinery

There have been no studies of the effect of the drug Prestance on the ability to drive vehicles and operate machinery. Amlodipine may have a slight or moderate effect on the ability to drive vehicles and operate machinery. If the patient suffers from dizziness, headache, tiredness, fatigue or nausea, the response may be impaired. Patients should exercise caution during these types of activities, especially at the beginning of therapy.

Preclinical safety data

Perindopril

In chronic oral toxicity studies (in rats and monkeys), the receptor organ is the kidney, and the damage is reversible.

No mutagenicity was observed in in vitro or in vivo studies.

Reproductive toxicity studies (in rats, mice, rabbits and monkeys) showed no evidence of embryotoxicity or teratogenicity. However, ACE inhibitors as a class have been shown to have adverse effects on late fetal development, leading to fetal death and congenital defects in rodents and rabbits:

• kidney damage and an increase in perinatal and postnatal mortality were observed.

No carcinogenicity was observed in studies with long-term administration in rats and mice.

Amlodipine

Reproductive toxicity studies in rats and mice have shown delayed delivery, increased duration of labor, and decreased offspring survival at doses approximately 50 times the maximum mg/kg recommended for humans.

There was no effect on fertility in rats treated with amlodipine (for males for 64 days and females for 14 days before mating) at doses up to 10 mg/kg/day (eight* times the recommended human dose, based on 10 mg/m2) . Other studies in which male rats were administered amlodipine besylate for 30 days at mg/kg doses comparable to human doses found a decrease in plasma FSH and testosterone, as well as a decrease in sperm density and the number of maternal spermatids and Sertolli cells.

In rats and mice that were administered amlodipine for 2 years at doses of 0.5, 1.25 and 2.5 mg/kg/day, no signs of carcinogenicity were detected. The highest doses (for mice, the same as for rats, exceeding the maximum recommended by 2 times, at the rate of 10 mg/kg/day) were close to the maximum tolerated doses for mice, but not for rats. Mutagenicity studies did not reveal drug-related effects at the gene or chromosomal level.

*calculated for patient body weight 50 kg

Vamloset

Manufacturer: KRKA-RUS (Russia)
Release form: tablets

Active ingredient: amlodipine, valsartan

The Vamloset analogue is a combined agent that can lower blood pressure by relaxing the smooth muscle fibers of the vascular wall, which leads to a decrease in peripheral vascular resistance and blood pressure indicators. The medication does not affect the pulse wave frequency. Therapy with the Russian analogue rarely provokes the development of a dry cough as a side effect in the treatment of hypertension.