Dalneva pills 5mg + 8mg №90

Drug name

Dal'neva ^®, pills

Qualitative and quantitative composition

Pharmaceutical form

Tablets of 5 mg + 4 mg: Round, slightly biconvex pills with a facet, white or almost white color.

Tablets 10 mg + 4 mg: Capsule, biconvex pills with a risk on one side, white or almost white.

Tablets of 5 mg + 8 mg: Round, biconvex pills with a facet, white or almost white color.

Tablets 10 mg + 8 mg: Round, biconvex pills with a facet and a risk on one side, white or almost white.

Clinical data

Indications for use

• Arterial hypertension and / or coronary heart disease: stable exertional angina in patients who require perindopril and amlodipine.

Contraindications

Perindopril

Increased sensitivity to perindopril or other ACE inhibitors;

- angioedema (angioedema) in history (including the background of taking other ACE inhibitors);

- hereditary / idiopathic angioedema;

- age up to 18 years (efficacy and safety have not been established);

Amlodipine

- hypersensitivity to amlodipine or other dihydropyridine derivatives;

- severe arterial hypotension (systolic blood pressure less than 90 mm Hg), shock, including cardiogenic shock;

- obstruction of the output tract of the left ventricle (for example, severe aortic stenosis);

Unstable angina (with the exception of Prinzmetal stenocardia);

- age up to 18 years (efficacy and safety have not been established);

- hemodynamically unstable heart failure after acute myocardial infarction.

Dal'neva^®

Increased sensitivity to excipients that are part of the drug;

- renal insufficiency (creatinine clearance (CC) less than 60 ml / min);

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

Carefully: hepatic insufficiency, chronic heart failure (CHF), aortic and / or mitral stenosis, hypertrophic obstructive cardiomyopathy (GOKMP), old age, bilateral stenosis of the renal arteries, stenosis of the only functioning kidney, renal failure (CC less than 60 ml / min), systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), therapy with immunosuppressants, Allopurinol, procainamide (risk of developing neutropenia, agranulocytosis), reduced circus decaying blood (BCC) (diuretic intake, diet with restricted salt, vomiting, diarrhea), atherosclerosis, cerebrovascular diseases, renovascular hypertension, diabetes mellitus, use of dantrolene, estramustine, potassium-saving diuretics, potassium, potassium, potassium, potassium, potassium, potassium, potassium, potassium, diarrhea hyperkalemia, surgery / general anesthesia, use of the Negroid race in patients, hemodialysis using high-flow polyacrylonitrile membranes - the risk of anaf ilaktoidnyh reactions; before the procedure of low density lipoprotein apheresis (LDL) using dextran sulfate, simultaneous desensitization therapy with allergens (for example, hymenoptera), the state after kidney transplantation (no clinical data).

Pregnancy and breastfeeding

Pregnancy

Dalnev drug use^® contraindicated in pregnancy.

Drug Dalneva ^® should not be used in the first trimester of pregnancy. When planning a pregnancy or when it occurs on the background of the use of the drug Dalneva^®, it is necessary to stop taking the drug as soon as possible and prescribe another antihypertensive therapy approved for use during pregnancy. Appropriate controlled studies of the use of ACE inhibitors in pregnant women have not been conducted.The limited data available on the effects 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 an increase in risk cannot be excluded.

It is known that the effect of ACE inhibitors on the fetus in the second and third trimesters of pregnancy can lead to impaired development (reduced kidney function, oligohydramnios, slowing down the ossification of the skull bones) and the development of complications in the newborn (renal failure, arterial hypotension). If the patient received ACE inhibitors in the II or III trimester of pregnancy, it is recommended to conduct an ultrasound examination to assess the state of the bones of the skull and the kidney function of the fetus.

Newborns whose mothers received ACE inhibitors during pregnancy should be under close medical supervision due to the risk of arterial hypotension, oliguria and hyperkalemia.

Breastfeeding period

Do not use the drug Dalneva^® during lactation, because there is no relevant clinical experience with the use of amlodipine and perindopril both in monotherapy and in combination therapy. If necessary, use the drug Dalneva^® during lactation, breastfeeding should be discontinued.

Dosage and administration

Inside, one tablet 1 time per day, preferably in the morning before a meal.

Dose of the drug Dalneva^® It is selected after previous titration of 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 Dalneva^® 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).

Maximum daily dose: amlodipine 10 mg + perindopril 8 mg.

Renal dysfunction

Drug Dalneva^® can be used in patients with QA more than 60 ml / min.

Drug Dalneva^® contraindicated for use in patients with QA less than 60 ml / min. Such patients are recommended individual selection of doses of perindopril and amlodipine.Changes in the concentration of amlodipine in the blood plasma do not correlate with the severity of renal failure.

Liver failure

Care must be taken when using the drug Dalneva^® patients with liver failure, because there are no recommendations for the drug doses in these patients.

Elderly patients

When using the drug Dalneva^® elderly patients dose adjustment is not required.

Kids and teens

Drug Dalneva^® should not be assigned to children and adolescents under 18 years, because there are no data on the efficacy and safety of perindopril and amlodipine in these groups of patients both in monotherapy and as part of combination therapy.

Side effect

Classification of the incidence of side effects of the World Health Organization (WHO):

very often ≥1 / 10

often from ≥1 / 100 to <1/10

infrequently from ≥1 / 1000 to <1/100

rarely from ≥1 / 10,000 to <1/1000

very rarely from <1/10000

frequency unknown cannot be estimated based on available data.

In each group, undesirable effects are presented in order of decreasing severity.

From the circulatory and lymphatic systems:

very rare: leukopenia / neutropenia, agranulocytosis, pancytopenia, thrombocytopenia, hemolytic anemia in patients with congenital glucose-6-phosphate dehydrogenase deficiency, decreased hemoglobin and hematocrit.

On the part of the immune system:

infrequently: urticaria.

Metabolic disorders:

infrequently: weight gain, weight loss;

very rare: hyperglycemia.

frequency unknown: hypoglycemia.

The nervous system:

often: drowsiness, dizziness, headache, paresthesias, vertigo;

infrequently: insomnia, mood lability, sleep disturbance, tremor, hypoesthesia;

very rare: peripheral neuropathy, confusion.

From the senses:

often: visual disturbances, tinnitus;

Since the cardiovascular system:

often: a feeling of heartbeat, "flushes" of blood to the skin of the face, a pronounced decrease in blood pressure;

infrequently: fainting;

seldom: pain behind the sternum;

very rarely: angina pectoris, myocardial infarction, possibly due to an excessive decrease in blood pressure in high-risk patients, arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), stroke, possibly due to an excessive decrease in blood pressure in high-risk patients, vasculitis.

On the part of the respiratory system:

often: shortness of breath, cough;

infrequently: rhinitis, bronchospasm;

very rarely: eosinophilic pneumonia.

From the digestive system:

often: abdominal pain, nausea, vomiting, dyspepsia, diarrhea, constipation;

infrequently: dryness of the oral mucosa, a violation of taste perception, a change in the rhythm of defecation;

very rarely: pancreatitis, gingival hyperplasia, gastritis, hepatitis, cholestatic jaundice, cytolytic or cholestatic hepatitis.

On the part of the skin:

often: skin itch, skin rash;

infrequently: angioedema of the face, extremities, lips, mucous membranes, tongue, vocal folds and / or larynx, alopecia, hemorrhagic rash, photosensitization, increased sweating;

very rarely: angioedema, erythema multiforme, Stevens-Johnson syndrome.

From the musculoskeletal system:

often: muscle spasms;

infrequently: arthralgia, myalgia, back pain.

From the urinary system:

infrequently: violation of urination, nocturia, frequent urination, renal failure;

very rare: acute renal failure .

From the reproductive system:

infrequently: impotence, gynecomastia.

Other:

often: peripheral edema, asthenia, fatigue;

infrequently: chest pain, malaise.

Laboratory values:

rarely: increased bilirubin concentration;

very rarely: increased activity of liver transaminases: aspartate aminotransferase (AST), alanine aminotransferase (ALT) (most often in combination with cholestasis);

frequency unknown: increase in the concentration of urea and creatinine in the serum.

Additional data on amlodipine: isolated cases of extrapyramidal syndrome have been reported with the use of slow Calcium channel blockers.

Overdose

Information about overdose drug Dalneva^® missing.

Perindopril

Data on overdose with perindopril is limited.

Symptoms: marked reduction in blood pressure, shock, impaired water and electrolyte balance, renal failure, hyperventilation, tachycardia, feeling of heartbeat, bradycardia, dizziness, anxiety and cough.

Treatment: emergency measures are reduced to the removal of the drug from the body: gastric lavage and / or the appointment of activated charcoal with the subsequent restoration of the BCC.

With a pronounced decrease in blood pressure, the patient should be placed in the "lying" position on the back with raised legs, and if necessary, measures should be taken to restore the BCC (for example, intravenous infusion with 0.9% sodium chloride solution). Intravenous catecholamine administration is also possible. With hemodialysis, perindopril can be removed from the systemic circulation. In bradycardia resistant to therapy, it may be necessary to install an artificial pacemaker. The dynamic control of the general state, the concentration of creatinine and electrolytes in the blood plasma is necessary.

Amlodipine

Information on overdose with amlodipine is limited.

Symptoms: marked reduction in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (the risk of severe and persistent arterial hypotension, including the development of shock and death).

Treatment: gastric lavage, the appointment of Activated carbon (especially in the first 2 hours after an overdose), maintaining the function of the cardiovascular system, the elevated position of the lower extremities, control of the BCC and diuresis, symptomatic and supportive therapy. To restore vascular tone - the use of vasoconstrictor agents (in the absence of contraindications to their use); to eliminate the effects of calcium channel blockade, intravenous administration of Calcium gluconate solution. Hemodialysis is ineffective.

Interaction with other drugs

Perindopril

Simultaneous use is not recommended:

Potassium-sparing diuretics, potassium preparations or potassium-containing food salt substitutes: although the serum potassium content is within the normal range, hypercaliemia may occur in some patients with perindopril. Potassium-sparing diuretics (for example, spironolactone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes can lead to a significant increase in plasma potassium levels, and therefore their use at the same time as ACE inhibitors is not recommended. If simultaneous therapy is necessary (in the case of confirmed hypokalemia), care should be taken to regularly monitor the potassium content in the blood plasma and ECG parameters.

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

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

Simultaneous use requiring special care:

Nonsteroidal anti-inflammatory drugs (NSAIDs), including inhibitors of cyclooxygenase-2 (COX-2), Acetylsalicylic acid in high doses (more than 3 g / day) and non-selective NSAIDs : the use of NSAIDs can lead to a decrease in the diuretic, natriuretic and hypotensive action of ACE inhibitors. The simultaneous use of ACE inhibitors and NSAIDs can lead to a deterioration in renal function, including the development of acute renal failure and an increase in serum potassium, especially in patients with reduced kidney 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 carefully monitor renal function, both at the beginning of treatment and during treatment.

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

Simultaneous application requiring attention

Diuretics (thiazide and "loopbacks"): in patients taking diuretics, especially with excessive removal of fluids and / or electrolytes, a significant decrease in blood pressure may be observed at the beginning of the use of ACE inhibitors. The risk of arterial hypotension can be reduced by discontinuing the diuretic, by increasing fluid and / or salt intake before starting therapy, starting therapy with low doses of perindopril with their further gradual increase.

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

Gold preparations: in patients receiving simultaneous injection therapy with gold preparations (sodium aurothiomalate) and ACE inhibitors, including perindopril, nitrate-like reactions are rarely noted ("flushes" of blood to the skin of the face, nausea, vomiting, decrease in blood pressure).

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

Agents for general anesthesia: the simultaneous use of ACE inhibitors and agents for general anesthesia can lead to increased hypotensive effect.

Amlodipine

Simultaneous use is not recommended:

Dantrolene (intravenous administration): in animal experiments after the introduction of Verapamil and dantrolen (intravenously), cases of fatal ventricular fibrillation and cardiovascular insufficiency associated with hyperkalemia were observed. Given the risk of developing hyperkalemia, the simultaneous use of blockers of “slow” calcium channels should be avoided, including and amlodipine and dantrolene.

Simultaneous use requiring special care:

Inductors CYP3A4 (rifampicin, Hypericum perforatum drugs, anticonvulsants, such as Carbamazepine, phenobarbital, phenytoin, phosphenytoin, primidone): the plasma concentration of amlodipine may decrease as a result of an increase in its metabolism in the liver. Caution should be exercised with the simultaneous use of amlodipine and microsomal oxidation inducers and, if necessary, adjust the dose of amlodipine.

Strong and mild inhibitors of CYP3A4 isoenzyme (protease inhibitors, azole antifungals (itraconazole and ketoconazole), macrolides such as Erythromycin and Clarithromycin, verapamil and diltiazem): an increase in plasma concentration of amlodipine and an increased risk of side effects, especially in patients with elderly, may increase the risk of side effects, especially in patients with elderly people, and increase the risk of side effects, especially in patients with elderly people who are older. Care should be taken with simultaneous use and, if necessary, adjust the dose of amlodipine.

Simultaneous application requiring attention

The simultaneous use of beta-blockers (bisoprolol, metoprolol) and alpha- and beta-blocker Carvedilol,used in chronic heart failure (CHF): increases the risk of hypotension and worsening of CHF in patients with uncontrolled or latent CHF (increased inotropic effect). In addition, beta-blockers can reduce excessive reflex cardiac sympathetic activation against the background of concomitant CHF.

Other combinations:

In monotherapy, it is safe to use amlodipine simultaneously with thiazide diuretics, beta-blockers, ACE inhibitors, prolonged-action nitrates, Nitroglycerin (for sublingual use), Digoxin, Warfarin, Atorvastatin, Sildenafil, antacids (aluminum hydroxide colds, anhydrous, I amn’t, I’ll be used with anhydrodiamine, antacids (alumina colloid, allover), antacids (aluminum hydroxide), antifungal, warfarin, atorvastatin, sildenafil, antacids (aluminum hydroxide), and NSAIDs, antibiotics and hypoglycemic agents for oral administration.

There is no interaction of the following drugs with amlodipine:

- with simultaneous use of amlodipine and cimetidine pharmacokinetic parameters of amlodipine did not change;

- with simultaneous use of amlodipine and sildenafil, there is no marked increase in the hypotensive effect of each of the drugs;

- grapefruit juice: taking 240 ml of grapefruit juice 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: receiving repeated doses of amlodipine 10 mg in combination with atorvastatin at a dose of 80 mg does not lead to a significant change in the equilibrium pharmacokinetic parameters of atorvastatin;

- digoxin: simultaneous use of amlodipine and digoxin is not accompanied by a change in the concentration of digoxin in the blood serum and the renal clearance of digoxin in healthy volunteers;

- warfarin: in healthy male volunteers who took warfarin, the addition of amlodipine does not have a significant effect on the change in the index of prothrombin time due to warfarin;

- cyclosporine: amlodipine has no significant effect on the pharmacokinetic parameters of cyclosporine.

Dal'neva^®

Simultaneous application requiring special attention:

Baclofen: potentiation of hypotensive action is possible. It is necessary to control blood pressure and kidney function, as well as dose adjustment of amlodipine.

Simultaneous application requiring attention

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

Caution should be exercised when used with nitroglycerin, other nitrates or other vasodilators, since this may further decrease blood pressure.

Corticosteroids (mineral and glucocorticosteroids), tetracosactide: reduction of the hypotensive effect (fluid retention and sodium ions as a result of the action of corticosteroids).

Alpha-blockers (prazosin, alfuzosin, Doxazosin, Tamsulosin, terazosin):

increased hypotensive action and increased risk of orthostatic hypotension.

Amifostine: can potentiate the hypotensive effect of amlodipine.

Tricyclic antidepressants / neuroleptics / general anesthetics: increased hypotensive effect and increased risk of orthostatic hypotension.

special instructions

The special instructions relating to amlodipine and to perindopril are applicable to the drug Dalneva®.

Perindopril

Hypersensitivity / angioedema (angioedema)

When using ACE inhibitors, including perindopril, in rare instances, angioedema of the face, lips, tongue, vocal folds, and / or larynx may develop. With the appearance of these symptoms, the use of the drug Dalneva^® should be stopped immediately, the patient should be observed until the signs of edema disappear completely.

If angioedema affects only the face and lips, then its manifestations usually disappear on their own or antihistamines can be used to treat symptoms. Angioedema, accompanied by swelling of the tongue or larynx, can lead to airway obstruction and death.

If these symptoms appear, epinephrine (adrenaline) should be injected immediately subcutaneously at a dilution of 1: 1000 (0.3 or 0.5 ml) and / or ensure airway patency. The patient must be under medical supervision until the symptoms disappear completely and permanently.

In patients with a history of angioedema, not associated with the use of ACE inhibitors, the risk of its development can be increased during the use of drugs in this group.

In rare cases, the treatment with ACE inhibitors develops intestinal angioedema (angioedema). At the same time, patients have 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 C-1 esterase. The diagnosis is established using computed tomography of the abdominal cavity, ultrasound, or at the time of surgical intervention. Symptoms disappear after stopping the use of ACE inhibitors. In patients with abdominal pain, receiving ACE inhibitors, when conducting a differential diagnosis, it is necessary to consider the possibility of developing intestinal angioedema.

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 hymenoptera venom (Hymenoptera). ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. The use of an ACE inhibitor in patients receiving immunotherapy with hymenoptera poison should be avoided. However, the development of anaphylactoid reactions can be avoided by temporarily canceling the ACE inhibitor no less than 24 hours before the start of the desensitization procedure.

Anaphylactoid reactions during LDL apheresis using dextran sulfate

In rare cases, patients receiving ACE inhibitors may experience life-threatening anaphylactoid reactions when performing an apheresis of low-density lipoprotein (LDL) using dextran sulfate. To prevent an anaphylactoid reaction, discontinue therapy with an ACE inhibitor before treatment.