CO-DALNEVA PILLS 5MG + 1.25MG + 4MG

Co-Dalneva tablet

1 pill 5 mg + 0.625 mg + 2 mg contains:

Active ingredients:

Amlodipine besylate (amlodipine besylate) 6.935 mg, which is equivalent to Amlodipine 5 mg Indapamide 0.625 mg

Perindopril erbumin B substance-granules 10,206 mg

[The active substance of the substance-granules: Perindopril erbumin 2,000 mg

1 pill 5 mg + 1.25 mg + 4 mg contains:

Active ingredients:

Amlodipine besylate (amlodipine besylate) 6.935 mg, equivalent to amlodipine 5 mg Indapamide 1.250 mg

Perindopril erbumin B substance-granules 20.412 mg

[The active substance of the substance-granules: perindopril erbumin 4,000 mg

1 pill 10 mg + 1.25 mg + 4 mg contains:

Active ingredients:

Amlodipine besylate (amlodipine besylate) 13.870 mg, equivalent to amlodipine 10 mg

Indapamide 1,250 mg

Perindopril erbumin B substance-granules 20.412 mg

[The active substance of the substance-granules: perindopril erbumin 4,000 mg

1 pill 5 mg + 2.5 mg + 8 mg contains:

Active ingredients:

Amlodipine besylate (amlodipine besylate) 6.935 mg, equivalent to amlodipine 5 mg Indapamide 2,500 mg

Perindopril erbumin B substance-granules 40,824 mg

[The active substance of the substance-granules: perindopril erbumin 8,000 mg

1 pill 10 mg + 2.5 mg + 8 mg contains:

Active ingredients:

Amlodipine besylate (amlodipine besylate) 13.870 mg, equivalent to amlodipine 10 mg

Indapamide 2,500 mg

Perindopril erbumin B substance-granules 40,824 mg

[The active substance of the substance-granules: perindopril erbumin 8,000 mg

Therapeutic indications

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

Dosage and administration

Inside, on 1 pill once a day, preferably in the morning, before meals.

The dose of Ko-Dalneva® is selected after a previous titration of doses of individual active ingredients of the drug.

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

Elderly patients and patients with impaired renal function

Co-Dalneva® is contraindicated for use in patients with severe renal dysfunction (CC less than 30 ml / min) (see section “Contraindications”). Co-Dalneva® can be used in patients with moderate renal dysfunction (CC 30-60 ml / min). Such patients are recommended individual selection of doses of amlodipine, indapamide, perindopril.

For patients with impaired renal function (CC is 60 ml / min or more) dose adjustment is not required. Amlodipine, used in equivalent doses, is equally well tolerated by patients of both elderly and younger age. It is not necessary to change the dosing regimen in elderly patients, but the dose should be increased with caution, which is associated with age-related changes and T1 / 2 lengthening.Changes in the concentration of amlodipine in the 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 slow. Therefore, in such patients it is necessary to regularly monitor the concentration of creatinine and the content of potassium in the blood plasma.

Patients with impaired liver function

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

Caution must be exercised when using the drug in patients with mild and moderate liver dysfunction.

Contraindications

• Hypersensitivity to amlodipine and other dihydropyridine derivatives, indapamide and other sulfonamide derivatives, perindopril and other ACE inhibitors, as well as to the excipients that make up the drug.
• Angioedema (angioedema) in history, associated with taking ACE inhibitors.
• Hereditary / idiopathic angioedema.
• Severe arterial hypotension (systolic blood pressure less than 90 mm Hg. Art.).
• Shock, including cardiogenic shock.
• Obstruction of the output tract of the left ventricle (for example, clinically significant aortic stenosis).
• Hemodynamically unstable heart failure after acute myocardial infarction.
• Severe renal failure (CC less than 30 ml / min).
• Severe hepatic impairment, including hepatic encephalopathy.
• Refractory hypokalemia.
• Simultaneous use with aliskiren or drugs containing aliskiren in patients with diabetes and / or moderate or severe renal impairment (glomerular filtration rate (GFR) of less than 60 ml / min / 1.73 m2 of body surface area).
• Concurrent use with angiotensin II receptor antagonists (ARA II) in patients with diabetic nephropathy.
• Pregnancy and breastfeeding period (see section “Use during pregnancy and during breastfeeding”).
• Age up to 18 years (efficacy and safety have not been established).

Given the lack of sufficient clinical experience, should not be used in patients on hemodialysis, as well as in patients with untreated heart failure in the stage of decompensation.

Carefully

Hepatic failure mild to moderate severity, moderately severe renal failure (CC 30-60 ml / min), systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), bilateral renal artery stenosis, single kidney stenosis, immunosuppressant therapy, Allopurinol, procainamide (risk of developing neutropenia and agranulocytosis), simultaneous use with drugs that can cause polymorphic ventricular tachycardia such as "pirouette",simultaneous use with potassium-sparing diuretics, potassium and lithium preparations, simultaneous use of drugs extending the QT interval, hyperkalemia, suppression of bone marrow hematopoiesis, reduced volume of circulating blood unstable angina (with the exception of Prinzmetal stenocardia), atherosclerosis, cerebrovascular diseases, renovascular hypertension, diabetes mellitus, chronic heart failure tolerance (III-IV functional class according to the NYHA classification), acute myocardial infarction (within 1 month after myocardial infarction), sick sinus syndrome combination with gout and urate nephrolithiasis), hyperparathyroidism, simultaneous use of dantrolen, estramustine, simultaneous use with inducers and / or inhibitors of the isoenzyme CYP3A4, surgery / general anesthesia, blood lability, check hemodialysis using high-flow membranes (for example, AN69®), before the procedure of low density lipoprotein apheresis (LDL) using dextran sulfate, simultaneous desensitization therapy with allergens (eg, hymenoptera), a condition after kidney transplantation, aortic stenosis, mitral stenosis,hypertrophic obstructive cardiomyopathy (GOKMP), congenital deficiency of glucose-6-phosphate dehydrogenase, use in elderly patients and in patients of the Negroid race.

Special instructions and precautionary measures

Co-Dalneva®

Renal dysfunction

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

Co-Dalneva® can be used in patients with moderate renal dysfunction (CC 30-60 ml / min). Such patients are recommended individual selection of doses of amlodipine, indapamide, perindopril.

In some patients with hypertension without previous obvious renal dysfunction during therapy, laboratory signs of functional renal failure may appear. In this case, drug treatment should be discontinued. In the future, you can resume combination therapy using low doses of a combination of perindopril and indapamide, or use these drugs separately. Such patients require regular monitoring of the potassium content and serum creatinine concentration 2 weeks after the start of therapy and every 2 months thereafter.

In patients with bilateral renal artery stenosis or arterial stenosis of the only functioning kidney during therapy with ACE inhibitors, it is possible to increase the concentration of urea and creatinine in the blood serum, usually taking place when therapy is canceled.

The development of renal failure occurs more often in patients with severe CHF or an initial impairment of renal function, including renal artery stenosis.

Hypotension and impaired water-electrolyte balance

Patients with hyponatremia (especially with renal artery stenosis, including bilateral) have a risk of sudden development of arterial hypotension. Therefore, one should pay attention to possible symptoms of dehydration and reduction of electrolytes in the blood plasma, for example, after diarrhea or vomiting. The use of ACE inhibitors causes a blockage of the RAAS and therefore may be accompanied by a sharp decrease in blood pressure and / or an increase in plasma creatinine, which indicates the development of functional renal failure. These phenomena are more often observed when taking the first dose of the drug or during the first two weeks of therapy and sometimes develop acutely. Such patients require regular monitoring of the plasma electrolyte content. In severe hypotension, intravenous administration of 0.9% sodium chloride solution may be required. Transient arterial hypotension is not a contraindication for continued therapy. After the restoration 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 you start taking Co-Dalnev®, 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 decrease in blood pressure, especially in the case of a decrease in BCC and loss of electrolytes, thus avoiding a sharp decrease in blood pressure.

Atherosclerosis

The risk of developing hypotension exists in all patients, however, special care should be taken in patients with coronary heart disease (CHD) and cerebrovascular diseases. In these patients, treatment begins with low doses of the drug.

Children

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

Amlodipine

During the period of treatment with amlodipine, it is necessary to control body weight and sodium intake, the appointment of an appropriate diet. It is necessary to maintain dental hygiene and observation at the dentist (to prevent pain, bleeding and gum hyperplasia).

Patients with low body mass, patients of short stature and patients with severe liver dysfunction may require a lower dose.

CHF

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

Liver dysfunction

In patients with impaired liver function T1/2 and amlodipine AUC increases. Reception of an amlodipin should be begun with the lowest doses and to be careful both at the beginning of therapy, and at an increase in a dose of an amlodipin.Patients with severe impaired liver function should be gradually increased, careful monitoring of the clinical condition is necessary.

Elderly patients

Elderly patients may increase T1/2 and decrease clearance of amlodipine. Dose adjustment is not required, but careful monitoring of patients is necessary.

Indapamide

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

Photosensitivity

While receiving thiazide and thiazide-like diuretics, photosensitivity reactions have been reported. In the event of a photosensitivity reaction, treatment should be discontinued. If you need to continue diuretic therapy, it is recommended to protect the skin from exposure to sunlight or artificial UV rays.

Water and electrolyte balance

Sodium content in blood plasma

Prior to 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 sodium content in the blood plasma may be asymptomatic, therefore regular laboratory monitoring is necessary.Elderly patients show more frequent monitoring of sodium in plasma.

The content of potassium in the blood plasma

Therapy with thiazide and thiazide-like diuretics is associated with the risk of hypokalemia. It is necessary to avoid hypokalemia (less than 3.4 mmol / l) in the following categories of patients from high-risk groups: elderly patients, exhausted patients, patients with cirrhosis of the liver, including edema and ascites, patients with coronary artery disease, heart failure. In such patients, hypokalemia increases the toxic effect of cardiac glycosides and increases the risk of developing arrhythmias.

Patients with a prolonged QT interval, both hereditary and drug-induced, are also at increased risk. Hypokalemia, like bradycardia, contributes to the development of severe heart rhythm disturbances, especially polymorphic ventricular tachycardia of the “pirouette” type, which can be fatal. In all the cases described above, regular monitoring of potassium in the blood plasma is necessary. It is necessary to determine the content of potassium in the blood plasma during the first week after the start of therapy. If hypokalemia is detected, appropriate therapy should be carried out.

Plasma Calcium

Thiazide and thiazide-like diuretics reduce the excretion of calcium by the kidneys, which can cause a slight temporary increase in plasma calcium levels. 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, by abolishing diuretic drugs.

Uric acid

In patients with an increased concentration of uric acid in the blood plasma during therapy, the incidence of gout attacks may increase.

Renal dysfunction

Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (plasma creatinine concentration in adult patients below 25 mg / l or 220 μmol / l). In elderly patients, QC is calculated taking into account age, body weight and gender.

In patients with hypovolemia and hyponatremia, at the beginning of diuretic therapy, there may be a temporary decrease in the glomerular filtration rate and an increase in the concentration of urea and creatinine in the blood plasma. This transient functional renal failure is not dangerous for patients with unchanged kidney function, but in patients with renal insufficiency, its severity may increase.

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

Athletes

Indapamide can give a positive reaction during doping control.

Perindopril

Double blockade of RAAS

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

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

The simultaneous 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 can occur while taking ACE inhibitors. In patients with normal renal function in the absence of other risk factors, neutropenia rarely develops. After discontinuation of the ACE inhibitor, neutropenia and agranulocytosis pass independently. With particular caution should be used perindopril in patients with systemic connective tissue diseases during therapy 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 these patients, it is recommended to periodically monitor the number of leukocytes in the blood plasma. If any symptoms of an infectious disease (eg, sore throat, fever) appear, patients should consult a doctor.

Hypersensitivity / Angioedema

While taking ACE inhibitors, including perindopril, in rare cases, the development of angioedema of the face, extremities, lips, tongue, vocal folds and / or larynx may be observed. If symptoms occur, stop taking the drug immediately 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 may be used to relieve symptoms.

Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, vocal cords or larynx can lead to airway obstruction. If these symptoms appear, a solution of epinephrine (adrenaline) should be immediately administered subcutaneously at a dilution of 1: 1000 (0.3-0.5 ml) and / or the airway should be 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 complaints of 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 C1-esterase. The diagnosis was established using computed tomography, ultrasound of the abdominal organs or during surgery. Symptoms disappear after discontinuation of ACE inhibitors. Therefore, in patients with complaints of pain in the abdomen, taking ACE inhibitors, when conducting differential diagnosis, it is necessary to consider the possibility of the development of angioedema.

MTOR inhibitors

In patients who are simultaneously taking mTOR inhibitors (for example, sirolimus, everolimus, temsirolimus), therapy may be associated with an increased risk of developing angioedema (for example, swelling of the upper respiratory tract or tongue with / without respiratory disorders).

Anaphylactoid reactions during desensitization

There are separate reports on the development of anaphylactoid reactions in patients who took ACE inhibitors during desensitization therapy (for example, hymenoptera poison: bees, wasps). The development of such reactions was avoided by the temporary cancellation of ACE inhibitors (no less than 24 hours before desensitization), with the accidental use of an ACE inhibitor anaphylactoid reaction occurred again.

Anaphylactoid reactions during LDL apheresis

In rare cases, life-threatening anaphylactoid reactions may develop in patients receiving an ACE inhibitor while performing an apheresis of LDL 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 during hemodialysis using high-flow membranes (for example, AN69®) Anaphylactoid reactions developed. Therefore, it is recommended to use a membrane of a different type or use an antihypertensive drug