Perineva Tablets, box, 90 pcs., 4 mg, for oral administration

Compound

Pharmacodynamics

Co-Perineva® is a combination drug containing an ACE inhibitor - perindopril and a thiazide-like diuretic - indapamide. The drug has antihypertensive, diuretic and vasodilating effects.

Co-Perineva® has a pronounced dose-dependent antihypertensive effect, independent of the patient’s age and body position and not accompanied by reflex tachycardia. Does not affect lipid metabolism (total cholesterol, LDL, VLDL, HDL, triglycerides (TG) and carbohydrates), incl. in patients with diabetes mellitus. Reduces the risk of hypokalemia caused by diuretic monotherapy.

The antihypertensive effect lasts for 24 hours.

A stable reduction in blood pressure is achieved within 1 month with the use of the drug Co-Perineva® without an increase in heart rate. Stopping treatment does not lead to the development of withdrawal syndrome.

Perindopril is an ACE inhibitor, the mechanism of action of which is associated with inhibition of ACE activity, leading to a decrease in the formation of angiotensin II, eliminates the vasoconstrictor effect of angiotensin II, reduces the secretion of aldosterone. The use of perindopril does not lead to sodium and fluid retention and does not cause reflex tachycardia during long-term treatment. The antihypertensive effect of perindopril develops in patients with low or normal plasma renin activity.

Perindopril acts through its main active metabolite, perindoprilate. Its other metabolites are inactive. The effect of the drug Co-Perineva® leads to:

- dilation of veins (reduction of preload on the heart), caused by changes in PG metabolism;

- reduction of peripheral vascular resistance (reduction of afterload on the heart).

In patients with heart failure, perindopril helps:

- decreased filling pressure of the left and right ventricles;

- increase in cardiac output and cardiac index;

- increasing regional blood flow in the muscles.

Perindopril is effective for arterial hypertension of any severity: mild, moderate and severe. The maximum antihypertensive effect develops 4–6 hours after a single oral dose and persists throughout the day. Discontinuation of therapy does not lead to the development of withdrawal syndrome.

It has vasodilating properties and restores the elasticity of large arteries. The addition of a thiazide-like diuretic enhances (addition) the antihypertensive effect of perindopril.

Indapamide is a sulfonamide derivative and is a diuretic. Inhibits the reabsorption of sodium in the cortical segment of the renal tubules, increasing the excretion of sodium and chlorine by the kidneys, thus leading to increased diuresis. To a lesser extent increases the excretion of potassium and magnesium. Having the ability to selectively block “slow” calcium channels, indapamide increases the elasticity of arterial walls and reduces peripheral vascular resistance. It has a hypotensive effect in doses that do not have a pronounced diuretic effect. Increasing the dose of indapamide does not increase the antihypertensive effect, but increases the risk of adverse events.

Indapamide in patients with arterial hypertension has no effect on lipid metabolism: TG, LDL and HDL and carbohydrate metabolism, even in patients with diabetes mellitus and arterial hypertension.

Perineva and Perindopril - the difference between medications

Perineva and Perindopril are ACE inhibitor drugs used to treat diseases accompanied by arterial hypertension. The main active component in the composition of drugs is perindopril, which, when entering the human body, is converted into the active metabolite perindoprilat.

The medications have an identical composition and cumulative effect, effectively stabilize blood pressure, and improve a person’s overall well-being.

Both medications are prescribed to reduce the likelihood of developing severe complications after a stroke, micro-stroke, myocardial infarction or coronary heart disease.

Perindopril is considered a cheaper analogue of Periniva, the cost of which is several times higher.

But this drug is much more likely to cause unwanted side effects. Perineva is most often well tolerated by the body and does not cause negative reactions.

Pharmacokinetics

The combined use of perindopril and indapamide does not change their pharmacokinetic parameters compared to the separate administration of these drugs.

Perindopril after oral administration is rapidly absorbed from the gastrointestinal tract. Bioavailability is 65–70%. Eating reduces the conversion of perindopril to perindoprilat. T1/2 of perindopril from blood plasma is 1 hour.

Cmax in blood plasma is achieved 3–4 hours after oral administration. Since taking with food reduces the conversion of perindopril to perindoprilat and the bioavailability of the drug, perindopril should be taken once a day in the morning, before breakfast. Taking perindopril once a day, equilibrium concentration is achieved within 4 days.

It is metabolized in the liver to form an active metabolite - perindoprilate. In addition to the active metabolite perindoprilate, perindopril forms 5 more inactive metabolites. The binding of perindoprilate to plasma proteins is dose-dependent and amounts to 20%. Perindoprilat easily passes through histohematic barriers, excluding the blood-brain barrier; a small amount penetrates the placenta and into breast milk. Excreted by the kidneys, T1/2 of perindoprilate is about 17 hours. It does not accumulate.

In elderly patients and in patients with renal and heart failure, the elimination of perindoprilate is slowed down.

In case of renal failure, it is recommended to reduce the dose of perindopril depending on the severity of renal failure (creatinine clearance). The dialysis Cl of perindoprilate is 70 ml/min.

The kinetics of perindopril is altered in patients with liver cirrhosis: hepatic clearance is reduced by half. However, the amount of perindoprilate formed does not decrease, which does not require dose adjustment.

Indapamide. Quickly and almost completely absorbed into the gastrointestinal tract. Eating slightly slows down absorption, but does not significantly affect the amount of indapamide absorbed. Cmax in blood plasma is achieved 1 hour after oral administration of a single dose. Binds to plasma proteins by 79%. T1/2 ranges from 14 to 24 hours (average 18 hours). Does not accumulate.

Metabolized in the liver. It is excreted by the kidneys (70%) mainly in the form of metabolites (the fraction of the unchanged drug is about 5%) and by the intestines with bile in the form of inactive metabolites (22%). In patients with renal failure, the pharmacokinetic parameters of indapamide do not change significantly.

Popular analogues

If the drug cannot be used for any reason - due to contraindications or side effects, a decision is made to replace it with an analogue.

Analog drugs can be cheaper or more expensive, and can be determined not only by manufacturer, but also by composition, main active ingredient and mechanism of action. Therefore, replacing a drug against arterial hypertension should be selected only by a doctor.

Amlodipine

Amlodipine is a drug prescribed for various diseases associated with high blood pressure. Unlike Perindopril, which is an ATP inhibitor, Amlodipine is a slow calcium channel blocker and has a different mechanism of therapeutic action.

The pharmacological action of Amlodipine is aimed at completely blocking the entry of calcium ions into smooth muscles and myocardial tissue. This reduces blood pressure and reduces the load on the heart muscle.

Amlodipine is approved for use in renal and liver failure. But in this case, treatment is carried out under strict medical supervision, with mandatory adjustment of the dose of the medication. Main contraindications to the use of Amlodipine:

• severe form of arterial hypotension;
• children and adolescents up to 18 years of age;
• unstable heart failure after myocardial infarction.

Taking a pharmacological drug may be accompanied by side effects - tachycardia, shortness of breath, nausea, painful abdominal cramps, skin redness, rashes and swelling.

Lisinopril

Lisinopril is an analogue of Perineva, classified as an ATP inhibitor and used to normalize high blood pressure. The drug contains the active substance lisinopril.

This component suppresses the synthesis of ACE, promoting the expansion of the vascular bed, normalizes blood circulation and reduces the load on the myocardium, increases the tone and elasticity of the walls of blood vessels.

The pharmacological drug is available in the form of tablets, which must be taken one every day. Lisinopril is approved for use in patients suffering from diabetes mellitus accompanied by obesity. The pharmacological agent has a wide list of contraindications for use:

• all trimesters of pregnancy and breastfeeding;
• children and adolescents up to 18 years of age;

• hereditary predisposition to Quincke's edema;
• liver and kidney pathologies;
• individual intolerance to the components that make up Lisinopril.

Lisinopril can cause a number of side effects such as dry cough, stool upset, nausea, digestive disorders, headaches and dizziness.

Noliprel

Noliprel is a combined-action antihypertensive drug that contains the active components perindopril and indapamide. The first substance is a powerful inhibitor of angiotensin-converting enzyme (ATP), the second is a diuretic. This combination of active ingredients provides a quick and effective lowering of blood pressure.

The tablets are taken for a long time, even after normalization of blood pressure levels; Noliprel is often prescribed to the patient for life. The peculiarity of the drug is that it has a cumulative effect and is not used as an emergency medicine for hypertensive patients.

Noliprel is highly effective in any form and stage of arterial hypertension, even advanced ones.

The main difference between Perindopril and Noliprel is the composition.

If the first medicine contains only one active component with the same name, then the second one is a combination medicine and contains two active ingredients, which increases its effectiveness. The cost of the drug is significantly higher than Perineva.

Perindopril and Prestarium

Prestarium is a combination drug belonging to the group of ATP inhibitors. The pharmacological effect of the drug is determined by the main active substance of perindopril, arginine.

Main indications for Prestarium:

• arterial hypertension;
• heart failure.

The medicine is used for various diseases of the cardiovascular system, accompanied by a sharp increase in blood pressure and painful spasms in the chest. Prestarium normalizes the functioning of the myocardium and blood vessels, as well as left ventricular hypertrophy, and increases tolerance to various loads.

Perindopril or Prestarium, which is better - when choosing a drug, you need to take into account that the former causes side effects much more often than Prestarium. Tablets can cause attacks of nausea, abdominal pain, headaches, skin redness and rashes, liver problems, and dry mouth. Prestarium is most often well tolerated by the body, so it can be taken for quite a long time. In some cases, the drug is prescribed to the patient for life.

Prestarium is prescribed not only for therapeutic purposes, but also for preventive purposes - to prevent the development of ischemic attacks and strokes.

Enalapril and Perindopril

Enalapril is one of the most accessible and widespread analogues of Perindopril, which is produced by many domestic and foreign manufacturers. The drug also belongs to ACE inhibitors, the action of which is aimed at normalizing blood pressure.

The main active substance in its composition is enalapril maleate, the effect of which is similar to perindopril.

When choosing a drug, you need to take into account that both medications are cumulative, but the stabilizing effect of Enalapril persists for 12 hours after taking the tablet. The results of Perindopril last for 24 hours. Both medications are approved for use in diabetes mellitus.

The difference between these medications is their cost. The price of Enalapril, depending on the manufacturer, is 10-15 times lower than Perineva, despite the identical pharmacological effects of the drugs.

Enalapril can cause a number of side effects - headaches and dizziness, attacks of dry cough, skin rashes accompanied by itching and burning, drowsiness, increased fatigue, and anxiety.

Contraindications

hypersensitivity to the active substance, any ACE inhibitor, sulfonamide derivatives or any excipients of the drug;

angioedema (hereditary, idiopathic or angioedema) while taking other ACE inhibitors (history);

severe renal failure (creatinine Cl less than 30 ml/min);

bilateral renal artery stenosis, stenosis of the artery of a single kidney;

refractory hyperkalemia;

lactose intolerance, lactase deficiency or glucose-galactose malabsorption;

simultaneous use of drugs that prolong the QT interval on the ECG, simultaneous use with antiarrhythmic drugs that can cause ventricular tachycardia of the “pirouette” type (see “Interaction”);

severe liver failure (including encephalopathy);

pregnancy, breastfeeding, age under 18 years (efficacy and safety have not been established);

Given the lack of sufficient experience with use, Co-Perineva® should not be taken by patients on dialysis and patients with untreated decompensated heart failure.

With caution: systemic connective tissue diseases (including systemic lupus erythematosus (SLE), scleroderma), therapy with immunosuppressants (risk of developing neutropenia, agranulocytosis), inhibition of bone marrow hematopoiesis, decreased blood volume (taking diuretics, salt-free diet, vomiting, diarrhea) , angina pectoris, cerebrovascular diseases, renovascular hypertension, diabetes mellitus, chronic heart failure (functional class IV according to the NYHA classification), hyperuricemia (especially accompanied by gout and urate nephrolithiasis), blood pressure lability, elderly patients, hemodialysis using high-flow polyacrylonitrile membranes; before the LDL apheresis procedure, simultaneous desensitizing therapy with allergens (for example, hymenoptera venom); condition after kidney transplantation, stenosis of the aortic and/or mitral valve, hypertrophic obstructive cardiomyopathy.

Features of the drug Perindopril

Perindopril is a medicine that is used for chronic heart failure, arterial hypertension, and to prevent recurrent strokes in patients who have suffered a stroke or mini-stroke. Belongs to the group of ACE inhibitors, prescribed to reduce the likelihood of developing cardiovascular complications.

The drug should not be used during pregnancy and breastfeeding, in childhood and adolescence, in the presence of a history of angioedema and in case of individual intolerance to the active components included in its composition.

The medication is used with extreme caution for aortic stenosis, pericarditis, severe autoimmune diseases, atherosclerosis, renal failure, leukopenia or thrombocytopenia.

When taking a medication, you need to consider its compatibility with alcohol. Alcohol increases blood pressure, and pharmaceutical drugs lower it. This combination can cause a serious deterioration in a person’s well-being and lead to the development of severe complications - hypertensive crisis, arrhythmia, cardiac conduction disorders.

Use during pregnancy and breastfeeding

Pregnancy. Taking Co-Perineva® is contraindicated during pregnancy. If you are planning pregnancy or if it occurs while taking Co-Perineva®, you should immediately stop taking the drug and prescribe other antihypertensive therapy. You should not use Co-Perineva® in the first trimester of pregnancy. There have been no controlled clinical studies on the use of ACE inhibitors in pregnant women. Limited data indicate that taking ACE inhibitors in the first trimester did not lead to fetotoxicity-related fetal malformations, but the fetotoxic effect of ACE inhibitors cannot be completely excluded. The drug Co-Perineva® is contraindicated in the second and third trimesters of pregnancy. Long-term use of ACE inhibitors in the second and third trimesters of pregnancy can lead to impaired fetal development (decreased renal function, oligohydramnios, delayed ossification of the skull bones) and the development of complications in the newborn (renal failure, arterial hypotension, hyperkalemia).

Long-term use of thiazide diuretics in the third trimester of pregnancy can cause hypovolemia in the mother and a decrease in uteroplacental blood flow, which leads to fetoplacental ischemia and fetal growth retardation. In rare cases, while taking diuretics, hypoglycemia and thrombocytopenia may develop in the fetus/newborn. If a woman took an ACE inhibitor in the second and third trimesters of pregnancy, it is recommended to conduct an ultrasound of the kidneys and skull of the fetus/newborn.

In newborns whose mothers received therapy with ACE inhibitors, hypotension may occur, so newborns should be under close medical supervision.

Breastfeeding period. The drug Co-Perineva® is contraindicated during breastfeeding.

It is not known whether perindopril is excreted in breast milk.

Indapamide is excreted in breast milk. Causes a decrease or suppression of lactation. The newborn may develop hypersensitivity to sulfonamide derivatives, hypokalemia and nuclear jaundice.

It is necessary to assess the significance of therapy for the mother and make a decision to stop breastfeeding or stop taking the drug.

Brief summary

Perineva and Perindopril are effective drugs from the category of ATP inhibitors. They are used to treat arterial hypertension and various diseases of the cardiovascular system, accompanied by a sharp increase in blood pressure.

Medicines can be used not only for treatment, but also for the prevention of complications after a heart attack or stroke. In case of existing contraindications or individual intolerance, pharmacological agents with a similar principle of action are selected.

Side effects

Perindopril has an inhibitory effect on the RAAS and reduces the excretion of potassium ions by the kidneys while taking indapamide. The risk of developing hypokalemia (serum potassium content less than 3.4 mmol/l) in patients using the drug Co-Perineva® at a daily dose of 0.625 mg/2 mg is 2%, 1.25 mg/4 mg - 4% and 2.5 mg/8 mg - 6%.

WHO classification of the incidence of side effects: very often - ≥1/10; often - from ≥1/100 to <1/10; uncommon - from ≥1/1000 to <1/100; rarely - from ≥1/10000 to <1/1000; very rare - from <1/10000, frequency unknown - cannot be estimated based on available data. Within each group, adverse effects are presented in order of decreasing severity.

From the hematopoietic organs: very rarely - thrombocytopenia, leukopenia/neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (there are reports with the use of ACE inhibitors). In certain clinical situations (conditions after kidney transplantation or in patients on hemodialysis or peritoneal dialysis), ACE inhibitors may cause anemia.

From the central and peripheral nervous system: often - paresthesia, headache, dizziness, vertigo; infrequently - mood lability, sleep disturbances; very rarely - confusion.

From the senses: often - visual impairment, tinnitus.

From the cardiovascular system: often - a pronounced decrease in blood pressure, incl. orthostatic hypotension; very rarely - arrhythmias, incl. and bradycardia, ventricular tachycardia, atrial fibrillation, as well as angina pectoris, myocardial infarction, possibly secondary, due to a decrease in blood pressure in high-risk patients; frequency unknown - ventricular tachycardia of the “pirouette” type (possibly fatal).

From the respiratory system: often - a dry cough that persists for a long time during the use of ACE inhibitors and disappears after their cessation; dyspnea; uncommon - bronchospasm; very rarely - eosinophilic pneumonia, rhinitis.

From the digestive system: often - constipation, dryness of the oral mucosa, loss of appetite, nausea, epigastric pain, abdominal pain, impaired taste perception, vomiting, dyspepsia, diarrhea; very rarely - pancreatitis, angioedema of the intestine, jaundice; frequency has not been established - in case of liver failure, there is a possibility of developing hepatic encephalopathy.

From the skin and subcutaneous fat: often - itching, skin rash, maculopapular rash; uncommon - angioedema of the face, extremities, lips, oral mucosa, tongue, vocal folds and/or larynx, urticaria; hypersensitivity reactions, mainly dermatological, in patients with a history of allergic reactions; worsening of SLE; very rarely - erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome; isolated cases of photosensitivity reaction.

From the musculoskeletal system: often - muscle spasms.

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

From the reproductive system: infrequently - impotence.

Other: often - asthenia; infrequently - increased sweating.

Laboratory indicators: rarely - hypercalcemia; frequency unknown - increase in QT on the ECG; increased concentrations of uric acid and glucose in the blood serum while taking the drug; increased activity of liver enzymes; a slight increase in plasma creatinine concentration, reversible after cessation of therapy, which often develops against the background of renal artery stenosis or stenosis of the artery of a single kidney, arterial hypertension during diuretic therapy, and renal failure; hypokalemia, especially significant for patients at risk; hypochloremia can lead to compensatory metabolic alkalosis (the likelihood and severity of the effect is low); hyperkalemia is often reversible; hyponatremia with hypovolemia, leading to a decrease in blood volume and orthostatic hypotension.

According to clinical studies, side effects correspond to the previously established safety profile of the combination of perindopril and indapamide. In rare cases, the following serious adverse events have developed: hyperkalemia, acute renal failure, arterial hypotension and cough, and the possible development of angioedema.

Perineva, 4 mg, tablets, 30 pcs.

Stable ischemic heart disease.

If an episode of unstable angina (major or minor) develops during the first month of therapy with Perineva®, it is necessary to assess the benefit/risk ratio of therapy with this drug.

Arterial hypotension.

ACE inhibitors can cause a sharp decrease in blood pressure. In patients with uncomplicated hypertension, symptomatic hypotension rarely occurs after the first dose. The risk of excessive reduction in blood pressure is increased in patients with reduced blood volume during diuretic therapy, while following a strict salt-free diet, hemodialysis, as well as with diarrhea or vomiting, or in those suffering from severe renin-dependent hypertension. Severe arterial hypotension was observed in patients with severe CHF, both in the presence of concomitant renal failure and in its absence. The most common arterial hypotension can develop in patients with more severe CHF, taking loop diuretics in high doses, as well as against the background of hyponatremia or renal failure. Close medical monitoring is recommended for these patients during initiation of therapy and during dosage titration. The same applies to patients with coronary artery disease or cerebrovascular diseases, in whom an excessive decrease in blood pressure can lead to myocardial infarction or cerebrovascular complications.

If arterial hypotension develops, it is necessary to place the patient in a horizontal position with elevated legs and, if necessary, administer an intravenous solution of sodium chloride to increase blood volume. Transient arterial hypotension is not a contraindication for further therapy. After restoration of blood volume and blood pressure, treatment can be continued subject to careful selection of the dose of the drug.

In some patients with CHF and normal or low blood pressure, an additional decrease in blood pressure may occur during therapy with Perineva®. This effect is expected and is usually not a reason to discontinue the drug. If arterial hypotension is accompanied by clinical manifestations, dose reduction or discontinuation of Perineva® may be required.

Aortic or mitral valve stenosis/hypertrophic cardiomyopathy.

ACE inhibitors, incl. and perindopril should be administered with caution to patients with mitral valve stenosis and left ventricular outflow tract obstruction (aortic valve stenosis and hypertrophic cardiomyopathy).

Renal dysfunction.

In patients with renal insufficiency (Cl creatinine <60 ml/min), the initial dose of Perineva® should be adjusted in accordance with Cl creatinine (see section "Dosage and Administration") and then depending on the therapeutic response. For such patients, regular monitoring of the concentration of potassium ions and creatinine in the blood serum is necessary.

In patients with symptomatic heart failure, arterial hypotension that develops during the initial period of therapy with ACE inhibitors can lead to deterioration of renal function. Cases of acute renal failure, usually reversible, have sometimes been reported in such patients.

In some patients with bilateral renal artery stenosis or renal artery stenosis of a solitary kidney (especially in the presence of renal failure), an increase in serum concentrations of urea and creatinine was observed during therapy with ACE inhibitors, which was reversible after discontinuation of therapy. In patients with renovascular hypertension during therapy with ACE inhibitors, there is an increased risk of developing severe arterial hypotension and renal failure. Treatment of such patients should begin under close medical supervision, with small doses of the drug and with further adequate dose selection. During the first weeks of therapy with Perineva®, it is necessary to discontinue diuretics and regularly monitor renal function. In some patients with arterial hypertension, in the presence of previously undiagnosed renal failure, especially with concomitant therapy with diuretics, there was a slight and temporary increase in serum urea and creatinine concentrations. In this case, it is recommended to reduce the dose of Perineva® and/or discontinue the diuretic.

Patients on hemodialysis.

Several cases of persistent, life-threatening anaphylactic reactions have been reported in patients undergoing dialysis using high-flux membranes and concomitantly taking ACE inhibitors. If hemodialysis is necessary, a different type of membrane must be used.

Kidney transplantation.

There is no experience with the use of perindopril in patients with recent kidney transplantation.

Hypersensitivity/angioedema.

Rarely in patients taking ACE inhibitors, incl. perindopril, angioedema of the face, extremities, lips, mucous membranes, tongue, glottis and/or larynx developed. This condition can develop at any time during treatment. If angioedema develops, treatment should be stopped immediately, and the patient should be under medical supervision until symptoms disappear completely. Angioedema of the lips and face usually does not require treatment; Antihistamines can be used to reduce the severity of symptoms. Angioedema of the tongue, glottis, or larynx can be fatal. If angioedema develops, it is necessary to immediately administer epinephrine (adrenaline) subcutaneously and ensure airway patency. ACE inhibitors are more likely to cause angioedema in black patients.

Patients with a history of angioedema not associated with the use of ACE inhibitors may be at high risk of developing angioedema while taking an ACE inhibitor.

Anaphylactoid reactions during the LDL apheresis procedure (LDL apheresis).

In patients prescribed ACE inhibitors during the procedure of LDL apheresis using dextran sulfate absorption, in rare cases, an anaphylactic reaction may develop. It is recommended to temporarily discontinue the ACE inhibitor before each apheresis procedure.

Anaphylactic reactions during desensitization.

In patients receiving ACE inhibitors during a course of desensitization (for example, hymenoptera venom), in very rare cases life-threatening anaphylactic reactions may develop. It is recommended to temporarily discontinue the ACE inhibitor before each desensitization procedure.

Liver failure.

During therapy with ACE inhibitors, it is sometimes possible to develop a syndrome that begins with cholestatic jaundice and then progresses to fulminant liver necrosis, sometimes with death. The mechanism of development of this syndrome is unclear. If jaundice or elevated liver enzymes occur while taking an ACE inhibitor, the ACE inhibitor should be discontinued immediately and the patient should be closely monitored. It is also necessary to conduct an appropriate examination.

Neutropenia/agranulocytosis/thrombocytopenia/anemia.

Cases of neutropenia/agranulocytosis, thrombocytopenia and anemia have been reported in patients treated with ACE inhibitors. With normal renal function in the absence of other complications, neutropenia rarely develops. The drug Perineva® should be used with great caution in patients with systemic connective tissue diseases (for example, SLE, scleroderma), simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, as well as when combining all of these factors, especially with existing renal impairment. Such patients may develop severe infections that do not respond to intensive antibiotic therapy. When carrying out therapy with Perineva® in patients with the above factors, it is recommended to periodically monitor the number of leukocytes in the blood and warn the patient about the need to inform the doctor about the appearance of any symptoms of infection.

In patients with congenital glucose-6-phosphate dehydrogenase deficiency

There have been isolated cases of hemolytic anemia.

Negroid race.

The risk of developing angioedema in black patients is higher. Like other ACE inhibitors, perindopril is less effective in lowering blood pressure in black patients, possibly due to the higher prevalence of low-renin conditions in this population of patients with arterial hypertension.

Cough.

During therapy with ACE inhibitors, a persistent, non-productive cough may develop, which stops after discontinuation of the drug. This should be taken into account in the differential diagnosis of cough.

Surgery/general anesthesia.

In patients whose condition requires major surgery or anesthesia with drugs that cause hypotension, ACE inhibitors, including perindopril, may block the formation of angiotensin II with compensatory renin release. One day before surgery, therapy with ACE inhibitors must be discontinued. If the ACE inhibitor cannot be canceled, then arterial hypotension developing according to the described mechanism can be corrected by increasing the volume of blood volume.

Hyperkalemia.

During therapy with ACE inhibitors, including perindopril, the concentration of potassium ions in the blood may increase in some patients. The risk of hyperkalemia is increased in patients with renal and/or heart failure, decompensated diabetes mellitus and patients using potassium-sparing diuretics, potassium supplements or other drugs that cause hyperkalemia (eg heparin). If it is necessary to prescribe these drugs simultaneously, it is recommended to regularly monitor the potassium content in the blood serum.

Diabetes.

In patients with diabetes mellitus taking oral hypoglycemic agents or insulin, blood glucose concentrations should be carefully monitored during the first few months of ACE inhibitor therapy.

Lithium.

Concomitant use of lithium and perindopril is not recommended.

Potassium-sparing diuretics, drugs containing potassium, potassium-containing foods and nutritional supplements.

Concomitant use with ACE inhibitors is not recommended.

Lactose.

Perineva® tablets contain lactose. Therefore, patients with hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption syndrome should not take this drug.

Impact on the ability to drive a car or perform work that requires increased speed of physical and mental reactions.

It is necessary to take into account the possibility of developing arterial hypotension or dizziness, which may affect driving and working with technical equipment.

Interaction

Concomitant use is not recommended

Lithium preparations. With the simultaneous use of lithium preparations and ACE inhibitors, cases of reversible increases in the concentration of lithium in the blood serum have been reported. Concomitant use of thiazide diuretics may increase the concentration of lithium in the blood plasma and the risk of its toxic effect while taking an ACE inhibitor.

The simultaneous use of Co-Perineva® with lithium preparations is not recommended. If concurrent use is necessary, serum lithium concentrations should be carefully monitored.

Concomitant use requiring special caution

Baclofen - potentiation of the hypotensive effect. It is necessary to monitor blood pressure, renal function and, if necessary, adjust the dose of antihypertensive drugs.

NSAIDs, incl. high doses of acetylsalicylic acid (more than 3 g/day). The simultaneous use of ACE inhibitors with NSAIDs (including acetylsalicylic acid in doses that have an anti-inflammatory effect, COX-2 inhibitors and non-selective NSAIDs) reduces the hypotensive effect of ACE inhibitors, increases the risk of developing renal dysfunction, including the development of acute renal failure, increases serum potassium levels blood, especially in patients with pre-existing renal impairment.

This combination is recommended to be used with caution, especially in elderly patients. Before starting treatment, patients need to compensate for fluid loss, as well as regularly monitor kidney function both at the beginning of therapy and during treatment.

Concomitant use requiring caution

Tricyclic antidepressants, antipsychotics (neuroleptics). They enhance the hypotensive effect and increase the risk of developing orthostatic hypotension (additive effect).

GCS, tetracosactide. Reducing the hypotensive effect (retention of fluid and sodium ions as a result of the action of corticosteroids).

Other antihypertensive drugs: the hypotensive effect of Co-Perineva® may be enhanced.

Perindopril

Concomitant use is not recommended

Potassium-sparing diuretics (spironolactone, triamterene, amiloride, eplerenone) and potassium supplements: ACE inhibitors reduce diuretic-induced renal potassium loss. When used together with ACE inhibitors, it is possible to increase the potassium content in the blood serum, including death. If simultaneous use of an ACE inhibitor and the above drugs is necessary (in case of confirmed hypokalemia), caution should be exercised and regular monitoring of potassium levels in the blood plasma and ECG parameters should be carried out.

Concomitant use requiring special caution

Oral hypoglycemic agents (sulfonylureas) and insulin: the use of ACE inhibitors (described for captopril and enalapril) in very rare cases may enhance the hypoglycemic effect of sulfonylureas and insulin in patients with diabetes mellitus; with their simultaneous use, it is possible to increase glucose tolerance and reduce the need for insulin, which may require dose adjustment of oral hypoglycemic agents and insulin.

Concomitant use requiring caution

Allopurinol, cytostatic immunosuppressants, corticosteroids (for systemic use) and procainamide: simultaneous use of these drugs with ACE inhibitors may increase the risk of developing leukopenia.

General anesthetics: ACE inhibitors may enhance the hypotensive effect of some general anesthetics.

Diuretics (thiazide and loop): the use of diuretics in high doses can lead to hypovolemia (due to a decrease in blood volume), and the addition of perindopril to therapy can lead to a pronounced decrease in blood pressure.

Indapamide

Concomitant use requiring special caution

Drugs that cause ari: because there is a risk of developing hypokalemia, indapamide should be used with caution simultaneously with drugs that can cause ventricular tachycardia of the “pirouette” type, such as: antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide, amiodarone, dofetilide, ibutilide, bretylium tosylate, sotalol); some antipsychotics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol), other antipsychotics (pimozide); other drugs, such as bepridil, cisapride, difemanil methyl sulfate, erythromycin for IV use, halofantrine, mizolastine, moxifloxacin, pentamidine, sparfloxacin, vincamine for IV use, methadone, astemizole, terfenadine. Concomitant use with the above drugs should be avoided. It is necessary to monitor the potassium content in the blood serum to avoid hypokalemia, the development of which requires its correction, and to monitor the QT interval on the ECG.

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

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

Concomitant use requiring caution

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

Iodinated contrast media: Patients with hypovolemia while receiving diuretics have an increased risk of developing acute renal failure, especially when using contrast media containing high doses of iodine. Before using iodine-containing contrast agents, the blood volume should be replenished.

Preparations containing calcium salts: with simultaneous use, hypercalcemia may develop due to a decrease in calcium excretion by the kidneys.

Cyclosporine: it is possible to increase the concentration of creatinine in the blood plasma without changing the concentration of cyclosporine in the blood plasma, even in the absence of pronounced loss of sodium ions and dehydration.

Directions for use and doses

Orally, 1 time per day, preferably in the morning before breakfast, with a sufficient amount of liquid.

If possible, taking the drug should begin with selecting doses of single-component drugs. If clinically necessary, it is possible to prescribe combination therapy with Co-Perineva® immediately after monotherapy.

Doses are given for the indapamide/perindopril ratio.

The initial dose is 1 tablet. drug Co-Perineva® (0.625 mg/2 mg) 1 time per day. If after 1 month of taking the drug it is not possible to achieve adequate blood pressure control, the dose of the drug should be increased to 1 table. drug Co-Perineva® (1.25 mg/4 mg) 1 time per day.

If necessary, to achieve a more pronounced hypotensive effect, it is possible to increase the dose of the drug to the maximum daily dose of Co-Perineva® - 1 table. (2.5 mg/8 mg) 1 time per day.

Elderly patients. Initial dose - 1 tablet. Co-Perineva® drug 0.625 mg/2 mg 1 time per day. Treatment with the drug should be prescribed after monitoring renal function and blood pressure.

Patients with impaired renal function. The drug Co-Perineva® is contraindicated in patients with severe renal failure (Cl creatinine less than 30 ml/min) (see “Contraindications”).

Patients with moderately severe renal failure (creatinine clearance 30–60 ml/min) are recommended to begin therapy with the required doses of drugs (in monotherapy) included in the Co-Perineva® drug; The maximum daily dose of Co-Perineva® is 1.25 mg/4 mg.

Patients with creatinine Cl equal to or greater than 60 ml/min do not require dose adjustment. During therapy, it is necessary to regularly monitor the concentration of creatinine and potassium levels in the blood serum.

Patients with impaired liver function. The drug is contraindicated in patients with severe liver failure (see "Contraindications"). For moderately severe liver failure, no dose adjustment is required.

Children and teenagers. The drug Co-Perineva® should not be used by children and adolescents under 18 years of age, because Data on efficacy and safety are insufficient.

Features of the drug Perineva

Perineva is a drug from the category of ACE inhibitors, which is widely used in the treatment of cardiovascular diseases. The drug for stabilizing blood pressure has two dosage forms - 4 and 8 mg. It has a cumulative effect and can be taken for several years.

The medication has a balanced and safe composition, therefore it is well tolerated and rarely causes side effects. Most often, they appear at the very beginning of therapy and disappear on their own, without requiring medical intervention.

The main advantages of the medicine:

• normalizes blood pressure levels, maintaining effectiveness for up to 24 hours;
• increases myocardial endurance to physical activity;
• minimizes the risk of ischemic and hemorrhagic stroke;
• reduces the likelihood of complications with angina pectoris.

The active components included in Perinev help reduce the incidence of disorders in the cardiovascular system, as well as myocardial infarction and deterioration of cognitive functions.

Very rarely, Perineva can cause side effects in the form of headaches, tinnitus, cough, bronchospasm, allergic skin rashes, shortness of breath, abdominal pain, and attacks of nausea.

Overdose

Symptoms: marked decrease in blood pressure, nausea, vomiting, muscle cramps, dizziness, drowsiness, confusion, oliguria up to anuria (due to a decrease in blood volume); disturbances in water and electrolyte balance are possible (low sodium and potassium levels in the blood plasma).

Treatment: gastric lavage and/or administration of activated carbon, restoration of water and electrolyte balance in a hospital setting. If there is a pronounced decrease in blood pressure, it is necessary to transfer the patient to a supine position with his legs raised up; then measures should be taken aimed at increasing the volume of blood volume (administration of 0.9% sodium chloride solution intravenously). Perindoprilat, the active metabolite of perindopril, can be removed from the body by dialysis.