Dalneva - instructions for use, analogs, testimonials and release forms (tablets 5 mg + 4 mg, 10 mg + 4 mg, 5 mg + 8 mg, 10 mg + 8 mg, Ko-Dalnev) of the drug for reducing blood pressure in adults, children and during pregnancy. Composition

In this article, you can read the instructions for using the drug Dalnev. Presented are reviews of visitors to the site - consumers of this medication, as well as opinions of doctors of specialists on the use of Dalneva in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Dalnev analogues in the presence of existing structural analogs. Use to treat hypertension and reduce blood pressure in adults, children, as well as during pregnancy and lactation.Composition of the preparation.

Dalnev - Combined antihypertensive drug.

Perindopril

Perindopril is an ACE inhibitor. ACE or kinase 2 is an exopeptidase that converts angiotensin 1 into a vasoconstrictor substance - angiotensin 2, in addition, ACE destroys bradykinin, which has a vasodilating effect, to an inactive heptapeptide. The suppression of ACE activity leads to a decrease in angiotensin 2, an increase in renin activity in the blood plasma and a decrease in aldosterone secretion. Since ACE also destroys bradykinin, suppression of ACE leads to an increase in the activity of the kallikrein-kinin system.

Perindopril acts via its active metabolite, perindoprilat. Other metabolites have no inhibitory effect on ACE. Perindopril has a therapeutic effect at any degree of arterial hypertension, reducing systolic and diastolic blood pressure in a supine and standing position.

Reduces OPSS, resulting in increased peripheral blood flow without changes in the heart rate (heart rate).

Renal blood flow, as a rule, increases, while GFR does not change.

The hypotensive effect reaches its maximum after 4-6 hours after a single dose of perindopril in and maintained for 24 hours. The hypotensive effect at 24 h after a single oral administration is about 87-100% of the maximum hypertensive effect.

Reduction of blood pressure develops rapidly. The therapeutic effect occurs less than 1 month after the start of therapy and is not accompanied by tachycardia.

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

Perindopril has vasodilating effect, contributes to the restoration of elasticity and large arteries of the vascular wall structure of small arteries and reduces left ventricular hypertrophy.

Amlodipine

The dihydropyridine derivative, a blocker of slow calcium channels, has an antianginal and hypotensive effect. Blocking calcium channels, reduces the transmembrane passage of calcium ions into the cell (mainly in vascular smooth muscle cells than cardiac myocytes).

Antianginal effect is due to the expansion of coronary and peripheral arteries and arterioles: with angina decreases the severity of myocardial ischemia; expanding peripheral arterioles, reduces OPSS, reduces afterload on the myocardium, reduces the need for myocardium in oxygen,expanding coronary arteries and arterioles in unchanged and ischemic zones of the myocardium, increases the flow of oxygen into the myocardium (especially with vasospastic angina); prevents spasm of the coronary arteries (including caused by smoking). In patients with stable angina, a single daily dose increases exercise tolerance, increases the time until the onset of an attack of angina and ischemic depression of the ST segment on the ECG, reduces the incidence of angina attacks and the consumption of Nitroglycerin and other nitrates.

Has a long-term dose-dependent hypotensive effect. The hypotensive effect is due to a direct vasodilating effect on smooth muscle vessels. With arterial hypertension, a single dose provides a clinically significant decrease in blood pressure over a period of 24 hours (in the position of the patient lying down and standing). Orthostatic hypotension in the appointment of Amlodipine is rare. Does not cause a decrease in the fraction of the ejection of the left ventricle.

Reduces the degree of myocardial hypertrophy of the left ventricle. Does not affect the contractility and conductance of the myocardium, does not cause a reflex increase in heart rate, inhibits platelet aggregation, increases GFR, has a weak natriuretic effect.When diabetic nephropathy does not increase the severity of microalbuminuria. Does not have any adverse effect on the metabolism and concentration of plasma lipids and can be used in the treatment of patients with bronchial asthma, diabetes and gout. A significant reduction in blood pressure is observed after 6-10 h, the duration of the effect is 24 h.

Indapamide

Indapamide is a sulfonamide derivative. By pharmacological properties is close to thiazide diuretics (diuretic). Indapamide inhibits the reabsorption of sodium ions in the cortical segment of the Henle loop, which leads to an increase in the excretion of sodium and chloride ions by the kidneys, and to a lesser degree of potassium and magnesium ions, thereby increasing diuresis and lowering blood pressure.

In the regime of monotherapy, the antihypertensive effect persists for 24 hours and is manifested when the drug is used in doses that have a minimal diuretic effect. Antihypertensive effect of indapamide is associated with an improvement in the elastic properties of large arteries, a decrease in OPSS. Against the background of taking indapamide decreases LVH. Indapamide does not affect the concentration of lipids in the blood plasma (triglycerides, total cholesterol, HDL, LDL), the parameters of carbohydrate metabolism (including in patients with diabetes mellitus (DM).

Composition

Amlodipine besylate + Perindopril erbumine + excipients (Dalneva).

Amlodipine besylate + Perindopril erbumine + Indapamide + auxiliary substances (Co-Dalnev).

Pharmacokinetics

The amount of absorption of amlodipine and perindopril in the application of the Dal'nev preparation does not differ significantly from that of mono preparations.

Perindopril

After ingestion perindopril quickly absorbed and reaches Cmax in blood plasma for 1 hour. Food intake decreases the bioavailability of perindopril, so the drug should be taken 1 time per day, in the morning, before eating. There is a linear dependence of the concentration of perindopril in the blood plasma on the magnitude of its dose. Perindopril does not have pharmacological activity, it is a prodrug. Approximately 27% of the total amount of perindopril ingested enters the bloodstream as an active metabolite, perindoprilate. In addition to perindoprilata, another 5 metabolites are formed that do not have pharmacological activity. Cmax perindoprilata in blood plasma is achieved 3-4 hours after ingestion. Perindoprilat is excreted by the kidneys.

The excretion of perindoprilat is delayed in elderly patients and in patients with cardiac and renal insufficiency, so monitoring such patients should include regular monitoring of creatinine and potassium concentrations in the blood plasma.

The pharmacokinetics of perindopril has been changed in patients with liver cirrhosis: liver clearance decreases by a factor of 2, but the amount of perindoprilat formed does not decrease, so dose adjustment is not required.

Amlodipine

Amlodipine is well absorbed when ingested at therapeutic doses. Cmax in the blood plasma is achieved after 6-12 hours. Absolute bioavailability is 64-80%. Eating food does not affect the bioavailability of amlodipine. Metabolized in the liver with the formation of inactive metabolites. Approximately 60% of the accepted dose is excreted by the kidneys, 10% - unchanged.

Indapamide

Indapamide is rapidly and completely absorbed from the digestive tract. The degree of binding to plasma proteins is 79%. Repeated reception of indapamide does not lead to its cumulation. It is excreted mainly by the kidneys (70% of the dose taken internally) and through the intestine (22%) in the form of inactive metabolites.

Indications

arterial hypertension and / or IHD: stable angina in patients requiring perindopril and amlodipine therapy.

Forms of release

Tablets 5 mg + 4 mg, 10 mg + 4 mg, 5 mg + 8 mg, 10 mg + 8 mg (Dalnev).

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 (Co-Dalnev).

Instructions for use and dosage

Dalneva tablets

The drug is taken orally, 1 tablet once a day, preferably in the morning before eating.

The dose of the drug Dalnev is selected after previous titration of the doses of individual components of the drug: perindopril and amlodipine in patients with arterial hypertension and stable angina.

If necessary, the dose of the drug Dalnev can be changed on the basis of individual selection of doses of individual components: (amlodipine 5 mg + perindopril 4 mg) or (amlodipine 10 mg + perindopril 4 mg) or (amlodipine 5 mg + perindopril 8 mg) or (amlodipine 10 mg + perindopril 8 mg).

The maximum daily dose: amlodipine 10 mg + perindopril 8 mg.

When using the drug Dalnev in elderly patients, dose adjustment is not required.

Tablets of Ko-Dalnev

Inside, 1 tablet 1 time per day, preferably in the morning, before eating.

The dose of Ko-Dalnev preparation is selected after previous titration of doses of active components of the drug. The maximum daily dose of the drug Ko-Dalnev is 8 mg perindopril + 2.5 mg indapamide + 10 mg amlodipine.

It is not necessary to change the dosage regimen in elderly patients, but the dose should be increased with caution, which is associated with age-related changes and an elongation of the half-life.

Side effect

neutropenia, agranulocytosis, pancytopenia, thrombocytopenia;
hemolytic anemia in patients with congenital deficiency of glucose-6-phosphate dehydrogenase;
reduction of hemoglobin and hematocrit;
hives;
increase in body weight;
decrease in body weight;
drowsiness;
dizziness;
headache;
paresthesia;
insomnia;
mood lability;
sleep disturbance;
tremor;
peripheral neuropathy;
confusion of consciousness;
visual impairment;
noise in ears;
a feeling of palpitations;
flushes of blood to the skin of the face;
marked decrease in blood pressure;
fainting;
pain behind the sternum;
angina pectoris;
myocardial infarction, possibly due to excess BP reduction in patients at high risk;
arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation);
stroke, possibly due to excess BP reduction in patients at high risk;
vasculitis;
dyspnea;
cough;
rhinitis or rhinitis;
bronchospasm;
eosinophilic pneumonia;
abdominal pain;
nausea, vomiting;
dyspepsia;
diarrhea, constipation;
dryness of the oral mucosa;
violation of taste perception;
change in the rhythm of defecation;
pancreatitis;
gingival hyperplasia;
gastritis;
hepatitis;
cholestatic jaundice;
cytolytic or cholestatic hepatitis;
itching;
skin rash;
angioedema, swelling of the face, limbs, lips, mucous membranes, tongue, vocal cords and / or larynx;
alopecia;
hemorrhagic rash;
photosensitization;
increased sweating;
angioedema;
erythema multiforme;
Stevens-Johnson syndrome;
muscle spasms;
arthralgia;
myalgia;
backache;
violation of urination;
frequent urination;
kidney failure;
impotence;
gynecomastia;
asthenia;
increased fatigue;
pain in the chest.

Contraindications

Perindopril

angioedema (angioedema) (angioedema) in the anamnesis (including against the background of taking other ACE inhibitors);
hereditary / idiopathic angioedema;
age under 18 years (effectiveness and safety not established);
hypersensitivity to perindopril or other ACE inhibitors.

Amlodipine

severe arterial hypotension (systolic blood pressure less than 90 mm Hg);
shock, including cardiogenic shock;
obstruction of the left ventricular outflow tract (eg, severe aortic stenosis);
unstable angina (with the exception of Prinzmetal's stenocardia);
age under 18 years (effectiveness and safety not established);
hemodynamically unstable heart failure after acute myocardial infarction;
hypersensitivity to amlodipine or other dihydropyridine derivatives.

Indapamide

anuria;
hypokalemia;
expressed hepatic (including with encephalopathy) and / or renal failure;
pregnancy;
lactation period;
age under 18 years (effectiveness and safety not established);
simultaneous reception of drugs that extend the QT interval;
hypersensitivity to the drug and other sulfonamide derivatives.

Application in pregnancy and lactation

The use of the drug Dalnev is contraindicated in pregnancy.

The drug should not be used in the 1st trimester of pregnancy. When planning a pregnancy or when it comes on the background of the use of the drug, it is necessary to stop taking it as soon as possible and to prescribe another hypotensive therapy that has been approved for use during pregnancy. Appropriate controlled trials of the use of ACE inhibitors in pregnant women have not been conducted. The available limited data on the effect of the drug on the fetus in the first trimester of pregnancy indicate that the use of ACE inhibitors does not lead to fetal malformations, but the increase in risk can not be ruled out. It is known that the effect of ACE inhibitors on the fetus in the 2nd and 3rd trimesters of pregnancy can lead to disruption of its development (decreased kidney function, oligohydramnion, delayed ossification of the skull bones) and development of complications in the newborn (kidney failure, arterial hypotension, hyperkalemia).If the patient received ACE inhibitors in the 2 or 3 trimesters of pregnancy, it is recommended that ultrasound be performed to assess the condition of the skull bones and the function of the kidneys of the fetus.

Newborns whose mothers received ACE inhibitors in pregnancy should be under close medical supervision because of the risk of developing arterial hypotension, oliguria, and hyperkalemia.

It is not recommended to use the drug Dalnev during lactation, tk. There is no relevant clinical experience with amlodipine and perindopril in either monotherapy or combination therapy. If you need to use the drug Dalnev during lactation breastfeeding should be discontinued.

Use in children

The drug Dalnev and Co-Dalnev should not be administered to children and adolescents under the age of 18, there are no data on the efficacy and safety of perindopril and amlodipine in these groups of patients, both in monotherapy and in combination therapy.

Application in elderly patients

When using the drug in elderly patients, dose adjustment is not required. Take care when increasing dosages.

special instructions

Special instructions relating to amlodipine and perindopril apply to the drug Dalnev.

Perindopril

Hypersensitivity / angioedema (angioedema)

With the use of ACE inhibitors, incl. perindopril, in rare cases, development of an angioedema of the face, lips, tongue, vocal cords, and / or larynx can be observed. When these symptoms appear, the use of the Dal'nev preparation should be stopped immediately; The patient should be monitored until the signs of edema disappear completely.

If angioedema affects only the face and lips, then its manifestations usually go away alone or antihistamines may be used to treat its symptoms. Angioedema, accompanied by swelling of the tongue or larynx, can lead to airway obstruction and death. If such symptoms appear, immediately inject epinephrine (adrenaline) in the dilution 1: 1000 (0.3 or 0.5 ml) and / or provide airway patency. The patient should be under medical supervision until the symptoms disappear completely and persistently.

Patients with a history of Quincke edema not associated with the use of ACE inhibitors may be at increased risk of developing it with the use of drugs of this group.

In rare cases, against the background of therapy with ACE inhibitors, angioedema develops in the intestine. In this case, patients have abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without a previous angioedema and at a normal level of C-1-esterase. The diagnosis is established using computed tomography of the abdominal cavity, ultrasound or at the time of surgery. Symptoms disappear after the cessation of the use of ACE inhibitors. In patients with abdominal pain receiving ACE inhibitors, the differential diagnosis should take into account the possibility of developing angioedema of the intestine.

Anaphylactoid reactions during desensitization procedures

There are separate reports on the development of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with the Hymenoptera (Hymenoptera) venom.ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. The appointment of an ACE inhibitor should be avoided for patients receiving immunotherapy with venom of Hymenoptera. Nevertheless, the development of anaphylactoid reactions can be avoided by the temporary withdrawal of the ACE inhibitor at least 24 hours before the desensitization procedure begins.

Anaphylactic reactions during an apheresis of LDL with dextran sulfate

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

Hemodialysis

In patients receiving ACE inhibitors, anaphylactoid reactions were observed in hemodialysis using high-flow membranes (eg AN69). Therefore, it is desirable to use a different type of membrane and use an antihypertensive drug of another pharmacotherapeutic group.

Neutropenia / agranulocytosis, thrombocytopenia and anemia

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

Perindopril should be used with great care in patients with connective tissue diseases and simultaneously receiving immunosuppressive therapy, Allopurinol or procainamide, especially with existing renal dysfunction. Some patients may develop severe infections that are not amenable to intensive antibiotic therapy. In the case of the appointment of perindopril, it is recommended to control the number of leukocytes in the blood plasma. The patient should be warned that if any signs of an infectious disease (sore throat, fever) should be consulted.

The risk of arterial hypotension and / or renal failure (including in patients with chronic heart failure, a violation of the water-electrolyte balance)

With cirrhosis of the liver, accompanied by edema and ascites, arterial hypotension,chronic heart failure may show a significant activation of RAAS, especially in severe hypovolemia and a decrease in the content of electrolytes in blood plasma (against a background of diets with restriction of table salt of long-term intake of diuretics).

The use of an ACE inhibitor causes blockade of the RAAS; in this connection, a sharp decrease in blood pressure and / or an increase in the plasma creatinine concentration, which indicates the development of acute renal failure, is more likely to occur with the first dose or during the first 2 weeks of therapy with Dalnev.

ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic arterial hypotension rarely occurs in patients without concomitant diseases. The risk of excessive reduction in blood pressure is increased in patients with reduced BCC, which can be observed against diuretic therapy, with a strict diets with restriction of table salt, hemodialysis, with diarrhea or vomiting, or in patients with severe hypertension with high renin activity. Patients with a high risk of symptomatic arterial hypotension should carefully monitor blood pressure, kidney function and potassium in the blood serum during therapy with Dalnev.

The same precautions apply to patients with angina or cerebrovascular disease, in whom a marked decrease in blood pressure may lead to the development of myocardial infarction or impaired cerebral circulation.

In the case of development of arterial hypotension, the patient should be transferred to a horizontal position with a low headboard. If necessary, fill the bcc with intravenous injection of 0.9% sodium chloride solution. Transient arterial hypotension is not a contraindication for the further use of the drug Dalnev. After the recovery of bcc and AD, treatment with Dalnev can be continued.

Aortic stenosis / mitral stenosis / hypertrophic obstructive cardiomyopathy

ACE inhibitors should be used with caution in patients with obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as in patients with mitral stenosis.

Potassium-sparing diuretics and potassium preparations

Simultaneous use of perindopril and potassium-sparing diuretics, as well as potassium and potassium-containing substitutes for table salt is not recommended.

Cough

Against the background of therapy with an ACE inhibitor, a dry, unproductive cough may occur that disappears after the withdrawal of this group. When dry cough occurs, remember the possible association of this symptom with the use of an ACE inhibitor.

Impaired renal function

If the kidney function is impaired (CC less than 60 ml / min), individual doses of perindopril and amlodipine are recommended. Regular monitoring of potassium and creatinine levels in blood plasma is a prerequisite for the treatment of such patients. In some patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney, taking ACE inhibitors, there was an increase in urea and creatinine levels in the blood plasma, reversible after the withdrawal of therapy. These changes are more likely in patients with renal insufficiency. In patients with renovascular hypertension, there is an increased risk of severe arterial hypotension and renal failure. In some patients with arterial hypertension without obvious signs of existing kidney diseases who were taking perindopril concomitantly with a diuretic, there was a small and temporary increase in the concentration of urea and creatinine in the serum.These changes often develop in patients with a previous impairment of kidney function.

Impaired liver function

Rarely, the use of ACE inhibitors is accompanied by a syndrome, the development of which begins with cholestatic jaundice and which then progresses to fulminant liver necrosis, sometimes fatal. The mechanism of development of this syndrome is unclear. If, during the use of an ACE inhibitor, jaundice occurs or liver transaminase activity increases, the ACE inhibitor should be immediately discontinued and the patient must remain under appropriate medical supervision.

Ethnic Features

In patients of the Negroid race more often than in the representatives of other races, against the background of the use of ACE inhibitors, angioedema develops. Perindopril, like other ACE inhibitors, may have a less pronounced hypotensive effect in patients of the Negroid race compared to representatives of other races. Perhaps this difference is due to the fact that patients with arterial hypertension of the Negroid race are more likely to have low renin activity of the blood plasma.

Surgical interventions / general anesthesia

The use of ACE inhibitors in patients undergoing extensive surgery and / or general anesthesia can lead to a marked decrease in blood pressure if general anesthetics with hypotensive action are used. This is due to the blocking of the formation of angiotensin 2 against a background of compensatory enhancement of renin activity. If the development of arterial hypotension is associated with the mechanism described, the BCC should be increased. It is recommended that the drug be discontinued 24 hours before surgery.

Hyperkalemia

Against the background of therapy with ACE inhibitors, including perindopril, in some patients, the potassium content in the blood plasma may increase. Risk factors for hyperkalemia include renal failure, impaired renal function, advanced age (over 70 years), diabetes mellitus, intercurrent conditions, in particular, dehydration, acute cardiac decompensation, metabolic acidosis, simultaneous use of potassium-sparing diuretics (eg spironolactone, eplerenone, triamterene or amiloride), drugs or additives with a potassium content,potassium-containing substitutes for edible salt or simultaneous use of other drugs that increase the potassium content in the blood plasma (eg, heparin). Hyperkalemia can cause serious, sometimes life-threatening arrhythmias. If you need to simultaneously use perindopril and one of the above means, you should be careful and regularly monitor the potassium content in the blood plasma.

Patients with diabetes mellitus

In patients with diabetes who take hypoglycemic agents for ingestion and / or insulin, in the first few months of therapy with ACE inhibitors, increased monitoring of blood glucose levels is necessary.

Amlodipine

Impaired liver function

In patients with impaired hepatic T1 / 2 function, amlodipine is prolonged. When prescribing the drug, such patients should be careful and regularly monitor the activity of liver enzymes.

Patients with heart failure

In patients with chronic heart failure (grades 3 and 4 of the NYHA classification class), treatment should be carried out with caution in connection with the possibility of developing pulmonary edema.

Impact on the ability to drive vehicles and manage mechanisms

In connection with the possibility of dizziness and other side effects on the background of using the drug Dal'nev, care must be taken when driving vehicles and working with other technical devices that require an increased concentration of attention and speed of psychomotor reactions.

Drug Interactions

Perindopril

Unsupported combinations

Potassium-sparing diuretics, potassium preparations or potassium-containing substitutes for edible salt: although the serum potassium content remains within normal limits, some patients may experience hyperkalemia with perindopril. Potassium-sparing diuretics (eg, spironolactone, triamterene or amiloride), potassium preparations or potassium-containing substitutes for edible salt can lead to a significant increase in potassium levels in the blood plasma, so their use concomitantly with ACE inhibitors is not recommended. If simultaneous therapy is necessary (in case of confirmed hypokalemia), care should be taken and regular monitoring of potassium content in plasma and ECG parameters should be carried out.

Lithium preparations: with simultaneous use of lithium preparations and ACE inhibitors, cases of reversible increase in serum lithium concentration and associated toxic effects were recorded. Simultaneous therapy with perindopril and lithium preparations is not recommended. If necessary, combined therapy should be carried out under regular control of the concentration of lithium in blood plasma.

Estramustine: simultaneous use is accompanied by an increased risk of angioedema.

Combinations requiring special care

Nonsteroidal anti-inflammatory drugs (NSAIDs), incl. inhibitors of COX-2, Acetylsalicylic acid in high doses (more than 3 g per day) and nonselective NSAIDs: the use of NSAIDs may lead to a decrease in the diuretic, natriuretic and hypotensive effects of ACE inhibitors. Simultaneous use of ACE inhibitors and NSAIDs can lead to impaired renal function, including the development of acute renal failure and an increase in potassium in the blood serum, especially in patients with reduced renal function.Care should be taken when using this combination, especially in elderly patients. Patients in this case need to compensate for the loss of fluid to closely monitor kidney function, both at the beginning of treatment and during treatment.

Hypoglycemic drugs (for ingestion and / or insulin): the use of ACE inhibitors can enhance the hypoglycemic effect of insulin or sulfonylurea derivatives in patients with diabetes mellitus. The development of episodes of hypoglycemia was noted very rarely (possibly there is an increase in glucose tolerance, leading to a decrease in the need for insulin).

Combinations that require attention

Diuretics (thiazide and loop): in patients taking diuretics, especially when excess fluid and / or electrolytes are removed, a significant reduction in blood pressure can occur at the onset of the use of ACE inhibitors. The risk of developing arterial hypotension can be reduced by eliminating the diuretic, increasing fluid intake and / or table salt before starting therapy, starting therapy with low doses of perindopril with a further gradual increase.

Sympathomimetics: sympathomimetics can weaken the hypotensive effect of ACE inhibitors.

Gold preparations: patients who receive simultaneous injection therapy with gold preparations (sodium aurothiomalate) and ACE inhibitors, including perindopril, rarely notice nitrate-like reactions (blood flushes to the skin of the face, nausea, vomiting, lowering blood pressure).

Allopurinol, cytostatic and immunosuppressive agents, glucocorticosteroids (GCS) (for systemic use) and procainamide: simultaneous use with ACE inhibitors may be accompanied by an increased risk of leukopenia.

Means for general anesthesia: simultaneous use of ACE inhibitors and agents for general anesthesia can lead to an increase in the hypotensive effect.

Amlodipine

Unsupported combinations

Dantrolene (IV introduction): in experiments on animals after the administration of Verapamil and dantrolene (intravenously), cases of ventricular fibrillation with a lethal outcome and cardiovascular insufficiency associated with hyperkalemia were observed. Given the risk of hyperkalemia, simultaneous use of slow calcium channel blockers should be avoided, including.and amlodipine, and dantrolene.

Combinations requiring special care

Inductors CYP3A4 (rifampicin, St. John's wort preparations, anticonvulsants such as carbamazepine, phenobarbital, phenytoin, phosphenytoin, primidone): it is possible to reduce the plasma concentration of amlodipine due to increased metabolism in the liver. Caution should be exercised with the simultaneous use of amlodipine and inducers of microsomal oxidation and, if necessary, adjust the dose of amlodipine.

Strong and moderate inhibitors of the isoenzyme CYP3A4 (protease inhibitors, azole antifungals (itraconazole and ketoconazole), macrolide antibiotics such as Erythromycin and clarithromycin, and verapamil and diltiazem): an increase in plasma concentrations of amlodipine and an increased risk of side effects , especially in elderly patients. Caution should be exercised with simultaneous use and, if necessary, adjust the dose of amlodipine.

Combinations that require attention

Simultaneous application of beta-blockers (bisoprolol, metoprolol) and alfa-and beta-adrenoblocker carvedilol,used in chronic heart failure: increases the risk of developing arterial hypotension and worsening of the course of chronic heart failure in patients with uncontrolled or latent chronic heart failure (increased inotropic effect). In addition, beta-blockers can reduce excessive reflex cardiac sympathetic activation against the background of concomitant chronic heart failure.

Other combinations

In monotherapy, amlodipine is safe to use concomitantly with thiazide diuretics, beta-blockers, ACE inhibitors, prolonged-action nitrates, nitroglycerin (for sublingual use), digoxin, warfarin, atorvastatin, sildenafil, antacids (aluminum hydroxide colloid, magnesium hydroxide), simethicone, cimetidine, NSAIDs, antibiotics and hypoglycemic agents for oral administration.

There is no interaction of the following drugs with amlodipine:

with the simultaneous use of amlodipine and cimetidine pharmacokinetic parameters of amlodipine did not change;
with the simultaneous use of amlodipine and sildenafil, there was no increase in the hypotensive effect of each drug;
taking 240 ml of grapefruit juice together with a single dose of amlodipine (10 mg orally) had no significant effect on the pharmacokinetics of amlodipine.

Amlodipine does not affect the pharmacokinetics of the following drugs:

atorvastatin: repeated administration of amlodipine at a dose of 10 mg in combination with atorvastatin at a dose of 80 mg does not lead to a significant change in the pharmacokinetic parameters of atorvastatin in the equilibrium state;
digoxin: simultaneous use of amlodipine and digoxin is not accompanied by a change in serum digoxin concentration and renal clearance of digoxin in healthy volunteers;
warfarin: in healthy male volunteers taking warfarin, the addition of amlodipine does not significantly affect the change in the prothrombin time indicator due to warfarin;
cyclosporine: amlodipine does not significantly affect the pharmacokinetic parameters of cyclosporine.

Indapamide

A simultaneous application requiring special attention

Preparations that can cause polymorphic ventricular tachycardia of the "pirouette" type. Given the risk of hypokalemia, caution should be exercised when using indapamide with drugs that can induce polymorphic ventricular tachycardia such as pirouettes, for example antiarrhythmics (quinidine, hydroquinidine, disopyramide, amiodarone, dofetilide, ibutilide, brethil tosylate, sotalol), some neuroleptics chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoroperazine), benzamides (amisulpride, sulpiride, sultopride, tiaprid), butyrophenones (droperidol, haloperidol), others roleptics (pimozide), other drugs such as bepridil, cisapride, dipemannil methyl sulfate, erythromycin iv, halofantrine, misolastine, moxifloxacin, pentamidine, sparfloxacin, winkamine I, methadone, astemizole, terfenadine. It should avoid simultaneous use with the above drugs, with the development of hypokalemia, carry out its correction, monitor the ECG (QT interval).

Drugs that can cause hypokalemia. Simultaneous reception with amphotericin B in the IV, systemic SCS and mineralocorticosteroids, tetracosactide,laxatives, stimulating the motility of the gastrointestinal tract, increases the risk of hypokalemia (additive effect). It is necessary to control the content of potassium in the blood plasma, if necessary - correction of hypokalemia. Particular care should be taken when using with cardiac glycosides. You should use laxatives that do not stimulate the motility of the gastrointestinal tract.

Cardiac glycosides. Hypokalemia increases the toxic effect of cardiac glycosides. In case of simultaneous use, it is necessary to monitor the potassium content in the blood plasma and the ECG parameters and, if necessary, to decide whether to continue the therapy.

Simultaneous application requiring attention

Metformin. Functional renal failure, which can occur with the use of diuretics, especially loop, with the simultaneous use of Metformin increases the risk of lactic acidosis. Do not use metformin if the creatinine clearance in the blood plasma is greater than 15 mg / L (135 μmol / L) in men and 12 mg / L (110 μmol / L) in women.

Iodine-containing contrast agents. Dehydration of the body against the background of 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, hypovolemia should be compensated.

Salts of calcium. With simultaneous application, it is possible to develop hypercalcemia due to a reduction in the excretion of calcium by the kidneys.

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

Dalnev

Combinations that require special attention

Baclofen: Potentiation of hypotensive effect is possible. It is necessary to monitor blood pressure and kidney function, as well as dose adjustment of amlodipine.

Combinations that require attention

Antihypertensive drugs (for example, beta-blockers) and vasodilators: it is possible to intensify the hypotensive effect of perindopril and amlodipine.

Caution should be exercised when using nitroglycerin, other nitrates or other vasodilators at the same time, as there may be an additional reduction in blood pressure.

Corticosteroids (mineral and glucocorticosteroids), tetracosactide: a decrease in hypotensive action (fluid retention and sodium ions due to the action of corticosteroids).

Alpha-adrenoblockers (prazosin, alfuzozin, doxazosin, tamsulosin, terazosin): increased hypotensive effect and increased risk of orthostatic hypotension.

Amifostin: can potentiate the hypotensive effect of amlodipine.

Tricyclic antidepressants / antipsychotics / drugs for general anesthesia: increased hypotensive effect and increased risk of orthostatic hypotension.

Ko-Dalnev

Simultaneous use is not recommended

Lithium preparations. With the simultaneous use of ACE inhibitors with lithium preparations, a reversible increase in the concentration of lithium in blood plasma can occur with the development of intoxication. Simultaneous use with thiazide diuretics can further increase the concentration of lithium and increase the risk of intoxication. The simultaneous use of a combination of perindopril and indapamide with lithium preparations is not recommended. In the case of this therapy, regular monitoring of the concentration of lithium in the blood plasma is necessary.

A simultaneous application requiring special attention

Baclofen. Perhaps increased antihypertensive effect.It is necessary to monitor blood pressure and kidney function, if necessary, adjust the dose of antihypertensive drugs.

Simultaneous application requiring attention

Hypotensive drugs (eg, beta-blockers) and vasodilators. With simultaneous use with antihypertensive drugs, it is possible to increase the antihypertensive effect. Caution should be exercised when using nitroglycerin, other nitrates or other vasodilators at the same time, as there may be an additional reduction in blood pressure.

Corticosteroids (mineral and glucocorticosteroids), tetracosactide. Reduction of antihypertensive action (fluid retention and sodium as a result of corticosteroids).

Alpha-adrenoblockers (prazosin, alfuzozin, doxazosin, tamsulosin, terazosin). Increased antihypertensive action and increased risk of orthostatic hypotension.

Amifostin. It is possible to increase the antihypertensive effect of amlodipine.

Tricyclic antidepressants / antipsychotics / agents for general anesthesia. Increased antihypertensive action and increased risk of orthostatic hypotension (additive effect).

Analogues of the drug Dalnev

Structural analogs for the active substance:

Amlodipine + Perindopril;
Amlopress;
Ko-Dalnev;
Parnavel Amlo.

Analogues on the curative effect (means for the treatment of hypertension):

Adelphan Ezidrex;
Akkupro;
Amlodipine;
Amprilan;
Anaprilin;
Atenolol;
Berlipril;
Betalk;
Bisoprolol;
Wales H;
Verapamil;
Veroshpiron;
Hypothiazide;
Diltiazem;
Diroton;
The Zocardis;
Indap;
Indapamide;
Captopril;
Carvedilol;
Clopheline;
Concor;
Corvitol;
Cordaflex;
Cordipine;
Corinfar;
Lysinopril;
Lozap;
Losartan;
Lorist;
Metoprolol;
Non-ticket;
Nifedipine;
Noliprel;
Noliprel forte;
Norvasc;
Obsidan;
Prestan;
Prestarium;
Ramipril;
Raunatin;
Renitek;
Spironolactone;
Stamlo;
Physiotherapy;
Fosicard;
Furosemide;
Egilok;
Equator;
Exforge;
Enalapril;
Enam;
Enap;
Enap H;
Enziks;
Estecor.

If there are no analogues of the medication for the active substance, you can go to the links below for diseases, from which the corresponding drug helps, and to look at the available analogs for therapeutic effects.

Used for the treatment of diseases: hypertension, pressure, arterial hypertension, angina pectoris, cardiac ischemia, essential hypertension, stable angina, essential hypertension, ibs, angina pectoris