Co-Dalneva Tablets, 30 pcs., 5+0.625 + 2 mg + mg + mg

Pharmacodynamics and pharmacokinetics

Pharmacodynamics

Antihypertensive drug with a combined composition of active ingredients.

Perindopril is an active ACE inhibitor that transforms angiotensin I into angiotensin II , which has a pronounced vasoconstrictor effect. ACE also has a destructive effect on bradykinin , which has a vasodilating effect. ACE inhibition increases the activity of the kallikrein-kinin system .

The pharmacological effect of Perindopril is determined by its active metabolite, perindoprilate , which has a pronounced therapeutic effect in arterial hypertension of any degree, in any body position, reducing systolic and diastolic pressure. blood flow decreases and peripheral blood flow increases, while heart rate remains unchanged.

The hypotensive effect is maximally manifested 4-6 hours after taking perindopril and persists throughout the day. The decrease in blood occurs quickly, and a pronounced therapeutic effect occurs 3-4 weeks after starting the drug and is not accompanied by tachycardia . withdrawal syndrome . In addition to the vasodilator effect. Perindopril reduces left ventricular hypertrophy and restores the elasticity and structure of blood vessels.

Amlodipine dihydropyridine derivative , and has a pronounced hypotensive and antianginal effect. Having a blocking effect, it reduces the process of transition of calcium ions into the cell. The antianginal effect is caused by the dilation of the blood vessels of the heart muscle and peripheral arteries: it reduces afterload on the myocardium, peripheral vascular resistance , myocardial oxygen demand, and relieves spasm of the coronary arteries. In patients with angina pectoris it reduces the severity of ischemia of the heart muscle , reduces the number of angina attacks, increases exercise tolerance, and reduces the need for nitroglycerin .

It has a pronounced dose-dependent hypotensive effect, which is caused by a vasodilating effect on the vascular muscles. Reduces hypertrophy of the left ventricular muscles, while it does not affect the conductivity and contractility of the myocardium, inhibits platelet , does not cause an increase in heart rate , and has a mild natriuretic effect. It does not affect metabolism and the concentration of lipids in the blood and can be prescribed to patients with diabetes , bronchial asthma , and gout . A pronounced therapeutic effect occurs after 6-10 hours and lasts for an average of about a day.

Pharmacokinetics

Perindopril is rapidly absorbed from the gastrointestinal tract after oral administration, while the bioavailability of perindopril with food is reduced. Cmax in the blood is reached within one hour. Low connection with blood proteins (20%). Pharmacological activity is achieved due to the metabolite - perindoprilate . Excreted in urine. T1/2 of perindopril is about one hour.

Amlodipine is well absorbed from the gastrointestinal tract , absolute bioavailability is 80%, food intake has no effect on bioavailability. Cmax in the blood occurs after 8-10 hours. Metabolized in the liver to form metabolites that do not have activity. It is excreted mainly in the urine.

Pharmacological groups

• Antihypertensive combination drug (slow calcium channel blocker + diuretic + angiotensin-converting enzyme inhibitor) [ACE inhibitors in combinations]
• Antihypertensive combination drug (slow calcium channel blocker + diuretic + angiotensin-converting enzyme inhibitor) [Diuretics in combinations]
• Antihypertensive combination drug (slow calcium channel blocker + diuretic + angiotensin-converting enzyme inhibitor) [Calcium channel blockers in combinations]

Contraindications

High sensitivity to the drug, age under 18 years, renal failure , pregnancy , lactation.

Use with caution in patients with CHF immunosuppressant therapy , cardiomyopathy , mitral/aortic stenosis , atherosclerosis , cerebrovascular diseases, hemodialysis , diabetes mellitus , when taking potassium-sparing diuretics , estramustine , dantrolene , lithium drugs, with scleroderma , lupus erythematosus , black patients ide race.

Co-Dalneva tablet 5 mg+2.5 mg+8 mg x30

Co-Dalneva tablet 5 mg+2.5 mg+8 mg x30 ATX code: C09BX01 (Perindopril in combination with amlodipine and indapamide)

Active substances indapamide Rec.INN WHO registered amlodipine Rec.INN WHO registered perindopril Rec.INN WHO registered

Dosage form

KO-DALNEVA® tab. 5 mg+2.5 mg+8 mg: 10, 14, 20, 28, 30, 56, 60, 84 or 90 pcs.

reg. No.: LP-002958 dated 04/16/15 - Valid

Release form, composition and packaging

Tablets are white or almost white, round, biconvex, beveled on both sides.

1 tab. amlodipine besylate 6.935 mg, which corresponds to the content of amlodipine 5 mg indapamide 2.5 mg perindopril erbumine B substance-granules*, 40.824 mg, which corresponds to the content of perindopril erbumine 8 mg

Excipients: microcrystalline cellulose - 165.761 mg, pregelatinized starch - 21 mg, sodium carboxymethyl starch - 8.4 mg, sodium bicarbonate - 0.76 mg, colloidal silicon dioxide - 0.43 mg, magnesium stearate - 1.4 mg.

*Excipients of the granular substance: microcrystalline cellulose 31.6 mg, calcium chloride hexahydrate 2.4 mg.

10 pieces. — cellular contour packages (1) — cardboard packs. 10 pieces. — contour cell packaging (2) — cardboard packs. 10 pieces. — cellular contour packages (3) — cardboard packs. 10 pieces. — contour cell packaging (6) — cardboard packs. 10 pieces. — contour cell packaging (9) — cardboard packs. 14 pcs. — cellular contour packages (1) — cardboard packs. 14 pcs. — contour cell packaging (2) — cardboard packs. 14 pcs. — contour cell packaging (4) — cardboard packs. 14 pcs. — contour cell packaging (6) — cardboard packs.

Clinical and pharmacological group: Antihypertensive drug

Pharmacotherapeutic group: Antihypertensive combined drug (slow calcium channel blocker + diuretic + angiotensin-converting enzyme inhibitor)

pharmachologic effect

Pharmacokinetics

Indications

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

ICD-10 codes

Dosage regimen

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

The dose of Co-Dalneva® is selected after previously titrated doses of the individual active components of the drug. The maximum daily dose of Co-Dalneva® is 10 mg amlodipine + 2.5 indapamide + 8 mg perindopril.

Elderly patients and patients with impaired renal function

The drug Co-Dalneva® is contraindicated for use in patients with moderate and severe renal impairment (creatinine clearance less than 60 ml/min) (see section “Contraindications”). The drug Co-Dalneva® can be used in patients with CC equal to or exceeding 60 ml/min. For such patients, individual selection of doses of amlodipine, indapamide, and perindopril is recommended.

Amlodipine, used in equivalent doses, is equally well tolerated by both elderly and younger patients. There is no need to change the dosage regimen in elderly patients, however, increasing the dose should be done with caution, which is associated with age-related changes and prolongation of T1/2. Changes in the concentration of amlodipine in blood plasma do not correlate with the severity of renal failure.

The elimination of perindoprilate in elderly patients and patients with renal failure is slower. Therefore, in such patients it is necessary to regularly monitor the concentration of creatinine and potassium levels in the blood plasma.

Patients with liver dysfunction

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

Caution should be exercised when using the drug in patients with mild to moderate liver dysfunction.

Side effect

World Health Organization (WHO) classification of the incidence of side effects: very common >1/10, common >1/100 to 1/1000 to 1/10000 to

Contraindications for use

- hypersensitivity to amlodipine and other dihydropridine derivatives, indapamide and other sulfonamide derivatives, perindopril and other ACE inhibitors, as well as to the excipients included in the drug,

- history of angioedema (Quincke's edema) associated with taking ACE inhibitors,

- hereditary/idiopathic angioedema,

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

- severe arterial hypotension (systolic blood pressure less than 90 mm Hg),

- shock, incl. cardiogenic shock,

- unstable angina (with the exception of Prinzmetal's angina),

- obstruction of the left ventricular outflow tract (for example, clinically significant aortic stenosis),

- hemodynamically unstable heart failure after acute myocardial infarction,

- renal failure (creatinine clearance less than 60 ml/min),

- severe liver failure, incl. hepatic encephalopathy,

- refractory hypokalemia,

- simultaneous use with drugs that can cause polymorphic ventricular ari (see section “Interaction with other drugs”),

- simultaneous use with potassium-sparing diuretics, potassium and lithium preparations, in patients with elevated potassium levels in the blood plasma,

- simultaneous use of drugs that prolong the QT interval,

- simultaneous use with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus,

— pregnancy and breastfeeding (see section “Pregnancy and breastfeeding”),

- age under 18 years (efficacy and safety have not been established).

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

With caution (see also sections “Special instructions” and “Interaction with other drugs”): mild to moderate liver failure, systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), immunosuppressant therapy, allopurinol, procainamide (risk of developing neutropenia and agranulocytosis), inhibition of bone marrow hematopoiesis, reduced circulating blood volume (taking diuretics, salt-restricted diet, vomiting, diarrhea, hemodialysis), coronary artery disease, atherosclerosis, cerebrovascular diseases, renovascular hypertension, diabetes mellitus, chronic heart failure (NYHA functional class IV), hyperuricemia (especially in combination with gout and urate nephrolithiasis), simultaneous use of dantrolene, estramustine, surgery/general anesthesia, blood pressure lability, hemodialysis using high-flow membranes (for example, AN69®) , before the procedure of low-density lipoprotein (LDL) apheresis with dextran sulfate, simultaneous desensitization therapy with allergens (for example, Hymenoptera venom), condition after kidney transplantation, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy (HOCM), use in elderly patients and in patients of the Negroid race.

Use during pregnancy and breastfeeding

Pregnancy

Co-Dalneva® is contraindicated during pregnancy (see section “Contraindications”).

If you are planning pregnancy or if it occurs while taking Co-Dalneva®, you should immediately stop taking it and prescribe alternative antihypertensive therapy with a proven safety profile.

The safety of amlodipine during pregnancy has not been established. The limited available data on the use of amlodipine and other BMCCs during pregnancy indicate the absence of negative effects on the fetus. In animal experiments, signs of reproductive toxicity were observed when using high doses of amlodipine. Some patients receiving BMKK therapy experienced a reversible decrease in sperm motility. There is insufficient clinical data regarding the potential effect of amlodipine on reproductive function. Long-term use of thiazide diuretics in the third trimester of pregnancy can cause hypovolemia in the mother and a decrease in uteroplacental blood flow, which leads to fetoplacental ischemia and fetal growth retardation. In rare cases, while taking diuretics shortly before birth, newborns develop hypoglycemia and thrombocytopenia.

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, the effect of ACE inhibitors on the fetus can lead to disruption of its development (decreased renal function, oligohydramnios, delayed ossification of the skull bones) and the development of complications in newborns (renal failure, arterial hypotsia, hyperkalemia). If an ACE inhibitor was used in the second or third trimester of pregnancy, it is recommended to conduct an ultrasound examination of the fetal kidneys and skull bones. Newborns whose mothers received ACE inhibitors during pregnancy require careful medical supervision because there is a risk of developing arterial hypotension.

Breastfeeding period

There is no data on the excretion of amlodipine in breast milk. However, it is known that other BMCCs, dihydropyridine derivatives, are excreted in breast milk. Indapamide is excreted 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. It is unknown whether peripdopril is excreted in breast milk.

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

Use for liver dysfunction

The drug Co-Dalneva® should be used with caution in patients with mild to moderate liver failure.

Use of the drug in patients with severe liver failure, incl. with hepatic encephalopathy is contraindicated.

Use for renal impairment

The drug Co-Dalneva® is contraindicated for use in patients with moderate and severe renal impairment (creatinine clearance less than 60 ml/min). The drug can be used in patients with CC equal to or exceeding 60 ml/min. For such patients, individual selection of doses of amlodipine, indapamide, and perindopril is recommended.

Use in children

The use of the drug in children and adolescents under 18 years of age is contraindicated (efficacy and safety have not been established).

Use in elderly patients

Use the drug with caution in elderly patients.

special instructions

Ko-Dalneva®

Renal dysfunction

Co-Dalneva® is contraindicated in patients with CC less than 60 ml/min. In some patients with hypertension without previous obvious renal impairment, laboratory signs of functional renal failure may appear during therapy. In this case, treatment with the drug should be stopped. In the future, combination therapy can be resumed using low doses of combinations of perindopril and indapamide, or these drugs can be used separately. Such patients require regular monitoring of potassium levels and creatinine concentrations in the blood serum 2 weeks after the start of therapy and every 2 months thereafter.

The development of renal failure more often occurs in patients with severe CHF or initial renal impairment, incl. with renal artery stenosis. The drug is not recommended for use in patients with bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney.

Arterial hypotension and water-electrolyte imbalance

Patients with hyponatremia (especially with renal artery stenosis, including bilateral) are at risk of sudden development of arterial hypotension. Therefore, you should pay attention to possible symptoms of dehydration and decreased electrolyte levels 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 the blood plasma, 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 blood plasma electrolyte levels. In case of severe arterial hypotension, intravenous administration of 0.9% sodium chloride solution may be required. Transient arterial hypotension is not a contraindication for continued therapy. After restoration of blood volume and blood pressure, treatment can be resumed using low doses of perindopril and indapamide, or used separately.

Elderly patients

Before starting to take Co-Dalneva®, it is necessary to evaluate the functional activity of the kidneys and the potassium content 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 blood volume and loss of electrolytes, which helps to avoid a sharp decrease in blood pressure.

Atherosclerosis

The risk of developing arterial hypotension exists in all patients, but special caution should be observed in patients with coronary artery disease and cerebrovascular diseases. In such patients, treatment begins with low doses of the drug.

Amlodipine

CHF

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

Liver dysfunction

In patients with impaired liver function, T1/2 and AUC of amlodipine are increased. Amlodipine should be started with the lowest doses and caution should be exercised both when starting 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 required.

Indapamide

In the presence of liver dysfunction, 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

Cases of photosensitivity reactions have been reported while taking 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 and electrolyte balance

Sodium content in blood plasma

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 sodium levels in the blood plasma may be asymptomatic, so regular laboratory monitoring is necessary. Elderly patients are advised to monitor plasma sodium levels more frequently.

Potassium content in blood plasma

Therapy with thiazide and thiazide-like diuretics is associated with a risk of hypokalemia. Hypokalemia (less than 3.4 mmol/L) should be avoided in the following categories of high-risk patients: elderly patients, malnourished patients, patients with cirrhosis, etc. with edema and ascites, patients with ischemic heart disease, CHF. In such patients, hypokalemia enhances the toxic effect of cardiac glycosides and increases the risk of developing arrhythmia.

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

Calcium content in blood plasma

Thiazide and thiazide-like diuretics reduce the excretion of calcium by the kidneys, which may cause a slight temporary increase in calcium levels 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, having first stopped taking diuretics.

Uric acid

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

Renal dysfunction

Thiazide and thiazide-like diuretics are effective and 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, CC is calculated taking into account age, body weight and gender.

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

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

Athletes

Indapamide may give a positive reaction during doping control.

Peripdopril

Neutropenia/agranulocytosis

While taking ACE inhibitors, neutropenia/agranulocytosis, thrombocytopenia and anemia may occur. 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 resolve on their own. Perindopril should be used with extreme caution 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 such patients, it is recommended to periodically monitor the number of leukocytes in the blood plasma. If any symptoms of infectious diseases appear (for example, sore throat, fever), patients should consult a doctor.

Hypersensitivity/angioedema

While taking ACE inhibitors, incl. and perindopril, in rare cases, the development of angioedema of the face, extremities, lips, tongue, vocal folds and/or larynx may occur. If symptoms appear, you should immediately stop taking the drug and continue to monitor the patient until 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 swelling of the larynx, can be fatal. Swelling of the tongue, vocal folds, or larynx can lead to airway obstruction. If such symptoms appear, you should immediately administer a subcutaneous solution of epinephrine (adrenaline) at a dilution of 1:1000 (0.3-0.5 ml) and/or ensure airway patency. Patients with a history of angioedema not associated with taking ACE inhibitors may have an increased risk of developing it when taking drugs of this group.

In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. In this case, 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 a normal level of C-1 esterase. The diagnosis was made using computed tomography, ultrasound examination of the abdominal organs, or during surgery. Symptoms disappear after stopping ACE inhibitors. Therefore, in patients with complaints of abdominal pain taking ACE inhibitors, when carrying out differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine.

Anaphylactoid reactions during desensitization

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

Anaphylactoid reactions during LDL apheresis

In rare cases, life-threatening anaphylactoid reactions may occur in patients receiving ACE inhibitors during LDL apheresis using dextran sulfate. To prevent such reactions, ACE inhibitors should be temporarily discontinued before each apheresis procedure.

Hemodialysis

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

Cough

During therapy with ACE inhibitors, a dry cough may occur. The cough persists for a long time while taking drugs of this group and disappears after their discontinuation. If a patient develops a dry cough, one should be aware of the possibility of its occurrence in connection with taking an ACE inhibitor. If it is necessary to use drugs in this group, taking an ACE inhibitor can be continued.

Aortic and mitral stenosis, HOCM

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

Diabetes

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.

Surgery/general anesthesia

The use of ACE inhibitors in patients undergoing surgery under general anesthesia can lead to a significant decrease in blood pressure, especially when using general anesthetic agents that have antihypertensive effects. It is recommended to stop taking long-acting inhibitors, incl. perindopril, 24 hours before surgery.

Ethnic differences

In patients of the Negroid race, angioedema develops more often than in representatives of other races while using 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 black patients with arterial hypertension more often have low plasma renin activity.

Liver failure

In rare cases, cholestatic jaundice occurs while taking ACE inhibitors. As this syndrome progresses, fulminant liver necrosis develops, sometimes with death. The mechanism of development of this syndrome is unclear. If there is a significant increase in the activity of liver enzymes or the appearance of jaundice while taking ACE inhibitors, you should stop taking the drug and continue to monitor the patient.

Hyperkalemia

Hyperkalemia may develop while taking an ACE inhibitor. Risk factors for hyperkalemia are renal failure, old age (over 70 years), diabetes mellitus, some concomitant conditions (dehydration, acute decompensation of chronic heart failure, metabolic acidosis), simultaneous use of potassium-sparing diuretics (spironolactone, eplerenone, triamterene, amiloride), potassium supplements , potassium-containing substitutes for table salt, as well as other drugs that help increase the content of potassium in the blood plasma (for example, heparin) (especially in patients with reduced renal function). Hyperkalemia can lead to serious, sometimes fatal, heart rhythm disturbances. If necessary, simultaneous use of the drug with the above drugs should be used with caution and regularly monitor the potassium content in the blood plasma.

Renovascular hypertension

The treatment method for renovascular hypertension is renavascularization. However, the use of ACE inhibitors may be effective in patients with renovascular hypertension, both awaiting surgery and those who cannot undergo surgery.

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

Impact on the ability to drive vehicles and other technical devices

Due to the possibility of weakness and dizziness while using the drug Co-Dalneva®, care must be taken when driving vehicles and working with other technical devices that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms

The most likely symptoms of overdose are a pronounced decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (risk of severe and persistent arterial hypotension, including the development of 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). Disturbances in water and electrolyte balance (hyponatremia, hypokalemia) may also be observed.

Treatment

Emergency measures are aimed at removing the drug from the gastrointestinal tract: gastric lavage and/or taking activated carbon with subsequent restoration of water and electrolyte balance. If there is a pronounced decrease in blood pressure, the patient should be placed in an elevated position of the lower extremities, and, if necessary, correct hypovolemia (for example, 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.

Drug interactions

Amlodipine

Concomitant use is not recommended

Dantrolene (IV administration)

In laboratory animals, cases of ventricular fibrillation with death and collapse have been reported during the use of verapamil and intravenous administration of dantrolene, accompanied by hyperkalemia. Due to the risk of hyperkalemia, it is recommended to avoid the simultaneous use of BMCC (amlodipine) and dantrolene in patients susceptible to malignant hyperthermia, as well as in the treatment of malignant hyperthermia.

Concomitant use requiring special attention

Inducers of the CYP3A4 isoenzyme

There are no data regarding the effect of inducers of the CYP3A4 isoenzyme on amlodipine. The simultaneous use of inducers of the CYP3A4 isoenzyme (rifampicin, St. John's wort preparations) may lead to a decrease in the concentration of amlodipine in the blood plasma. Caution should be exercised when taking amlodipine simultaneously with inducers of the CYP3A4 isoenzyme.

CYP3A4 isoenzyme inhibitors

Concomitant use of amlodipine with strong or moderate inhibitors of the CYP3A4 isoenzyme (protease inhibitors, azole antifungals, macrolides, for example, erythromycin or clarithromycin, verapamil or diltiazem) can lead to a significant increase in the concentration of amlodipine. Clinical manifestations of these pharmacokinetic abnormalities may be more pronounced in elderly patients. In this regard, monitoring of the clinical condition and dose adjustment may be required.

Concomitant use requiring attention

Amlodipine enhances the antihypertensive effect of drugs for antihypertensive therapy.

Other drug combinations

In clinical drug interaction studies, amlodipine had no effect on the pharmacokinetics of atorvastatin, digoxin, warfarin or cyclosporine.

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

Indapamide

Concomitant use requiring special attention

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

Given the risk of developing hypokalemia, caution should be exercised when using indapamide simultaneously with drugs that can cause polymorphic ventricular tachycardia of the “pirouette” type, for example, antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide, amiodarone, dofetilide, ibutilide, bretylium tosylate, sotalol), some antipsychotics ( chlorpromazine, cyamemazine, levomepromazine, thiorylazine, trifluoroperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol), other antipsychotics (pimozide), other drugs such as bepridil, cisapride, difemanil methyl sulfate, erythromycin IV c, halofantrine, mizolastine, moxifloxacin, pentamidine, sparfloxacin, vincamine IV, methadone, astemizole, terfenadine. If hypokalemia develops, simultaneous use with the above drugs should be avoided, its correction should be carried out, and ECG (QT interval) monitoring should be monitored.

Drugs that can cause hypokalemia

Concomitant use with intravenous amphotericin B, systemic corticosteroids and mineralocorticosteroids, tetracosactide, laxatives that stimulate gastrointestinal motility increases the risk of hypokalemia (additive effect). It is necessary to monitor the potassium content in the blood plasma and, if necessary, correct hypokalemia. Particular caution should be observed when used simultaneously with cardiac glycosides. Laxatives that do not stimulate gastrointestinal motility should be used.

Cardiac glycosides

Hypokalemia enhances the toxic effect of cardiac glycosides. With simultaneous use, you should monitor the potassium content in the blood plasma and ECG indicators and, if necessary, decide on the advisability of continuing therapy.

Concomitant use requiring attention

Metformin

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

Iodinated contrast agents

Dehydration while taking diuretics increases the risk of developing acute renal failure, especially in

Side effects

Local allergic reactions, nausea, dyspepsia , diarrhea , weight change, tinnitus, agranulocytosis, leukopenia/neutropenia, thrombocytopenia, visual disturbances , headache , drowsiness , sleep disturbance , dizziness , insomnia , tremor , mood lability , fainting , palpitations, cough, shortness of breath , abdominal pain, vomiting, constipation , hepatitis , skin rash and itching, alopecia increased sweating , myalgia , photosensitivity , muscle spasms, arthralgia , frequent urination, peripheral edema , impotence , increased fatigue, asthenia , malaise.

Dalneva, instructions for use (Method and dosage)

Dalnev tablets are taken orally before meals, preferably before breakfast, 1 tablet once a day.

For patients with stable angina or arterial hypertension, the dose is selected based on the results of dose titration: amlodipine and perindopril . The maximum daily dosage of amlodipine is 10 mg; perindopril - 8 mg.

Dalneva should not be prescribed to patients with CC less than 60 ml/min. The use of Dalnev requires caution in patients with liver failure , since there are no recommendations on the dosage of the drug for such patients. Patients over 60 years of age do not require dose adjustment.

Compound

Interaction

When taking Dalneva together with Baclofen , there is a risk of increasing the hypotensive effect of the drug. With simultaneous use of the drug with drugs with a hypotensive effect, α-blockers ( Tamsulosin , alfuzosin , Prazosin , Terazosin , Doxazosin ), neuroleptics , general anesthesia, tricyclic antidepressants , an increase in the hypotensive effect and the development of orthostatic hypotension . Corticosteroids and tetracosactide reduce the hypotensive effect of Dalnev.

Analogues of Dalnev

Level 4 ATX code matches:
Tarka

Prestance

Drugs with similar therapeutic effects include: Amzaar , Amlodipine , Amlong , Vamloset , Duplekor , Kalchek , Lisinopril , Lizacard , Iruzid , Prestance , Liten , Rasilam , Tenliza , Equacard and others.

Dalneva price, where to buy

The price of Dalnev tablets 5 mg + 4 mg No. 30 varies between 385 - 590 rubles per pack. You can buy Dalnev without difficulty in most pharmacies in Moscow and other cities.

• Online pharmacies in RussiaRussia

ZdravCity

• Dalneva tab.
  10mg+ 8mg n30Krka-Rus LLC 555 RUR order
• Dalneva tab. 5mg+ 8mg n30Krka-Rus LLC

  RUR 564 order

• Dalneva tab. 5mg+ 4mg n30Krka-Rus LLC

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• KO-Dalneva tablets 5mg+1.25mg+4mg 30 pcs. Krka-Rus LLC

  RUR 546 order

• KO-Dalneva tablets 5mg+2.5mg+8mg 30 pcs. Krka-Rus LLC

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Description of the dosage form

Tablets 5 mg + 0.625 mg + 2 mg: oval, biconvex tablets with a score on one side, white or almost white.

Tablets 5 mg + 1.25 mg + 4 mg: round, slightly biconvex tablets with a bevel on both sides, white or almost white.

Tablets 5 mg + 2.5 mg + 8 mg: round, biconvex tablets with a bevel on both sides, white or almost white.

Tablets 10 mg + 1.25 mg + 4 mg: oval, biconvex tablets with a score on one side, white or almost white.

Tablets 10 mg + 2.5 mg + 8 mg: round, biconvex tablets with a bevel on both sides and a score on one side, white or almost white.