CO-PERINEVA PILLS 2.5 MG + 8 MG

Ko-Perineva

Clinico-pharmacological group

Antihypertensive drug

Mechanism of action

Combined antihypertensive drug containing an ACE inhibitor - Perindopril and thiazide-like diuretic - Indapamide. The drug has antihypertensive, diuretic and vasodilating action.

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

Antihypertensive effect persists for 24 hours.

A steady decrease in blood pressure is achieved within 1 month on the background of the use of the drug Ko-Perinev® without increasing heart rate. Termination of treatment does not lead to the development of withdrawal syndrome.

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

Perindopril acts through its main active metabolite, perindoprilat. His other metabolites are inactive.

The action of perindopril leads to the expansion of the veins (decrease in the preload on the heart), due to a change in the metabolism of prostaglandins; reduction of OPSS (reduction of afterload on the heart).

In patients with heart failure, perindopril helps reduce the filling pressure of the left and right ventricles; increase in cardiac output and cardiac index; increased regional blood flow in the muscles.

Perindopril is effective for hypertension of any severity: mild, moderate, and severe.

The maximum antihypertensive effect develops after 4-6 hours after a single ingestion and persists for a day.

Termination of therapy does not lead to the development of "withdrawal" syndrome.

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

Indapamide refers to a sulfonamide derivative, is a diuretic. Inhibits sodium reabsorption 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.Possessing the ability to selectively block slow Calcium channels, indapamide increases the elasticity of the artery walls and lowers the CRIA. It has a hypotensive effect in doses that do not have a pronounced diuretic effect. Increasing the dose of indapamide does not entail an increase in the antihypertensive effect, but increases the risk of developing adverse events.

Indapamide in patients with arterial hypertension has no effect on lipid metabolism - TG, LDL and HDL; on the metabolism of carbohydrates, even in patients with diabetes mellitus and arterial hypertension.

Pharmacokinetics

Combined use of perindopril and indapamide does not change their pharmacokinetic parameters, compared with the separate intake of these drugs.

Perindopril

Suction

After oral administration, perindopril is rapidly absorbed from the gastrointestinal tract. Bioavailability is 65-70%. T1/2 perindopril from blood plasma is 1 h. Cmax in blood plasma is achieved within 3-4 hours after ingestion.

Eating reduces the conversion of perindopril to perindopril and the bioavailability of perindopril, so it should be taken 1 time per day in the morning before breakfast. When taking perindopril 1 time / day Css achieved within 4 days.

Distribution

Plasma protein binding of perindoprilat is dose-dependent and is 20%. Perindoprilat easily passes through histohematogenous barriers, excluding the BBB. In small quantities penetrates the placental barrier and is excreted in breast milk. Does not accumulate.

Metabolism

In the liver it is metabolized to form the active metabolite of perindoprilat.In addition, 5 more inactive metabolites are formed.

Removal

T1/2 perindopril from blood plasma is 1 h. T1/2 perindoprilata is about 17 hours. It is excreted by the kidneys.

Pharmacokinetics in special clinical situations

In elderly patients, in patients with renal and heart failure, the elimination of perindoprilat is delayed.

The dialysis clearance of perindoprilat is 70 ml / min.

Perindopril kinetics changed in patients with cirrhosis of the liver: the hepatic clearance is reduced by half. However, the amount of perindoprilat formed does not decrease, which does not require dose adjustment.

Indapamide

Suction

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.

Distribution

Plasma protein binding is 79%. Does not accumulate.

Metabolism

Metabolized in the liver.

Removal

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.

Indapamide

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.

Overdose

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

Ko-Perineva®

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.