Co-Dalneva pills 5mg+2.5mg+8mg, 90pcs

Composition

Per 1 tablet 5 mg + 2.5 mg + 8 mg

Active ingredients:

Amlodipine Bezilate (amlodipine besilate) 6,935 mg, equivalent to Amlodipine 5,000 mg Indapamide 2,500 mg

Perindoprilaerbumin B, substance-granules 40,824 mg

[Active ingredient of substance-granules:  Perindoprilaerbumin 8,000 mg

Excipients of the granule substance:  microcrystalline cellulose, calcium chloride hexahydrate]

Auxiliary substances:  microcrystalline cellulose, pregelatinized starch, sodium carboxymethyl starch, sodium bicarbonate, colloidal silicon dioxide, magnesium stearate.

Pharmacological action

Ko-Dalneva® is a combination drug containing perindoprilaerbumin (an angiotensin-converting enzyme (ACE) inhibitor), indapamide (a thiazide-like diuretic) and amlodipine (a slow calcium channel blocker).

The drug Ko-Dalneva ® combines the properties of each of the active substances, which have a potentiating effect.

Pharmacodynamics

Amlodipine

Amlodipine – BMCC, a dihydropyridine derivative. Amlodipine inhibits the transmembrane transfer of calcium ions to cardiomyocytes and smooth muscle cells of the vascular wall. The antihypertensive effect of amlodipine is due to the direct relaxing effect on smooth muscle cells of the vascular wall. The mechanism of antianginal action of amlodipine is not fully understood, presumably it is associated with the following effects: :

• causes dilation of peripheral arterioles, reducing total peripheral vascular resistance – OPSS) – afterload, which leads to a decrease in myocardial oxygen demand;

• causes dilation of coronary arteries and arterioles in both intact and ischemic areas of the myocardium, which increases oxygen supply to the myocardium, including in patients with Prinzmetal angina pectoris.

In patients with arterial hypertension (AH), taking amlodipine once a day provides a clinically significant reduction in blood pressure (BP) (in the “lying” and “standing” positions) within 24 hours. The antihypertensive effect develops slowly, and therefore the development of acute arterial hypotension is uncharacteristic.

In patients with angina pectoris, taking amlodipine once a day increases exercise tolerance, the time to develop an angina attack and to “ischemic” ST-segment depression, reduces the frequency of angina attacks and the need for nitroglycerin (short-acting forms). Amlodipine does not affect the lipid profile and does not cause changes in the lipid-lowering parameters of blood plasma. The drug can be used in patients with bronchial asthma( BA), diabetes mellitus (DM) and gout.

Indapamide

Indapamide is a sulfonamide derivative Pharmacological properties are similar to thiazide diuretics. Indapamide inhibits the reabsorption of sodium ions in the cortical segment of the Henle loop, which leads to an increase in renal excretion of sodium and chlorine ions, and to a lesser extent potassium and magnesium ions, thereby increasing diuresis and lowering blood pressure.

In the monotherapy mode, the antihypertensive effect persists for 24 hours and is manifested when the drug is used in doses that have a minimal diuretic effect. The antihypertensive effect of indapamide is associated with an improvement in the elastic properties of large arteries, a decrease in OPSS. Left ventricular hypertrophy (LVH) decreases with indapamide.

Indapamide does not affect the concentration of lipids in blood plasma (triglycerides, total cholesterol, low-and high-density lipoproteins), on the parameters of carbohydrate metabolism (including in patients with diabetes).

Perindopril

Perindopril is an angiotensin-converting enzyme inhibitor. ACE, or kininase II, is an exopeptidase that converts angiotensin I into a vasoconstrictor substance – angiotensin II, and also destroys bradykinin, which has vasodilating properties, to an inactive heptapeptide.

As a result, perindopril provides the following effects:

* reduces the secretion of aldosterone·

* increases the activity of blood renin plasma according to the principle of “negative” feedback;

· with prolonged use, it reduces the OPSS-afterload of the heart, which is mainly due to the effect on muscle and renal vessels. A decrease in OPSS is not accompanied by sodium and water retention and does not cause reflex tachycardia.

A study of hemodynamic parameters in patients with chronic heart failure (CHF) revealed:  

· reduced filling pressure in the left and right ventricles of the heart;

* reduced OPSS;

· increased cardiac output and cardiac index;

· increased peripheral blood flow in the muscles.

In addition, there was an improvement in the results of the exercise test.

The action of perindopril is carried out through the active metabolite-perindoprilat. Other metabolites do not have an ACE inhibitory effect in vitro.

Perindopril is effective in the treatment of hypertension of any severity, reduces both systolic and diastolic blood pressure in the “lying” and “standing” positions.

The antihypertensive effect reaches its maximum in 4-6 hours after a single oral use and persists for 24 hours.

Antihypertensive effect 24 hours after a single oral dose is about 87-100% of the maximum antihypertensive effect.

Perindopril has an antihypertensive effect in patients with both low and normal plasma renin activity.

The therapeutic effect occurs less than 1 month after the start of therapy and is not accompanied by tachyphylaxis. Discontinuation of therapy does not cause withdrawal symptoms.

Perindopril has vasodilating properties and helps restore the elasticity of large arteries, the structure of the vascular wall of small arteries, and also reduces LVH.

Concomitant use with a thiazide diuretic increases the severity of the antihypertensive effect and reduces the risk of hypokalemia while taking diuretics.

Perindopril / Indapamide

The combination of perindopril/indapamide has a dose-dependent antihypertensive effect on both systolic and diastolic blood pressure (in the “standing” and “lying” positions), regardless of the patient’s age. The antihypertensive effect persists for 24 hours. The therapeutic effect occurs less than 1 month after the start of therapy and is not accompanied by tachyphylaxis. Discontinuation of therapy does not cause withdrawal symptoms.

In clinical studies, the concomitant use of perindopril and indapamide increased the severity of the antihypertensive effect compared to monotherapy with each drug. The combination of perindoprilatertbutylamine (perindopril erbumin)/indapamide resulted in significantly more pronounced LVH reduction than enalapril monotherapy. The most significant effect on LVH is achieved with the use of perindoprilatertbutylamine (perindopril erbumin) 8 mg/indapamide 2.5 mg.

Pharmacokinetics

Amlodipine

Suction, distribution

After oral use, amlodipine is slowly absorbed from the gastrointestinal tract (GI). Food intake does not affect the bioavailability of amlodipine. The maximum concentration (cmax) of amlodipine in blood plasma is reached 6-12 hours after oral use. Absolute bioavailability is about 64-80%. The volume of distribution (Vd) is approximately 21 l/kg. In in vitro studies, the degree of binding of amlodipine to plasma proteins was about 97.5%.

Metabolism, elimination

The final half-life (T_1/2) from the blood plasma is about 35-50 hours, which allows you to take amlodipine 1 time a day. Amlodipine is metabolized in the liver to form inactive metabolites, while 10% of the oral dose of amlodipine is excreted unchanged, about 60% – by the kidneys in the form of metabolites. Amlodipine is not eliminated from the body by hemodialysis.

The time to reach the_cmax of amlodipine does not differ in elderly and younger patients. In elderly patients, there is a decrease in the clearance of amlodipine, which leads to an increase in the area under the concentration-time curve (AUC) and T_1/2. No dose adjustment is required in elderly patients, but increasing the dose of amlodipine should be done with caution. The increase in AUC and T_1/2 in patients with CHF corresponds to the expected value for this age group.

In patients with impaired renal function, changes in the concentration of amlodipine in blood plasma do not correlate with the degree of renal failure. A slight extension of T_{1/2 is possible.}

In patients with impaired liver function, data on the use of amlodipine are limited, there is a decrease in the clearance of amlodipine, which leads to an increase in T_1/2 and AUC by about 40-60%.

Indapamide

Suction, distribution

Indapamide is rapidly and completely absorbed from the gastrointestinal tract. _cmax in blood plasma is reached approximately 1 hour after oral use of the drug. The degree of binding to plasma proteins is 79%.

Metabolism, elimination

of T_1/2 is 14-24 hours (average 18 hours). Repeated use of indapamide does not lead to its accumulation. It is eliminated mainly by the kidneys (70% of the oral dose) and through the intestine (22%) in the form of inactive metabolites.

The pharmacokinetics of indapamide do not change in patients with renal insufficiency.

Perindopril

Absorption, metabolism

When taken orally, perindopril is rapidly absorbed. Cmax in blood plasma is reached 1 hour after oral use.

Perindopril is a prodrug, i. e. it has no pharmacological activity. About 27% of the oral dose of perindopril enters the bloodstream as the active metabolite, perindoprilat. In addition to the active metabolite-perindoprilat,5 more metabolites are formed that do not have pharmacological activity. _{Cmax of}perindoprilat in blood plasma is reached 3-4 hours after oral use.

Food intake slows down the conversion of perindopril to perindoprilate, thus affecting bioavailability. Therefore, perindopril should be taken once a day, in the morning, before meals.

There is a linear dependence of the concentration of perindopril in blood plasma on the dose taken orally.

The Vd distribution

of Free perindoprilate is approximately 0.2 l / kg. The degree of binding of perindoprilat to plasma proteins (mainly with ACE) is about 20% and is dose-dependent.

Elimination

of T_1/2perindopril from blood plasma is 1 hour. Perindoprilat is eliminated from the body by the kidneys. The final T_1/2of the free fraction is about 17 hours, and the equilibrium state is reached within 4 days.

Elimination of perindoprilat is slowed in elderly patients, as well as in patients with heart and renal insufficiency. Dose adjustment in patients with renal insufficiency is carried out taking into account the degree of impaired renal function (creatinine clearance (CC)). The dialysis clearance of perindoprilat is 70 ml / min

. The pharmacokinetics of perindopril vary in patients with cirrhosis of the liver: hepatic clearance decreases by 2 times. However, the amount of perindoprilat produced does not decrease, so no dose adjustment is required (see sections” Dosage and use “and”Special Instructions”).

Indications

Arterial hypertension (if necessary, simultaneous therapy with amlodipine, indapamide and perindopril in doses used in monotherapy of individual components).

Use during pregnancy and lactation

Pregnancy

The drug Ko-Dalneva® is contraindicated during pregnancy (see the section “Contraindications”).

When planning pregnancy or when it occurs while taking Ko-Dalneva®, you should immediately stop taking it and prescribe an alternative antihypertensive therapy with a proven safety profile.

The safety of using amlodipine during pregnancy has not been established. Limited data on the use of amlodipine and other BMCs during pregnancy indicate that there is no negative effect on the fetus. In animal experiments, signs of reproductive toxicity were observed with the use of high doses of amlodipine.

In some patients treated with BMCC, a reversible decrease in sperm motility was observed. There is insufficient clinical evidence regarding the potential effect of amlodipine on reproductive function.

Data on the use of indapamide in pregnant women are not available or limited (less than 300 cases). 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 development delay. In rare cases, newborns develop hypoglycemia and thrombocytopenia while taking diuretics shortly before delivery.

Animal studies have shown no direct or indirect toxic effects on reproductive function.

As a precautionary measure, it is recommended to avoid using indapamide during pregnancy.

The available data on the teratogenicity of ACE inhibitors in the first trimester of pregnancy are not convincing, but this risk cannot be completely excluded. In the second and third trimesters of pregnancy, exposure to ACE inhibitors on the fetus can lead to impaired fetal development (decreased renal function, oligohydramnios, slowing of ossification of cranial cavities) and the development of complications in newborns (renal failure, hypotension, hyperkalemia).

If an ACE inhibitor was used in the second or third trimester of pregnancy, ultrasound examination of the fetal kidneys and skull bones is recommended. Newborns whose mothers were treated with ACE inhibitors during pregnancy need careful medical supervision, as there is a risk of developing arterial hypotension.

Breast-feeding period

Amlodipine is excreted in breast milk. The proportion of maternal dose received by the child was estimated in the interquartile range from 3% to 7%, with a maximum of 15%. The effect of amlodipine on children is unknown. The decision to extend / discontinue breastfeeding or continue / discontinue amlodipine therapy should be made taking into account the benefits of breastfeeding for the child and the benefits of using amlodipine for the mother.

Currently, there is no reliable information about the excretion of indapamide or its metabolites in breast milk.

Taking thiazide diuretics causes a decrease or suppression of lactation in the mother, the newborn may develop hypersensitivity to sulfonamide derivatives, hypokalemia and” nuclear ” jaundice.

Indapamide is contraindicated during breastfeeding.

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

Ko-Dalneva® is contraindicated in breast-feeding. If it is necessary to use the drug Ko-Dalneva® during lactation, breastfeeding should be discontinued.

Contraindications

• Hypersensitivity to amlodipine and other dihydropyridine derivatives, indapamide and other sulfonamide derivatives, perindopril and other ACE inhibitors, as well as to excipients that make up the drug.
• Angioedema (Quincke’s edema) in the anamnesis associated with the use of ACE inhibitors.
• Hereditary / idiopathic angioedema.
• Severe arterial hypotension (systolic blood pressure less than 90 mm Hg).
• Shock, including cardiogenic shock.
• Obstruction of the left ventricular exit tract (for example, clinically significant aortic stenosis).
• Hemodynamically unstable heart failure after acute myocardial infarction.
• Severe renal insufficiency (creatinine clearance less than 30 ml / min).
• Severe hepatic insufficiency, including hepatic encephalopathy.
• Refractory hypokalemia.
• Concomitant use with aliskiren or drugs containing aliskiren in patients with diabetes mellitus and/or moderate to severe renal impairment (glomerular filtration rate (GFR) less than 60 ml/min/1.73 m2 of body surface area).
• Concomitant use with angiotensin II receptor antagonists (ARA II) in patients with diabetic nephropathy.
• Concomitant use with neutral endopeptidase inhibitors (for example, with drugs containing sacubitril) due to a high risk of angioedema (see the section “Interaction with other drugs”).
• extracorporeal methods of treatment using some membranes with a negatively charged surface.

• Severe bilateral renal artery stenosis or renal artery stenosis of the only functioning kidney.

• Pregnancy and lactation (see the section “Use during pregnancy and lactation”).
• Age up to 18 years (efficacy and safety have not been established).

Given the lack of sufficient clinical experience, it is not recommended to use UP in patients undergoing hemodialysis, as well as in patients with untreated heart failure in the decompensation stage.

Interaction

Amlodipine

Simultaneous use is not recommended

Dantrolene (intravenous use)

In laboratory animals, cases of ventricular fibrillation with a fatal outcome and collapse were noted against the background of verapamil and intravenous (iv) dantrolene use, accompanied by hyperkalemia. Due to the risk of developing hyperkalemia, it is recommended to avoid the simultaneous use of BMCC (amlodipine) and dantrolene in patients subject to malignant hyperthermia, as well as in the treatment of malignant hyperthermia.

Simultaneous use that requires special attention

Inducers of the CYP3A4 isoenzyme

With simultaneous use of inducers of the CYP3A4 isoenzyme, the concentration of amlodipine in blood plasma may change. Therefore, it is necessary to monitor blood pressure and adjust the dose both during and after simultaneous use, especially with powerful inducers of the CYP3A4 isoenzyme (for example, rifampicin, St. John’s wort preparations).

Inhibitors of the CYP3A4 isoenzyme

Concomitant use of amlodipine with strong or moderate inhibitors of the CYP3A4 isoenzyme (protease inhibitors, azole antifungal drugs, macrolides, for example, erythromycin or clarithromycin, verapamil or diltiazem) can lead to a significant increase in the concentration of amlodipine, which increases the risk of hypotension. The clinical manifestations of these pharmacokinetic abnormalities may be more pronounced in elderly patients. Therefore, it may be necessary to monitor the clinical condition and adjust the dose.

Mammalian mechanistic target inhibitors of rapamycin (tTOR)

mTOR inhibitors, such as axirolimus, temsirolimus and everolimus, are substrates of the CYP3A isoenzyme. Amlodipine is a weak inhibitor of the CYP3A isoenzyme. When used concomitantly with mTOR inhibitors, amlodipine may increase their exposure.

Clarithromycin

Clarithromycin is an inhibitor of the CYP3A4 isoenzyme. Concomitant use of amlodipine and clarithromycin increases the risk of hypotension.Careful medical monitoring of patients receiving amlodipine concomitantly with clarithromycin is recommended.

Tacrolimus

When co-administered with amlodipine, there is a risk of increasing the concentration of tacrolimus in blood plasma, but the pharmacokinetic mechanism of this interaction is not fully understood. To prevent the toxic effect of tacrolimus when used concomitantly with amlodipine, the concentration of tacrolimus in blood plasma should be monitored and the dose of tacrolimus adjusted if necessary.

Cyclosporine

Drug interaction studies with cyclosporine and amlodipine in healthy volunteers or other patient groups have not been conducted, except for patients who underwent kidney transplantation, who had variable minimum concentrations (average values: 0% -40%) of cyclosporine. When amlodipine is used concomitantly in patients undergoing kidney transplantation, the concentration of cyclosporine in blood plasma should be monitored and, if necessary, its dose should be reduced.

Simvastatin

Simultaneous repeated use of amlodipine at a dose of 10 mg and imvastatin at a dose of 80 mg increases the exposure of simvastatin by 77% compared to that in monotherapy with imvastatin. Patients receiving amlodipine are recommended to use simvastatin at a dose of no more than 20 mg / day.

Simultaneous use that requires attention

Amlodipine enhances the antihypertensive effect of antihypertensive drugs.

Tasonermin

When used concomitantly, amlodipine may increase the systemic exposure of tasonermine in blood plasma. In such cases, it is necessary to regularly monitor the concentration of tasonermin in the blood and adjust the dose if necessary.

Other drug combinations

Cimetidine

Cimetidine does not affect the pharmacokinetics of amlodipine.

Aluminum-or magnesium-containing antacids

A single dose of aluminum-or magnesium-containing antacids does not significantly affect the pharmacokinetics of amlodipine.

Sildenafil

A single dose of 100 mg of sildenafil in patients with essential hypertension does not affect the pharmacokinetics of amlodipine.

In clinical drug interaction studies, amlodipine did not affect the pharmacokinetics of atorvastatin, digoxin, or warfarin.

Concomitant use of amlodipine and consumption of grapefruit or grapefruit juice is not recommended, due to the possible increase in the bioavailability of amlodipine in some patients, which may lead to an increased antihypertensive effect.

Indapamide

Simultaneous use that requires special attention

Drugs that can cause polymorphic ventricular tachycardia of the”pirouette”type

Given the risk of hypokalemia, caution should be exercised when using indapamide concomitantly with drugs that can cause polymorphic ventricular tachycardia of the “pirouette” type, for example, antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide, amiodarone, dofetilide, ibutilide, bretiliatosylate, sotalol), some neuroleptics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluorperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol), other neuroleptics (pimozide), other drugs such as bepridil, cisapride, difemanylamethyl sulfate, intravenous erythromycin, halofantrin, mizolastine, moxifloxacin, pentamidine, sparfloxacin, vincamine iv, methadone, astemizole, terfenadine. Simultaneous use with the above-mentioned drugs should be avoided in the development of hypokalemia, its correction should be carried out, and the ECG (QT interval) should be monitored.

Drugs that can cause hypokalemia

Concomitant use with amphotericin IV, systemic glucocorticosteroids and mineralocorticosteroids, tetracosactide, and laxatives that stimulate gastrointestinal motility increases the risk of hypokalemia (additive effect). It is necessary to monitor the content of potassium in the blood plasma, if necessary – correction of hypokalemia. Special care should be taken when used concomitantly with cardiac glycosides. Laxatives that do not stimulate gastrointestinal motility should be used.

Cardiac Glycosides

Hypokalemia increases the toxic effect of cardiac glycosides. With simultaneous use, the potassium content in the blood plasma and ECG indicators should be monitored and, if necessary, the question of whether to continue therapy should be decided.

Simultaneous use that requires attention

Metformin

Functional renal failure, which may occur while taking diuretics, especially “loop” ones, with simultaneous use of metformin increases the risk of lactic acidosis. Metformin should not be used if the creatinine clearance in blood plasma exceeds 15 mg / l (135 mmol/l) in men and 12 mg/l (110 mmol/l) for women.

Iodine-containing contrast agents

Dehydration of the body while taking diuretics increases the risk of acute renal failure, especially when high doses of iodine-containing contrast agents are administered. Before using iodine-containing contrast agents, it is necessary to compensate for hypovolemia.

Calcium Salts

With simultaneous use, hypercalcemia may develop due to a decrease in the excretion of calcium by the kidneys.

Cyclosporine

It is possible to increase the creatinine clearance in blood plasma without changing the concentration of cyclosporine, even with a normal content of water and sodium.

Perindopril

Data from clinical studies show that double blockade of the RAAS as a result of simultaneous use of ACE inhibitors, ARA II or aliskiren leads to an increased incidence of adverse events such as hypotension, hyperkalemia and impaired renal function (including acute renal failure), compared with situations when only one drug is used that affects the RAAS (see the sections “Pharmacodynamics”, “Contraindications” and “Special Instructions”).

Medications that cause hyperkalemia

Certain medications or classes of medications may increase the incidence of hyperkalemia: aliskiren, potassium salts, potassium-sparing diuretics, ACE inhibitors, ARA II, NSAIDs, heparin, immunosuppressants such as cyclosporine or tacrolimus, medications containing trimethoprim.

Concomitant use with these medications increases the risk of hyperkalemia.

Simultaneous use is contraindicated

Aliskiren

Patients with diabetes mellitus or renal insufficiency have an increased risk of hyperkalemia, deterioration of renal function, increased incidence of adverse events from the cardiovascular system, and mortality from cardiovascular diseases.

Concomitant use of ACE inhibitors with aliskiren or drugs containing aliskiren in patients with diabetes mellitus and / or moderate to severe renal impairment (GFR

Neutral endopeptidase inhibitors

An increased risk of angioedema has been reported with concomitant use of ACE inhibitors and racecadotril (an enkephalinase inhibitor).

Concomitant use of ACE inhibitors with drugs containing sacubitril (a neprilysin inhibitor) increases the risk of angioedema, and therefore the simultaneous use of these drugs is contraindicated. ACE inhibitors should be prescribed no earlier than 36 hours after discontinuation of drugs containing sacubitril. It is contraindicated to prescribe drugs containing sacubitril to patients receiving ACE inhibitors, as well as within 36 hours after discontinuation of ACE inhibitors.

Extracorporeal therapy

Extracorporeal treatments that lead to blood contact with negatively charged surfaces, such as hemodialysis using high-flow membranes (for example, polyacrylonitrile membranes) and LDL apheresis using dextran sulfate, may increase the risk of severe anaphylactoid reactions (see section “Contraindications”). Therefore, it is advisable to use a different type of membrane or use a hypotensive drug of a different pharmacotherapeutic group.

Simultaneous use is not recommended

Aliskiren

Patients without diabetes mellitus or impaired renal function may have an increased risk of hyperkalemia, impaired renal function, and increased incidence of cardiovascular morbidity and mortality.

Double blockade of the renin-angiotensin-aldosterone system in patients with atherosclerosis, CHF, or DM accompanied by damage to target organs is associated with a higher incidence of hypotension, syncope, hyperkalemia, and impaired renal function (including acute renal failure) compared with the use of the drug in one of the listed groups. Double blockade of the RAAS is possible only in some cases with careful monitoring of renal function, potassium content and blood pressure.

Concomitant use of ACE inhibitors with ARA II is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

Estramustin

Concomitant use of ACE inhibitors with estramustine is associated with the risk of angioedema.

Lithium

With the simultaneous use of lithium preparations and ACE inhibitors, a reversible increase in serum lithium content and associated toxic effects may occur. The use of perindopril in combination with indapamide and lithium is not recommended, but if necessary, the content of lithium in the blood serum should be carefully monitored.

Concomitant use of thiazide diuretics may further increase the level of lithium in blood plasma and increase the risk of its toxic effect against the background of taking an ACE inhibitor.

Concomitant use of a combination of perindopril and indapamide with lithium preparations is not recommended. If simultaneous use is necessary, the lithium content in the blood plasma should be carefully monitored.

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

During therapy with ACE inhibitors, the potassium content in the blood plasma, as a rule, remains within the normal range, but hyperkalemia may develop. Concomitant use of potassium-sparing diuretics (triamterene, amiloride), potassium preparations, and potassium-containing salt substitutes can lead to a significant increase in the potassium content in blood plasma. Caution should also be exercised when using perindopril concomitantly with other drugs that increase serum potassium, such as trimethoprim and co-trimoxazole (sulfamethoxazole + trimethoprim), since trimethoprim is known to act similarly to the potassium-sparing diuretic amiloride. If it is necessary to simultaneously take an ACE inhibitor with the above drugs (in the case of hypokalemia), care should be taken and regular monitoring of the potassium content in the blood plasma and ECG parameters should be carried out.

mTOR inhibitors (e. g. sirolimus, everolimus, temsirolimus)

In patients using both an ACE inhibitor and an mTOR inhibitor, therapy may be associated with an increased risk of angioedema.

Simultaneous use that requires special attention

Nonsteroidal anti-inflammatory drugs (NSAIDs), including high doses of acetylsalicylic acid (ASA) (more than 3 g / day)

Concomitant use of ACE inhibitors with NSAIDs (including ASA at a dose that has an anti-inflammatory effect, cyclooxygenase-2 (COX-2) inhibitors and non-selective NSAIDs) may lead to a decrease in the antihypertensive effect, as well as to deterioration of renal function, including the development of acute renal failure, and an increase in blood potassium content, especially in patients with reduced renal function. Caution should be exercised when using this combination, especially in elderly patients. Patients should be compensated for fluid loss and have their kidney function monitored regularly both at the start of treatment and during treatment.

Hypoglycemic agents (insulin, hypoglycemic agents for oral use)

Epidemiological studies have shown that the simultaneous use of ACE inhibitors and hypoglycemic agents (insulin, hypoglycemic agents for oral use) can increase the hypoglycemic effect of insulin and hypoglycemic agents for oral use, up to the development of hypoglycemia. This effect is most likely observed during the first weeks of concomitant therapy, as well as in patients with impaired renal function.

Potassium-sparing diuretics

Patients taking diuretics, especially those that remove fluids and/or salts, may experience a significant decrease in blood pressure at the beginning of ACE inhibitor therapy. The risk of developing an antihypertensive effect can be reduced by discontinuing the diuretic, replacing the loss of fluid or salts before starting therapy with perindopril, and prescribing a low dose of perindopril with a gradual increase.

In hypertensive patients with previous diuretic therapy, which may have resulted in excessive fluid and/or salt excretion, diuretics should be discontinued prior to the use of ACE inhibitors (while a potassium-sparing diuretic may be prescribed again later) or start treatment with a low-dose ACE inhibitor with a gradual increase.

When using diuretics for the treatment of CHF, an ACE inhibitor should be prescribed at a very low dose, possibly after reducing the dose of the potassium-sparing diuretic used simultaneously.

In all cases, renal function (creatinine concentration) should be monitored during the first weeks of use of an ACE inhibitor.

Potassium-sparing diuretics (eplerenone, spironolactone)

Use of Eplerenone or spironolactone in doses from 12.5 mg to 50 mg per day and low doses of ACE inhibitors: in the treatment of NYHA functional class II-IV heart failure with left ventricular ejection fraction

Before using this combination of medications, it is necessary to make sure that there is no hyperkalemia and renal failure.

It is necessary to regularly monitor the concentration of creatinine and potassium in the blood plasma weekly in the first month of therapy and monthly thereafter.

Concomitant use requiring attention

Allopurinol, cytostatic and immunosuppressive drugs, glucocorticosteroids (with systemic use) and procainamide

Concomitant use with ACE inhibitors may increase the risk of leukopenia.

Preparations for general anesthesia

Concomitant use of ACE inhibitors and general anaesthetics may lead to an increased antihypertensive effect.

Gold preparations

When using ACE inhibitors, including perindopril, in patients receiving intravenous gold preparation (sodium aurothiomalate), a symptom complex was described, including facial skin hyperemia, nausea, vomiting, and hypotension.

Co-trimoxazole (sulfamethoxazole + trimethoprim)

Concomitant use with ACE inhibitors may increase the risk of hyperkalemia.

Gliptins (linagliptin, saxagliptin, sitagliptin, vildagliptin)

Concomitant use with ACE inhibitors may increase the risk of angioedema due to suppression of dipeptidyl peptidase IV (DPP-IV) activity by gliptin.

Sympathomimetics

Sympathomimetics may weaken the antihypertensive effect of ACE inhibitors.

Concomitant use with ACE inhibitors may increase the risk of hyperkalemia. It is recommended to monitor the potassium content in the blood serum.

Heparin

Concomitant use with ACE inhibitors may increase the risk of hyperkalemia. It is recommended to monitor the potassium content in the blood serum.

Tissue plasminogen activators

Observational studies have revealed an increased incidence of angioedema in patients taking ACE inhibitors after the use of alteplase for thrombolytic therapy of ischemic stroke.

Ko-Dalneva®

Simultaneous use that requires special attention

Baclofen

It is possible to increase the antihypertensive effect. Blood pressure and renal function should be monitored, and if necessary, the dose of antihypertensive drugs should be adjusted.

Simultaneous use that requires attention

Antihypertensive agents (e. g. beta-blockers) and vasodilators

When used concomitantly with antihypertensive drugs, it is possible to increase the antihypertensive effect. Caution should be exercised when used concomitantly with nitroglycerin, other nitrates or other vasodilators, as this may lead to an additional decrease in blood pressure.

Corticosteroids (mineral and glucocorticosteroids), tetracosactide (systemic action)

Reduced antihypertensive effect (fluid and sodium retention as a result of corticosteroids).

Alpha-blockers (prazosin, alfuzosin, doxazosin, tamsulosin, terazosin)

Increased antihypertensive effect and increased risk of orthostatic hypotension.

Amifostin

The antihypertensive effect of amlodipine may be enhanced.

Tricyclic Antidepressants/Antipsychotics/General Anaesthetics

Increased antihypertensive effect and increased risk of orthostatic hypotension (additive effect).

How to take, course of use and dosage

Inside,1 tablet 1 time a day, preferably in the morning, before meals.

The dose of Ko-Dalneva® is selected after previously titrated doses of individual active components of the drug.

The maximum daily dose of Ko-Dalneva® is 10 mg of amlodipine + 2.5 mg of indapamide + 8 mg of perindopril.

Elderly patients and patients with impaired renal function

Ko-Dalneva® is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 ml / min) (see section “Contraindications”). Ko-Dalneva® can be used in patients with moderate renal impairment (creatinine clearance 30-60 ml / min). Individual selection of amlodipine, indapamide, and perindopril doses is recommended for such patients.

For patients with impaired renal function (creatinine clearance is 60 ml / min or more) no dose adjustment is required. Amlodipine, used in equivalent doses, is equally well tolerated in elderly and younger patients. There is no need to change the dosage regimen in elderly patients, but increasing the dose should be carried out with caution, due to age-related changes and prolongation of T_1/2. Changes in the concentration of amlodipine in blood plasma do not correlate with the severity of renal failure. Amlodipine is not dialyzed.

The elimination of perindoprilat in elderly patients and patients with renal insufficiency is slowed down. Therefore, in such patients, it is necessary to regularly monitor the concentration of creatinine and potassium in the blood plasma.

Patients with impaired liver function

Ko-Dalneva® is contraindicated in patients with severe hepatic insufficiency (see section “Contraindications”).

Caution should be exercised when using the drug in patients with mild to moderate hepatic impairment.

Overdose

Symptoms

The most likely symptoms of overdose are a marked decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (the risk of developing severe and persistent hypotension, including shock and death). Sometimes a pronounced decrease in blood pressure is accompanied by nausea, vomiting, convulsions, dizziness, drowsiness, confusion, oliguria, which can turn into anuria (as a result of hypovolemia). There may also be violations of the water-electrolyte balance (hyponatremia, hypokalemia).

Treatment

Emergency measures are aimed at removing the drug from the gastrointestinal tract: gastric lavage and / or taking activated charcoal, followed by restoring the water-electrolyte balance. With a marked decrease in blood pressure, the patient should be placed with an elevated position of the lower extremities, if necessary, correction of hypovolemia (for example, an intravenous infusion of 0.9% sodium chloride solution).

Perindoprilat, the active metabolite of perindopril, is removed by hemodialysis. Amlodipine binds closely to plasma proteins, so hemodialysis is ineffective.

Indapamide is not removed by hemodialysis.

Description

Tablets 5 mg + 0.625 mg + 2 mg:

Oval, biconvex tablets of white or almost white color, with a risk on one side.

Tablets 5 mg + 1.25 mg + 4 mg:

Round, slightly biconvex tablets of white or almost white color, with a chamfer on both sides.

Tablets 5 mg + 2.5 mg + 8 mg:

Round, biconvex tablets of white or almost white color, with a chamfer on both sides.

Tablets 10 mg + 1.25 mg + 4 mg:

Oval, biconvex tablets of white or almost white color, with a risk on one side.

Tablets 10 mg + 2.5 mg + 8 mg:

Round, biconvex tablets of white or almost white color, with a chamfer on both sides and a risk on one side.

Special instructions

Hepatic insufficiency mild and moderate severity, renal failure of moderate severity (CC 30-60 ml/min), systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), bilateral renal artery stenosis, stenosis of the artery to a solitary kidney, therapy with immunosuppressants, with allopurinol, procainamide by the (risk of neutropenia and agranulocytosis), the simultaneous use with drugs that can cause polymorphic ventricular tachycardia type “pirouette”, the simultaneous use of potassium-sparing diuretics, potassium and lithium, the simultaneous use of drugs that lengthen the QT interval, hyperkalemia, the oppression of bone marrow hematopoiesis, decreased blood volume (diuretics, diet with restriction of salt, vomiting, diarrhea, hemodialysis), coronary heart disease (CHD), unstable angina (with the exception of prinzmetals angina pectoris), atherosclerosis, cerebrovascular disease, renovascular hypertension, diabetes, CHF (III-IV functional class NYHA classification), acute myocardial infarction (within 1 month after myocardial infarction), a syndrome of weakness of the sinus node, disruption of water and electrolyte balance, the use in patients with prolonged QT interval on the electrocardiogram (ECG), hyperuricemia (especially in combination with gout and urate nephrolithiasis by), hyperparathyroidism, the simultaneous use of dantrolene, estramustine, the simultaneous use with inducers and/or inhibitors of CYP3A4, surgery/General anesthesia, labile blood pressure, a kidney dialysis using high-flow membranes (e. g., AN69®), before treatment, apheresis of low-density lipoprotein (LDL) with dextran sulfate, simultaneous desensitizing therapies allergens (e. g. Hymenoptera venom), condition after kidney transplantation, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy (HACMP), congenital deficiency of glucose-6-phosphate dehydrogenase, use in elderly patients and in patients of the Negroid race.

Contraindicated in persons under 18 years of age (efficacy and safety have not been established).

Elderly patients and patients with impaired renal function

Ko-Dalneva® is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 ml / min) (see section “Contraindications”). Ko-Dalneva® can be used in patients with moderate renal impairment (creatinine clearance 30-60 ml / min). Individual selection of amlodipine, indapamide, and perindopril doses is recommended for such patients.

For patients with impaired renal function (creatinine clearance is 60 ml / min or more) no dose adjustment is required. Amlodipine, used in equivalent doses, is equally well tolerated in elderly and younger patients. There is no need to change the dosage regimen in elderly patients, but increasing the dose should be carried out with caution, due to age-related changes and prolongation of T_1/2. Changes in the concentration of amlodipine in blood plasma do not correlate with the severity of renal failure. Amlodipine is not dialyzed.

The elimination of perindoprilat in elderly patients and patients with renal insufficiency is slowed down. Therefore, in such patients, it is necessary to regularly monitor the concentration of creatinine and potassium in the blood plasma.

Patients with impaired liver function

Ko-Dalneva® is contraindicated in patients with severe hepatic insufficiency (see section “Contraindications”).

Caution should be exercised when using the drug in patients with mild to moderate hepatic impairment.

Ko-Dalneva®

Impaired renal function

Ko-Dalneva® is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 ml / min).

Ko-Dalneva® can be used in patients with moderate renal impairment (creatinine clearance 30-60 ml / min). Individual selection of amlodipine, indapamide, and perindopril doses is recommended for such patients.

Some patients with hypertension without previous apparent renal impairment may develop laboratory signs of functional renal failure during therapy. In this case, treatment with the drug should be discontinued. In the future, you can resume combination therapy using a low-dose combination of perindopril and indapamide, or use these drugs separately. These patients need regular monitoring of their serum potassium and creatinine levels 2 weeks after the start of therapy and every 2 months thereafter.

In patients with bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney during therapy with ACE inhibitors, an increase in serum urea and creatinine concentrations may occur, usually with discontinuation of therapy.

The development of renal failure is more common in patients with severe CHF or initial renal dysfunction, including renal artery stenosis.

Arterial hypotension and impaired water-electrolyte balance

Patients with hyponatremia (especially with renal artery stenosis, including bilateral) are at risk of sudden hypotension. Therefore, you should pay attention to possible symptoms of dehydration and a decrease in the content of electrolytes in the blood plasma, for example, after diarrhea or vomiting. The use of ACE inhibitors causes blockade of the RAAS, and therefore may be accompanied by a sharp decrease in blood pressure and / or an increase in the concentration of creatinine in blood plasma, which indicates the development of functional renal failure. These phenomena are more often observed with the first dose of the drug or during the first two weeks of therapy and sometimes develop acutely. Such patients need regular monitoring of blood plasma electrolyte levels. Severe hypotension may require intravenous use of 0.9% sodium chloride solution. Transient arterial hypotension is not a contraindication for continuing therapy. After recovery of circulating blood volume (BCC) and blood pressure, treatment can be resumed using low doses of perindopril and indapamide, or used separately.

Elderly patients

Before starting taking Ko-Dalneva®, it is necessary to evaluate the functional activity of the kidneys and the content of potassium in the blood plasma. At the beginning of therapy, the dose of the drug is selected taking into account the degree of reduction in blood pressure, especially in the case of a decrease in BCC and loss of electrolytes, which avoids a sharp decrease in blood pressure.

Atherosclerosis

The risk of hypotension exists in all patients, but special care should be taken in patients with CHD and cerebrovascular diseases. In such patients, treatment begins with low doses of the drug.

Children

Ko-Dalneva® is contraindicated in children under 18 years of age due to the lack of data on efficacy and safety in this age group.

Amlodipine

During treatment with amlodipine, it is necessary to monitor body weight and sodium intake, and prescribe an appropriate diet. It is necessary to maintain dental hygiene and follow up with a dentist (to prevent soreness, bleeding and gum hyperplasia).

Patients with low body weight, short stature, and severe hepatic impairment may require a lower dose.

CHF

In patients with CHF (NYHA functional class III and IV), treatment is carried out with caution, due to the possibility of developing pulmonary edema. BMCC, including amlodipine, should be used with caution in patients with CHF, due to the possible increase in the risk of adverse events from the cardiovascular system and mortality.

Impaired liver function

In patients with impaired liver function, T_1/2 and AUC of amlodipine are increased. Amlodipine should be started at the lowest possible dose and caution should be exercised both at the beginning of therapy and when increasing the dose of amlodipine. In patients with severe hepatic impairment, the dose should be increased gradually, and careful monitoring of the clinical condition is necessary.

Elderly patients

In elderly patients, T_{1/2 may increase} and clearance of amlodipine may decrease. No dose adjustment is required, but patients should be carefully monitored.

Indapamide

In the presence of impaired liver function, taking thiazide and thiazide-like diuretics can lead to the development of hepatic encephalopathy. In this case, you should immediately stop taking the drug.

Photosensitivity

Photosensitivity reactions have been reported with thiazide and thiazide-like diuretics. If a photosensitivity reaction develops, treatment should be discontinued. If it is necessary to continue diuretic therapy, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays.

Water-electrolyte balance

Blood plasma sodium content

Before starting treatment, it is necessary to determine the sodium content in the blood plasma. While taking the drug, this indicator should be regularly monitored. All diuretics can cause hyponatremia, which sometimes leads to serious complications. At the initial stage of therapy, a decrease in the sodium content in blood plasma may be asymptomatic, so regular laboratory monitoring is necessary. Elderly patients should be monitored more frequently for sodium levels in the blood plasma.

Hyponatremia combined with hypovolemia can cause dehydration and orthostatic hypotension.

Concomitant reduction of the chlorine content in blood plasma can lead to secondary compensatory metabolic alkalosis (the frequency and severity of this effect are insignificant).

Potassium content in blood plasma

Therapy with thiazide and thiazide-like diuretics is associated with the risk of hypokalemia. Hypokalemia (less than 3.4 mmol) should be avoided. /k) in the following categories of patients from high-risk groups: elderly patients, emaciated patients, patients with cirrhosis of the liver, including edema and ascites, patients with CHD, CHF. In such patients, hypokalemia increases the toxic effect of cardiac glycosides and increases the risk of arrhythmia.

The increased risk group also includes patients with an extended QT interval, both hereditary and caused by drug exposure. Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, especially polymorphic ventricular tachycardia of the “pirouette” type, which can lead to death. In all the cases described above, regular monitoring of the potassium content in the blood plasma is necessary. It is necessary to determine the potassium content in the blood plasma during the first week after the start of therapy. If hypokalemia is detected, appropriate therapy should be performed.

Blood plasma calcium content

Thiazide and thiazide-like diuretics reduce the excretion of calcium by the kidneys, which may cause a slight temporary increase in the content of calcium in the blood plasma. Severe hypercalcemia may be associated with previously undiagnosed hyperparathyroidism. In such cases, it is necessary to conduct a study of the function of the parathyroid glands, first canceling the use of diuretics.

Uric acid

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

Impaired renal function

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

In patients with hypovolemia and hyponatremia, a temporary decrease in GFR and an increase in urea and creatinine concentrations in blood plasma can be observed at the beginning of diuretic therapy. This transient functional renal insufficiency is not dangerous for patients with unchanged renal function, but its severity may increase in patients with renal insufficiency.

In such patients, the potassium and creatinine levels in the blood plasma should be regularly monitored.

Athletes

Indapamide can give a positive reaction during doping control.

Acute myopia and secondary acute angle-closure glaucoma

Sulfonamides and their derivatives can cause an idiosyncratic reaction, leading to the development of acute transient myopia and an acute attack of angle-closure glaucoma. If left untreated, an acute attack of angle-closure glaucoma can lead to permanent vision loss. First of all, it is necessary to stop taking the drug as soon as possible. If intraocular pressure remains uncontrolled, urgent medical treatment or surgery may be required. Risk factors for developing an acute attack of angle-closure glaucoma include a history of allergic reactions to sulfonamide derivatives and penicillins.

Perindopril

Double blockade of the RAAS

There is evidence of an increased risk of hypotension, hyperkalemia, and impaired renal function (including acute renal failure) with concomitant use of ACE inhibitors and ARA II or aliskiren. Therefore, double blockade of the RAAS by combining an ACE inhibitor with ARA II or aliskiren is not recommended (see the section “Interaction with other drugs”). If a double blockade is necessary, it should be performed under the strict supervision of a specialist with regular monitoring of kidney function, blood plasma potassium and blood pressure.

Concomitant use of ACE inhibitors with aliskiren or drugs containing aliskiren is contraindicated in patients with DM and/or moderate to severe renal impairment (GFR less than 60 ml/min / 1.73 m2 of body surface area) and is not recommended in other patients.

Concomitant use of ACE inhibitors with ARA II is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

Neutropenia/Agranulocytosis/Thrombocytopenia/Anemia

Neutropenia/agranulocytosis, thrombocytopenia, and anemia may occur while taking ACE inhibitors. Neutropenia is rare in patients with normal renal function in the absence of other risk factors. After discontinuation of the ACE inhibitor, neutropenia and agranulocytosis resolve independently. Perindopril should be used with extreme caution in patients with systemic connective tissue diseases treated with immunosuppressants, allopurinol or procainamide, especially in patients with impaired renal function. Some patients developed severe infections, in some cases resistant to intensive antibiotic therapy. When using perindopril in such patients, it is recommended to periodically monitor the number of white blood cells in the blood plasma. If you experience any symptoms of infectious diseases (for example, sore throat, fever), patients should consult a doctor.

Hypersensitivity/angioedema

Angioedema of the face, extremities, lips, tongue, vocal folds and/or larynx may develop in rare cases while taking ACE inhibitors, including perindopril. If symptoms appear, you should immediately stop taking the drug and continue monitoring the patient until the symptoms are completely relieved. As a rule, swelling of the face and lips does not require treatment, although antihistamines can be used to relieve symptoms.

Angioedema accompanied by laryngeal edema can be fatal. Swelling of the tongue, vocal folds, or larynx can lead to airway obstruction. If such symptoms occur, immediately enter subcutaneously a solution of epinephrine (epinephrine) in a dilution of 1:1000 (0.3-0.5 ml) and / or ensure patency of the respiratory tract. Patients with a history of angioedema that is not associated with ACE inhibitors may have an increased risk of developing angioedema when taking this group of drugs.

In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. At the same time, patients complain of abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and with normal levels of C1-esterase. The diagnosis was established using computed tomography, ultrasound examination of the abdominal organs, or during surgery.Symptoms disappear after discontinuation of ACE inhibitors. Therefore, in patients with complaints of abdominal pain taking ACE inhibitors, the differential diagnosis should take into account the possibility of developing angioedema of the intestine.

mTOR inhibitors

In patients taking concomitant mTOR inhibitors (e. g., sirolimus, everolimus, temsirolimus), therapy may be associated with an increased risk of angioedema (e. g., upper respiratory tract or tongue edema with / without respiratory disorders).

Anaphylactoid reactions during desensitization

There are isolated reports of anaphylactoid reactions in patients taking ACE inhibitors during desensitizing therapy (for example, hymenopteran venom: bees, wasps). The development of such reactions was avoided by temporarily stopping ACE inhibitors (at least 24 hours before desensitization), with accidental use of an ACE inhibitor, the anaphylactoid reaction occurred again.

Anaphylactoid reactions during LDL apheresis

In rare cases, patients receiving ACE inhibitors may develop life-threatening anaphylactoid reactions during LDL apheresis using dextran sulfate. To prevent such reactions, you should temporarily stop taking ACE inhibitors before each apheresis procedure.

Hemodialysis

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

Primary hyperaldosteronism

Patients with primary hyperaldosteronism are generally immune to antihypertensive drugs that are based on RAAS inhibition. Therefore, the use of this drug is not recommended.

Cough

During ACE inhibitor therapy, a dry cough may occur. Cough persists for a long time against the background of taking drugs of this group and disappears after their cancellation. If a patient has a dry cough, you should be aware of the possibility of its occurrence in connection with taking an ACE inhibitor. If it is necessary to use drugs of this group, the use of an ACE inhibitor can be continued.

Aortic and mitral stenosis, HOCMP

ACE inhibitors should be used with caution in patients with left ventricular outflow tract obstruction and mitral stenosis.

Withacharnydiabetes

In patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, regular monitoring of plasma glucose concentrations is necessary during the first month of treatment with an ACE inhibitor.

Surgical intervention/General anesthesia

The use of ACE inhibitors in patients undergoing surgery with general anesthesia may lead to a pronounced decrease in blood pressure, especially when using general anesthesia agents that have an antihypertensive effect. It is recommended to stop taking long-acting ACE inhibitors, including perindopril,24 hours before surgery.

Ethnic differences

Patients of the black race are more likely than those of other races to develop angioedema due to the use of ACE inhibitors. Perindopril, like other ACE inhibitors, apparently has 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 black race often have low plasma renin activity.

Liver failure

In rare cases, cholestatic jaundice occurs while taking ACE inhibitors. With the progression of this syndrome, fulminant liver necrosis develops, sometimes with a fatal outcome. The mechanism of development of this syndrome is unclear. If there is a significant increase in the activity of “liver” enzymes or jaundice occurs while taking ACE inhibitors, the drug should be discontinued and the patient should continue to be monitored.

Hyperkalemia

The use of ACE inhibitors can cause hyperkalemia due to inhibition of aldosterone release, usually insignificant in patients with normal renal function. Risk factors for hyperkalemia include renal failure, advanced age (over 70 years), diabetes mellitus, certain concomitant conditions (dehydration, acute decompensation of chronic heart failure, metabolic acidosis), concomitant use of potassium-sparing diuretics (spironolactone, eplerenone, triamterene, amiloride), potassium preparations, potassium-containing salt substitutes, and other agents that increase the potassium content in blood plasma (for example, heparin trimethoprim or co-trimoxazole (sulfamethoxazole + trimethoprim) and especially aldosterone or ARA II antagonists, ASA ≥ 3 g/day, COX-2 inhibitors and non-selective NSAIDs, immunosuppressants such as cyclosporine or tacrolimus (especially in patients with reduced renal function). Hyperkalemia can lead to serious, sometimes fatal cardiac arrhythmias. Caution should be exercised when concomitantly using ACE inhibitors and potassium-sparing diuretics and ARA II, it is necessary to monitor renal function and serum potassium.

Kidney transplantation

There is no experience of using perindopril in patients with a recent kidney transplant.

Renovascular hypertension

The method of treating renovascular hypertension is revascularization. However, the use of ACE inhibitors can be effective in patients with renovascular hypertension, both waiting for surgery and when it is impossible to perform it.

Patients with bilateral renal artery stenosis or stenosis of the renal artery of the only functioning kidney on the background of ACE inhibitor therapy increase the risk of hypotension and renal failure. Taking diuretics may be an additional risk factor. Deterioration of renal function can be observed even with a slight change in the concentration of creatinine in blood plasma, even in patients with unilateral renal artery stenosis.

In patients with diagnosed or suspected renal artery stenosis, treatment should be initiated with lower doses of Ko-Dalneva®. Some patients may develop functional renal failure, which resolves after discontinuation of the drug.

Due to the possibility of weakness and dizziness associated with the use of Ko-Dalneva®, care should be taken when driving vehicles and working with other technical devices that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Tablets,5 mg + 0.625 mg + 2 mg,5 mg + 1.25 mg + 4 mg,5 mg + 2.5 mg + 8 mg,10 mg + 1.25 mg + 4 mg,10 mg + 2.5 mg + 8 mg.

10 or 14 tablets in a contour cell package made of a combined OPA/Al/PVC material and aluminum foil.

1,2,3,6,9 contour cell packages (10 tablets each) or 1,2,4,6 contour cell packages (14 tablets each) together with the instructions for use are placed in a cardboard pack.

Storage conditions

At a temperature not exceeding 25 ° C, in the original packaging.

Keep out of reach of children.

Shelf

life is 2 years.

Do not use the drug after the expiration date.

Active ingredient

Amlodipine, Indapamide, Perindopril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets