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CO-PERINEVA PILLS 1.25MG + 4MG - 30 tabs



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Clinico-pharmacological group



After ingestion quickly and almost completely absorbed from the gastrointestinal tract. Food intake slows down the absorption somewhat, but does not significantly affect the amount of indapamide absorbed. After ingestion in a single dose of Cmax in blood plasma is achieved after 1 h.


Plasma protein binding is 79%. Does not accumulate.


Metabolized in the liver.


T1/2 ranges from 14 to 24 hours (an average of 18 hours). Excreted by the kidneys (70%) mainly in the form of metabolites (the fraction of unchanged drug is about 5%) and the intestine with bile in the form of inactive metabolites (22%).

Pharmacokinetics in special clinical situations

In patients with renal failure, the pharmacokinetic parameters of indapamide do not change significantly.

Indications for use of the drug

- arterial hypertension.

Dosage and administration

Assign inside 1 time / day, preferably in the morning before breakfast, drinking plenty of fluids.

Doses are given for the ratio of perindopril / indapamide.

Initial dose of Ko-Perinev® - 2 mg / 625 mg (1 tab.) 1 time / day. If after 1 month of taking the drug it is not possible to achieve adequate blood pressure control, then the dose of the drug should be increased to 4 mg / 1.25 mg (1 tab.) 1 time / day.

For elderly patients initial dose of Ko-Perinev® makes 2 mg / 625 mg (1 tab.) 1 time / day.

Patients with renal insufficiency (CC 60 ml / min or more) dose adjustment is not required. For patients with CC 30-60 ml / min maximum dose of Ko-Perinev® makes 2 mg / 625 mg (1 tab.) 1 time / day. At QC less than 30 ml / min Co-Perinev® contraindicated.

Patients with moderate liver dysfunction dose adjustment is not required.

Side effect

Classification of the incidence of side effects (WHO): very often (> 1/10), often (from> 1/100 to <1/10), infrequently (from> 1/1000 to <1/100), rarely (from> 1/10 000 to <1/1000), very rarely (from <1/10 000, including individual messages).

Hemic and lymphatic: very rarely - hemorrhagic vasculitis, hemolytic anemia; with long-term use in high doses - thrombocytopenia, leukopenia / neutropenia, agranulocytosis, aplastic anemia, which was recorded while taking ACE inhibitors (patients on hemodialysis or peritoneal dialysis).

Nervous system: often - paresthesias, headache, dizziness, vertigo, asthenia; infrequently - mood lability, sleep disturbances, increased sweating; very rarely - confusion

Special senses: often - visual disturbances, tinnitus.

Since the cardiovascular system: often - pronounced decrease in blood pressure, orthostatic hypotension; very rarely - arrhythmias, incl. bradycardia, ventricular tachycardia, atrial flutter, angina pectoris, myocardial infarction or stroke, possibly secondary, due to severe hypotension in high-risk patients.

On the part of the respiratory system: often - dry, irritating, persistent nature of cough, passing after drug withdrawal, shortness of breath; infrequently - 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, changes in taste, vomiting, dyspepsia, diarrhea; very rarely - pancreatitis, jaundice (cytolytic or cholestatic); frequency not established in liver failure, there is a likelihood of hepatic encephalopathy, intestinal edema.

From the musculoskeletal system: often - muscle cramps.

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

From the reproductive system: infrequently - impotence.

Dermatological reactions: often - pruritus, maculo-papular rash; in rare cases, photosensitivity reactions.

Allergic reactions: infrequently - angioedema of the face, mucous membranes of the oral cavity, tongue, uvula of the upper palate, and / or larynx, urticaria; in patients with burdened allergological anamnesis - mainly dermatological hypersensitivity reactions, purpura; possible exacerbation of systemic lupus erythematosus; very rarely - erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome.

From the laboratory indicators: hypokalemia; hyponatremia with hypovolemia, leading to a decrease in bcc and orthostatic hypotension; increasing the concentration of uric acid and glucose in the serum; a slight increase in plasma creatinine and urea concentrations, reversible after cessation of therapy, which often develops on the background of renal artery stenosis or arterial stenosis of a single kidney, hypertension during diuretic therapy, and renal failure; a transient increase in sodium in the blood plasma; hypochloraemia; proteinuria; rarely - hypercalcemia.

Contraindications to the use of the drug

- angioedema in history (hereditary, idiopathic or angioedema due to the use of ACE inhibitors);

- renal failure severe (CC less than 30 ml / min);

- azotemia;

- anuria;

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

- chronic heart failure in the stage of decompensation;

- refractory hyperkalemia;

- hereditary galactosemia, lactase deficiency, glucose-galactose malabsorption;

- age up to 18 years (efficiency and safety have not been established);

- severe liver failure (including with encephalopathy);

- pregnancy;

- lactation period;

- hypersensitivity to the drug.

WITH caution the drug should be used for systemic diseases of the connective tissue (including systemic lupus erythematosus, scleroderma), against the background of therapy with immunosuppressants (risk of developing neutropenia, agranulocytosis), with inhibition of bone marrow hematopoiesis, reducing BCC (diuretic administration, salt-free diet, vomiting, diarrhea ), with angina, cerebrovascular diseases, renovascular hypertension, diabetes mellitus, chronic heart failure (functional class IVY NYHA classification), with hyperuricemia (especially gout and urate nephrolithiasis), blood pressure lability, with hemodialysis using high-flow polyacrylonitrile membranes (risk of developing anaphylactoid reactions), before the procedure of LDL apheresis, along with desensitizing therapy with allergens (for example, with desensitizing allergens (for example, with desensitizing allergens (for example, with desensitizing allergens) and / or mitral valve, hypertrophic obstructive cardiomyopathy, simultaneously with drugs, extending the QT interval, in elderly patients.

Use of the drug during pregnancy and lactation

Use of the drug Ko-Perinev is contraindicated® during pregnancy. Taking the drug during pregnancy can cause placental ischemia with the risk of slowing the development of the fetus.

The use of the drug Ko-Perinev is not recommended.® during lactation (indapamide is excreted in breast milk). If necessary, use of the drug Ko-Perinev® during lactation, breastfeeding should be discontinued.

Application for violations of the liver

Contraindicated: severe liver failure (including with encephalopathy).

Application for violations of kidney function

Patients with renal insufficiency (CC 60 ml / min or more) dose adjustment is not required. For patients with CC 30-60 ml / min maximum dose of Ko-Perinev® is 2 mg / 625 mg (1 tab.) 1 time / day. At QC less than 30 ml / min Co-Perinev® contraindicated.

special instructions


The simultaneous use of the drug Ko-Perinev is not recommended.® with lithium preparations.

Therapy with Ko-Perinev® contraindicated in patients with severe renal failure (CC less than 30 ml / min). In some patients with arterial hypertension without previous renal dysfunction during therapy with Ko-Perinev® possible symptoms of acute renal failure. In this case, treatment with Ko-Perinev® should stop.In the future, you can resume combination therapy using low doses of the drug Ko-Perinev.®, or use drugs perindopril and indapamide in monotherapy. Such patients need regular monitoring of serum potassium and creatinine every 2 weeks after the start of therapy and every subsequent 2 months of therapy with Co-Perineva ®.

Acute renal failure often develops in patients with severe chronic heart failure or an initial renal dysfunction, including with bilateral stenosis of the renal arteries or stenosis of the artery of the only functioning kidney. Taking the drug Ko-Perinev® not recommended for patients with bilateral renal artery stenosis or arterial stenosis of a single functioning kidney.

Hyponatremia is associated with the risk of a sudden decrease in blood pressure (especially in patients with bilateral renal artery stenosis or arterial stenosis of the only functioning kidney). Therefore, in the dynamic monitoring of patients should pay attention to possible symptoms of dehydration and a decrease in the content of electrolytes in the blood plasma, for example, after prolonged diarrhea or vomiting. Such patients require regular monitoring of electrolytes in the blood plasma. With a marked decrease in blood pressure may be required in / in the introduction of a 0.9% solution of sodium chloride.

Transient hypotension is not a contraindication for further continuation of therapy.After restoring BCC and blood pressure, you can resume therapy with Ko-Perinev®, using low doses of the drug, or using perindopril and indapamide in monotherapy..


Patients taking ACE inhibitors may develop neutropenia / agranulocytosis, thrombocytopenia, and anemia. In patients with normal renal function in the absence of other complications, neutropenia rarely develops and passes on its own after discontinuation of ACE inhibitors.

Perindopril should be used with great caution in patients with diseases of the connective tissue and at the same time receiving immunosuppressive therapy, Allopurinol or procainamide, especially for existing disorders of renal function. Such patients may develop severe infection that is not susceptible to intensive antibiotic therapy. In the case of perindopril, it is recommended to periodically monitor the number of leukocytes in the blood.The patient should be warned that in the event of any signs of an infectious disease (sore throat, fever), you should immediately consult a doctor.

When taking ACE inhibitors, incl. perindopril, in rare cases, angioedema of the face, lips, tongue, uvula, and / or larynx may develop. When these symptoms occur, the drug should be immediately discontinued. The patient’s condition should be monitored until the signs of edema disappear completely.

If angioedema affects only the face and lips, then its manifestations usually disappear on their own or antihistamines can be used to treat symptoms. Angioedema, accompanied by swelling of the tongue or larynx, can lead to airway obstruction and death.

If symptoms of angioedema appear, you should immediately enter the subcutaneous epinephrine (adrenaline) at a dilution of 1: 1000 (0.3 or 0.5 ml) and / or ensure the airway is passable.

In patients with a history of angioedema, not associated with taking ACE inhibitors, the risk of its development may be increased when taking drugs in this group.

In rare cases, against the background of therapy with ACE inhibitors, angioedema of the intestines develops. At the same time, patients have abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without prior angioedema of the face and at a normal level of C-1 esterase.The diagnosis is established using computed tomography of the abdominal cavity, ultrasound, or at the time of surgical intervention. Symptoms disappear after discontinuation of ACE inhibitors. In patients with abdominal pain, receiving ACE inhibitors, when conducting a differential diagnosis, it is necessary to take into account the possibility of developing angioedema.

There are separate reports on the development of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with hymenoptera venom (bees, wasps). ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. The use of an ACE inhibitor in patients receiving immunotherapy with hymenoptera poison should be avoided. However, the development of anaphylactoid reactions can be avoided by temporarily canceling the ACE inhibitor no less than 24 hours before the desensitization procedure begins.

In rare cases, patients receiving ACE inhibitors may experience life-threatening anaphylactoid reactions when performing an apheresis of LDL using dextran sulfate. To prevent an anaphylactoid reaction, the ACE inhibitor therapy should be discontinued before each LDL apheresis procedure using high-flow membranes.

In patients receiving ACE inhibitors during hemodialysis using high-flow membranes (for example, AN69®) anaphylactoid reactions were noted. Therefore, it is desirable to use a different type of membrane or use a hypotensive drug of another pharmacotherapeutic group.

The combined use of perindopril and potassium-saving diuretics, as well as preparations of potassium and potassium-containing substitutes for table salt is not recommended.

During therapy with an ACE inhibitor, a dry cough may occur, which disappears after discontinuation of drugs of this group. With the appearance of dry cough, you should remember about the possible connection of this symptom with taking an ACE inhibitor. If the doctor believes that therapy with an ACE inhibitor is necessary for the patient, taking the drug Ko-Perinev® can be continued.

With cirrhosis of the liver, accompanied by edema and ascites, arterial hypotension, chronic heart failure, a significant activation of the RAAS is possible, especially with severe hypovolemia and a decrease in the content of electrolytes in the blood plasma (on the background of a salt-free diet or long-term use of diuretics).

The use of an ACE inhibitor causes a blockade of the RAAS, therefore, a sharp decrease in blood pressure and / or an increase in serum creatinine is possible, indicating the development of acute renal failure, which is more often observed when taking the first dose of Ko-Perinev® or during the first 2 weeks of therapy.

In elderly patients before starting the administration of the drug Ko-Perinev® kidney function and plasma potassium should be evaluated. Initial dose of Ko-Perinev® selected depending on the degree of reduction in blood pressure, especially with a decrease in BCC and in chronic heart failure (IV functional class according to the NYHA classification). Such measures help to avoid a sharp decrease in blood pressure.

The risk of arterial hypotension exists in all patients, however, special care should be taken when using the drug Ko-Perinev® in patients with coronary artery disease and cerebrovascular insufficiency. In such patients, drug treatment should begin with a dose of 2 mg / 625 µg (initial dose).

In patients with diagnosed or suspected renal artery stenosis, treatment with Ko-Perinev® It should be started in the hospital with a dose of 2 mg / 625 µg under the control of kidney function and the content of potassium in the blood plasma. Some patients may develop acute renal failure, which is reversible after drug withdrawal.

In patients with chronic heart failure (NYHA classification, IV functional class), treatment with Ko-Perinev® You must start with an initial dose of 2 mg / 625 mcg under medical supervision.

When prescribing the drug Ko-Perinev® Patients with diabetes who receive hypoglycemic agents for oral administration or insulin, during the first month of therapy should regularly monitor the concentration of glucose in the blood.

Perindopril (as well as other ACE inhibitors), has a less pronounced hypotensive effect in patients of the Negroid race compared with other races.

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

It is recommended to stop taking ACE inhibitors, incl. perindopril, 12 hours before surgery, warning the anesthesiologist about the use of ACE inhibitors.

ACE inhibitors should be used with caution in patients with obstruction of the left ventricular outflow tract and with aortic and / or mitral stenosis.

In rare cases, in patients receiving ACE inhibitors, cholestatic jaundice occurs, with the progression of which fulminant necrosis of the liver develops, sometimes with a fatal outcome. With the appearance of jaundice or a significant increase in the activity of hepatic transaminases on the background of taking ACE inhibitors, taking the drug Ko-Perinev® should stop.

Patients after kidney transplantation or in patients on hemodialysis may develop anemia.

During treatment with ACE inhibitors, incl. and perindopril may develop hyperkalemia. Risk factors for hyperkalemia are renal failure, advanced age, diabetes mellitus, some concomitant conditions (decreased BCC,acute heart failure at the stage of decompensation, metabolic acidosis), simultaneous administration of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), as well as potassium or potassium-containing salt substitutes and the use of other drugs that increase the content of potassium in the blood plasma (for example, heparin). Hyperkalemia can lead to serious heart rhythm disturbances, sometimes fatal. The combined use of the above preparations must be carried out with caution.


There are reports of cases of increased photosensitivity in patients receiving thiazide and thiazide-like diuretics. With the development of the photosensitivity reaction while taking the drug Ko-Perinev® treatment must be stopped. If necessary, resume the use of the drug Ko-Perinev®, open skin should be protected from direct exposure to sunlight and artificial UV rays.

Before starting treatment with Ko-Perinev® it is necessary to determine the content of sodium in the blood plasma and, while taking the drug, conduct regular monitoring of electrolytes in the blood plasma. All diuretics can cause hyponatremia, leading to serious complications.

Therapy with thiazide and thiazide-like diuretics is associated with the risk of hypokalemia (less than 3.4 mmol / l) in elderly patients, exhausted patients, patients with cirrhosis of the liver, patients with peripheral edema, ascites, ischemic heart disease, and chronic heart failure.Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of arrhythmia. High-risk patients include patients with an extended QT interval on an ECG. Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, especially ventricular pirouette arrhythmias, which can be fatal. In all the cases described, regular monitoring of potassium in the blood plasma is necessary. The first determination of the content of potassium in the blood plasma should be carried out during the first week from the start of therapy with Ko-Perinev®.

Thiazide and thiazide-like diuretics reduce the excretion of calcium by the kidneys, leading to a slight and temporary increase in plasma calcium levels. Severe hypercalcemia may be due to latent hyperparathyroidism. Before studying the function of the parathyroid glands, you should stop taking the drug Ko-Perinev®.

Glucose concentration should be monitored in patients with diabetes.

In patients with an increased concentration of uric acid in the blood plasma during therapy with Ko-Perinev® may increase the frequency of exacerbation of gout.

Hypovolemia as a result of lowering the BCC or hyponatremia caused by taking diuretics at the beginning of treatment with Co-Perineva® can lead to a decrease in glomerular filtration rate and is accompanied by an increase in plasma creatinine and urea.

Indapamide can give a false positive reaction during doping control.

Use in pediatrics

Co-Perineva drug® contraindicated children and adolescents under 18 due to lack of data on efficacy and safety of use.

Influence on ability to drive motor transport and control mechanisms

Care must be taken when driving vehicles and other technical devices that require increased attention and speed of psychomotor reactions.


Symptoms: pronounced decrease in blood pressure, nausea, vomiting, muscle cramps, dizziness, drowsiness, confusion, oliguria up to anuria (due to a decrease in the BCC); possible violations of water and electrolyte balance (low sodium and potassium in the blood plasma).

Treatment: gastric lavage and / or the appointment of Activated carbon, the restoration of water and electrolyte balance in the hospital. With a pronounced decrease in blood pressure, it is necessary to transfer the patient to a supine position with their legs elevated; then it is necessary to carry out measures aimed at increasing the bcc (introduction of a 0.9% solution of sodium chloride in / in). Perindoprilat, the active metabolite of perindopril, can be eliminated from the body through dialysis.

Drug interaction


Simultaneous use is not recommended.

With the simultaneous use of lithium preparations and ACE inhibitors, there have been cases of a reversible increase in the concentration of lithium in the blood serum.

Simultaneous administration of thiazide diuretics may contribute to an increase in the concentration of lithium and the risk of its toxic action in the presence of an ACE inhibitor.

Simultaneous use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), potassium preparations or potassium-containing salt substitutes, as well as the use of other drugs that increase the plasma potassium level (eg, heparin) increases the risk of hyperkalemia.<

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