Curdaron ampoules. Medicinal reference Gootar

Date: 23.06.2020

This page has published detailed instructions for use. Cordaron. The available drug forms of the drug are listed (200 mg tablets, injections in ampoules for intravenous injections), as well as its analogues. Information on side effects that can cause Curdaron, about interaction with other drugs are presented. In addition to information about diseases, for the treatment and prevention of which the drug (arrhythmia, tachycardia, atrial and ventricular fibrillation) is prescribed, algorithms for reception, possible dosages for adults, in children, refineed the possibility of use during pregnancy and breastfeeding. Annotation to Cordaron is supplemented with recalls of patients and doctors. Composition of the drug.

Instructions for use and dosage

Pills

When prescribing the drug in the loading dose, various schemes can be used.

When applying in the hospital, the initial dose divided into several methods is from 600-800 mg per day to a maximum 1200 mg per day before reaching the total dose of 10 g (usually within 5-8 days).

With an outpatient application, the initial dose divided into several techniques is from 600 mg to 800 mg per day until the total dose of 10 g (usually within 10-14 days).

Supporting dose can vary in different patients from 100 mg per day to 400 mg per day. The minimum effective dose should be used in accordance with the individual therapeutic effect.

Because Amiodaron has a very long half-life, the drug can be taken every other day or take breaks at its reception 2 days a week.

The average therapeutic one-time dose is 200 mg. The average therapeutic daily dose is 400 mg.

Maximum single dose - 400 mg. Maximum daily dose - 1200 mg.

Ampoules

Curdaron for intravenous administration is intended for use in cases where the rapid achievement of the antiarrhythmic effect is required, or if it is impossible to use the drug inside.

With the exception of emergency clinical situations, the drug should be used only in the hospital in the intensive care unit under the permanent control of ECG and Hell.

When in / in the introduction, the cordaron cannot be mixed with other drugs or simultaneously enter other drugs through the same venous access. The drug should be administered only in a divided form. For dilution of cordaron, only a 5% dextrose solution (glucose) should be used. Due to the peculiarities of the drug form of the drug, it is not recommended to use the concentrations of an infusion solution that are less than those obtained during dilution of 2 ampoules in 500 ml of 5% dextrose (glucose).

To avoid reactions at the place of administration, the cordaron should be administered through the central venous catheter, with the exception of cardioreanimation cases during ventricular fibrillation, resistant to cardioversion, when, in the absence of central venous access, the drug can be administered into peripheral veins (the largest peripheral vein with maximum blood flow).

Heavy heart rate disorders, in cases where the reception of the N repair is not possible (except for cases of cardioreanimation when stopping the heart caused by ventricular fibrillation resistant to cardioversion)

The drug is introduced intravenously drip (dropper) through the central venous catheter.

The load dose is, as a rule, 5 mg / kg of body weight in 250 ml of 5% dextrose solution (glucose), administration is carried out for 20-120 minutes, if possible, using electronic pumps. This dose can be introduced re-2-3 times for 24 hours. The rate of administration of the drug is adjusted depending on the clinical effect. The therapeutic effect appears during the first minutes of administration and gradually decreases after the cessation of infusion, so if necessary, to continue the treatment of the injection form of cordaron, it is recommended to switch to a constant / in drip administration of the drug.

Supporting doses: 10-20 mg / kg / 24 h (usually 600-800 mg, but can be increased to 1200 mg for 24 hours) in 250 ml of 5% declaration solution (glucose) for several days. From the first day of infusion, a gradual transition should be started at the reception of cardarone inside at a dose of 600 mg (3 tablets) per day. The dose can be increased to 800-1000 mg (4-5 tablets) per day.

Cardioreanimation when stopping the heart caused by ventricular fibrillation resistant to cardioversion

The drug is injected intravenously inkjet. The first dose is 300 mg (or 5 mg / kg) in 20 ml of a 5% dextrose solution (glucose). If fibrigration is not fixed, it is possible to further administer the cordaron in / in the jet at a dose of 150 mg (or 2.5 mg / kg).

Structure

Amiodarone hydrochloride + excipients.

Forms of release

Tablets 200 mg.

Solution for intravenous administration (injections in ampoules for injection).

Cordaron - Antiarrhythmic drug. Amiodaron (active substance of the drug Curdaron) refers to class 3 (class of repolarization inhibitors) and has a unique mechanism of antiarrhythmic action, because In addition to the properties of Class 3 antiarrimics (blockade of potassium channels), it has the effects of class 1 antiarrimics (sodium blocking), class 4 antiarrimics (calcium channel blocks) and non-competitive beta-adrenobloculous effect.

In addition to antiarrhythmic effects, the drug has antianginal, coronary separating, alpha and beta-adrenoblocking effects.

The antiarrhythmic effect of the drug is due to the increase in the duration of the 3 phase of the potential of cardiomyocytes, mainly due to the blocking of ion current in potassium channels (the effect of class 3 antiarrimics according to the classification of Vogan-Williams); a decrease in the automatism of the sinus node, leading to a decrease in heart rate; non-competitive blockade of alpha and beta adrenoreceptors; the slowdown in the synoatrial, atrial and AV conduction, more pronounced during tachycardia; lack of changes in ventricular conductivity; an increase in refractory periods and a decrease in the causability of the myocardium atrial and ventricles, as well as an increase in the refractory period of the AV node; The slowdown in conducting and increasing the duration of the refractory period in additional AV bunches.

In addition, the cordarone has the following properties: the absence of a negative inotropic action when taken inward; reduction of oxygen consumption by myocardium due to a moderate decrease in OPS and CSS; an increase in the coronary blood flow due to direct impact on the smooth muscles of the coronary arteries; Maintaining heart emissions by reducing the pressure in the aorta and the reduction of the OPS; Effect on the exchange of thyroid hormones: inhibition of the conversion of T3 in T4 (chipoxin-5-periodinase block) and blocking the capture of these hormones with cardiocytes and hepatocytes, leading to the weakening of the stimulating effect of thyroid hormones on myocardium.

After the start of taking the drug inside, therapeutic effects are developing on average in a week (from several days to 2 weeks). After the cessation of its reception, amiodarone is determined in the blood plasma for 9 months. It should be taken into account the possibility of preserving the pharmacodynamic effect of amiodarone within 10-30 days after its cancellation.

Pharmacokinetics

Bioavailability after receiving inside among different patients ranges from 30% to 80% (the average value is about 50%). Amiodaron is characterized by slow flow in tissue and high affinity to them. During the first days of treatment, the drug accumulates in almost all tissues, especially in adipose tissue and except for it in the liver, lungs, spleen and cornea. Equilibrium state is achieved from 1 to several months, depending on the individual characteristics of the patient. The peculiarities of the pharmacokinetics of the drug explains the use of load doses, which is aimed at the rapid achievement of the necessary level of penetration into tissue, in which the therapeutic effect of amiodarone is manifested. Metabolized in the liver. The main metabolite - deethylamiodamon is pharmacologically active and can enhance the antiarrhythmic effect of the main compound. The removal of amiodarone begins in a few days. Displays mainly through the intestines.

Indications

Pills

Recognition prevention:

threatening life of ventricular arrhythmias and fibrillation of the ventricles of the heart (treatment should be started in the hospital with careful cardiomonitorization);
supported paroxysmal tachycardium, incl. documented attacks by recurrent sustained sustained paroxysmal tachycardia in patients with organic heart disease; documented attacks by recurrent sustained sustrodgery paroxysmal tachycardia in patients without organic heart diseases when antiarrhythmic drugs of other classes are not effective or there are contraindications to their use; documented attacks by recurrent sustainable sustaining paroxysmal tachycardia in patients with WPW syndrome;
clear arrhythmia (atrial fibrillation) and atrial trembles.

Prevention of sudden arrhythmic death in patients from high-risk group:

patients after a recently suffered myocardial infarction with more than 10 ventricular extrasystoles in 1 h, clinical manifestations of chronic heart failure and a reduced fraction of emission of left ventricle (<40%).

Solution

saving attacks of ventricular paroxysmal tachycardia;
the relief of the attacks of supertoday paroxysmal tachycardia with a high frequency of ventricular cuts (especially against the background of WPW syndrome);
reviving paroxysmal and stable shape of flickering arrhythmia (atrial fibrillation) and atrial trembles;
cardioreanimation when stopping the heart caused by ventricular fibrillation resistant to cardioversion.

Contraindications

SCSU (sinus bradycardia, synoyatrial blockade) except in cases of correction by an artificial rhythm driver (danger of a "stop" of a sinus node);
AV blockade 2 and 3 degrees in the absence of a permanent artificial rhythm driver (pacemaker);
two- and three perception blocks in the absence of a pacemaker;
hypokalemia, hypomagnemia;
interstitial lung diseases;
thyroid dysfunction (hypothyroidism, hyperthyroidism);
congenital or acquired elongation of the Qt interval;
the combination with drugs capable of lengthening the Qt interval and cause the development of paroxysmal tachycardius, including polymorphic ventricular tachycardia of the type "Piroet": antiarrhythmic agents of class 1 A (County, hydrochindin, dizopyramide, procainamide); Class 3 antiarrhythmic agents (dfethylide, ibortid, broth tosylate); Satolol; Others (non-antiarrhythmic) preparations, such as buredil; Vincamine; Some neuroleptics phenothiazine (chlorpromazine, tiraidazine, levomepromazine, thiuridazine, trifluorozine, fluufenazine), benzamide (amisulpride, sulctrid, sulpiride, thiaprid, veraryprid), butyrofenones (Droperidol, haloperidol), sintridol, pimozide; cisaprid; tricyclic antidepressants; antibiotics of groups of macrolides (in particular erythromycin with in / in administration, spiramichin); Azole; Anti-antimalarial means (chinin, chlorookhin, meflohin, halofintrine); Pentamidine in parenteral administration; dipemoanyl methylsulfate; Mizolastine; Asthemisol, Terfenadine; Fluoroquinolones;
children's and adolescent age up to 18 years old (efficiency and safety are not established);
pregnancy;
lactation period;
increased sensitivity to iodine and / or amiodar.

special instructions

The side effects of the cordaron are dose-dependent, therefore, to minimize the possibility of their occurrence, the drug should be used in a minimum effective dose.

Patients during treatment should avoid exposure to direct sunlight or take protective measures (for example, the use of sunscreen, wearing appropriate clothing).

Before receiving an amiodarone, it is recommended to conduct an ECG study and determining the level of potassium in the blood. Hypokalemia must be adjusted before the use of amiodarone. During treatment, it is necessary to regularly monitor the ECG (every 3 months), the level of hepatic transaminases and other liver function indicators.

In addition, due to the fact that the cordaron can cause hypothyroidism or hyperthyroidism, especially in patients with thyroid diseases in history, before taking amiodarone, a clinical and laboratory (TWG content) should be conducted to identify disorders of the function and diseases of the thyroid gland. During the treatment with amiodarone and within a few months after its termination, regular surveys require the identification of clinical or laboratory signs of changing the function of the thyroid gland. With suspected disruption of the function of the thyroid gland, it is necessary to determine the level of TSH in serum.

Regardless of the presence or absence during treatment with amodarons of pulmonary symptoms, it is recommended to conduct x-ray study of lungs and pulmonary functional samples.

Patients, long-term treatment for rhythm violations, reported cases of increasing the frequency of ventricular fibrillation and / or increasing the threshold of the pacemaker or an implanted defibrillator, which can reduce their effectiveness. Therefore, before starting or during treatment, the Cordaron should regularly check the correct functioning of these devices.

The appearance of shortness of breath or dry cough of both isolated and accompanied by the deterioration of the overall state, indicates the possibility of pulmonary toxicity, such as interstitial pneumatic treatment, suspicion of the development of which requires an x-ray study of light and pulmonary functional samples.

Due to the elongation of the ventricular repolarization period of the heart, the pharmacological effect of the Curdaron causes certain changes to the ECG: the elongation of the Qt interval, Qtc (corrected), possibly the appearance of waves U. It is permissible to increase the Qtc interval of no more than 450 ms or no more than 25% of the initial value. These changes are not a manifestation of the toxic effect of the drug, but require control to correct the dose and evaluation of the possible pro-athmogenic effect of cordaron.

With the development of AV blockade 2 and 3 degrees, synoatrial blockade or two-facility intraventricular blockade, treatment should be discontinued. In the event of AV blockade of 1 degree requires increased clinical control.

Although the occurrence of arrhythmia or exacerbation of the existing rhythm disorders was noted, the prohibition-generated amiodarone effect is weak, less than in most antiarrhythmic drugs, and is usually manifested in combination with some drugs or with violations of the electrolyte balance.

With vision vision or with a decrease in visual acuity, an ophthalmic survey must be carried out, including the inspection of the Eye DNA. With the development of neuropathy or neuritis of the optic nerve caused by amiodarone, the drug must be canceled due to the danger of the development of blindness.

Since the cordaron contains iodine, its reception can distort the results of the radioisotope of the thyroid gland, but does not affect the accuracy of determining the content of T3, T4 and TSH in blood plasma.

Before surgical intervention, an anesthesiologist's doctor should be informed that the patient receives the cordaron. Prolonged treatment with cardarone can enhance the hemodynamic risk inherent in local or general anesthesia. This is especially true of its bradycardic and hypotensive effects, reduced cardiac output and conductivity disorders.

In addition, in patients who received Curdaron, in rare cases immediately after surgery noted a sharp respiratory distress syndrome. With IVL, such patients require careful control.

Impact on the ability to driving vehicles and control mechanisms

During the treatment period, the Curdaron should refrain from driving a car and practicing potentially hazardous activities that require increased concentrations of attention and speed of psychomotor reactions.

Side effect

moderate dose-dependent bradycardia
violation of conductivity (synoyatrial blockade, AV blockade of various degrees)
arrhythmogenic action (there are reports on the occurrence of new arrhythmias or exacerbation of existing ones, in some cases - followed by a heart stop; these effects are observed mainly in cases of the use of carotron, together with drugs extending the QTC interval or with violations of the electrolyte balance; in the light of the available data it is impossible Determine whether the appearance of these rhythm violations is caused by cordaron, or is associated with the severity of cardiac pathology, or is a consequence of the ineffectiveness of treatment)
pronounced bradycardia or, in exceptional cases, stop the sinus node (mainly in patients with sinus node dysfunction and elderly patients)
progression of heart failure (with long-term use)
nausea, vomiting
reduced appetite
dulling or loss of taste
the feeling of gravity in the epigastrium (there is mainly at the beginning of treatment, pass after a dose reduction)
interstitial or alveolar pneumonite
reputing bronchiolitis with pneumonia (sometimes with death)
pleurisy
bronchospasm (in patients with severe respiratory failure, especially in patients with bronchial asthma)
acute respiratory distress syndrome (sometimes with death and sometimes immediately after surgery; it is possible to interact with high oxygen doses)
lonantic bleeding
microentes in corneal epitheliums consisting of complex lipids, including Lipofuscin
neurry optic nerve
hypothyroidism (increase in body weight, zrayafness, apathy, reduced activity, drowsiness, excessive compared to the expected action of amiodarone bradycardia)
hyperthyroidism, the appearance of which is possible during treatment and after it (cases of hyperthyroidism developed a few months after the abolition of amiodarone)
photosensitization
serious or bluish skin pigmentation (after the cessation of treatment, this pigmentation disappears slowly)
erythema (during radiation therapy)
skin rash (usually low-specific)
alopecia
exfoliative dermatitis (communication with the reception of the drug is not installed)
tremor or other extrapyramidal symptoms
violations of sleep
nightmarket dreams
mopathia
headache
thrombocytopenia, hemolytic anemia, aplastic anemia
vasculit
a few cases of impotence (communication with the drug is not installed).

Medicinal interaction

Contraindicated combinations

The use of carroton in combination therapy with preparations, which can cause polymorphic ventricular tachycardia type "Pirouette", because With their combination with amiodaron, the risk of developing this complication and fatal outcome increases:

antiarrhythmic agents: class 1A (County, hydrochindin, dyspeyramide, procainamide), class 3 (dfethylide, ibortid, broth tosylate), sotalol;
others (non-antiarrhythmic) preparations, such as buredil; Vincamine; Some neuroleptics: phenothiazines (chlorpromazine, ciamemazine, levomepromazine, thiuridazine, trifluoropezine, fluufenazine), benzamide (amisulpride, sulctrid, sulpirid, thiaprid, verarypride), butyrofenons (Droperidol, haloperidol), segindol, pimozide; tricyclic antidepressants; cisaprid; Macrolred antibiotics (erythromycin with in / in administration, spiramycin); Azole; Antimalarial means (chinin, chlorookhin, meflohin, halofantrine, lumefantrine); Pentamidine in parenteral administration; dipemoanyl methyl sulfate; Mizolastine; Asthemisol; Terfenadine; Fluoroquinolones (in particular Moxifloxacin).

with beta-adrenobloclars, with blocks of slow calcium channels, slowing the heart rate (verapamil, diltiaze), because There is a risk of developing disorders of automatic (severe bradycardia) and conductivity;
with laxative, stimulating intestinal peristalsis, which can cause hypokalemia, which increases the risk of development of ventricular tachycardia like "Pirouette". During treatment, the cores should apply the laxatives of other groups.

Combinations when applying caution

With preparations that can cause hypokalemia:

diuretics causing hypocalemia (in monotherapy or combination);
amphotericin in (in / c);
glucocorticosteroids (GKS) for systemic use;
tetracoactide.

The risk of developing ventricular violations of rhythm, especially ventricular tachycardia type "Pirouette" (hypokalemia is a predisposing factor). It is necessary to control the content of electrolytes in the blood, if necessary, the correction of hypokalemia, permanent clinical observation and ECG monitoring. In the case of the development of ventricular tachycardia of the type "Piroet", antiarrhythmic agents should not be used (ventricular pacemaker should be started, possibly in / in the introduction of magnesium salts).

With procanamide

Amiodaron can increase the plasma concentration of procanamide and its N-acetyl of procanamide metabolite, which can increase the risk of developing side effects of procanamide.

With anticoagulants indirect action

Amiodaron increases the concentration of warfarin by inhibiting the CYP2C9 isoenzyme. When combinations of warfarin with amiodaron, it is possible to enhance the effects of indirect anticoagulant, which increases the risk of bleeding. It follows more often to control the prothrombin time (MN) and correction of the dose of anticoagulant both during the treatment of amiodaries and after its cancellation.

With cardiac glycosides (drugs in anticipation)

There may be disorders of automatism (pronounced bradycardia) and atreservant conductivity. In addition, during a combination of digoxin with amiodaron, it is possible to increase the concentration of the digoxin in the blood plasma (due to the reduction of its clearance). Therefore, with a combination of digoxin with amiodaron, it is necessary to determine the concentration of digoxin in the blood and control the possible clinical and ECG manifestations of digitalistic intoxication. There may be reduced doses of digoxin.

With Esmolol

Disruptions of the contractility, automatism and conductivity (suppression of compensatory reactions of the sympathetic nervous system) are possible. Conduct clinical and ECG control.

With phenytino (and, extrapolation, with phosphenitium)

Amiodaron may increase the plasma concentrations of phenytoin due to the inhibition of the CYP2C9 isoenzyme, therefore, with a combination of phenytoin with amiodarone, the overdose of phenytown is possible, which can lead to the emergence of neurological symptoms; Clinical monitoring is needed and, at the very first signs of overdose, reduced dose of phenytoin, it is desirable to determine the concentration of phenytoin in the blood plasma.

With preparations metabolizing with the help of the CYP3A4 isoenzysis

With a combination of amiodarone, which is an inhibitor of CYP3A4 isoenzyme, with these drugs, it is possible to increase their plasma concentrations, which can lead to an increase in their toxicity and / or enhancing pharmacodynamic effects and may require a decrease in the dose of such drugs:

cyclosporin: It is possible to increase the concentration of cyclosporine in the blood plasma, associated with a decrease in the metabolism of the drug in the liver, which can increase the nephrotoxic effect of cyclosporine. It is necessary to determine the concentration of cyclosporine in the blood, the monitoring of the kidney function and the correction of the cyclosporine dosing mode during the treatment period of the amiodarone and after the discharge of the drug.

fentanyl: When combinations with amiodaron, fentanyl phantanyl pharmacodynamic effects are possible and improving the risk of developing its toxic effects.
other drugs, metabolizing with the participation of CYP3A4: Lidocaine (risk of sinus bradycardia and neurological symptoms), Tacrolimus (Risk of nephrotoxicity), Sildenafil (risk of increasing its side effects), Midazolas (Psychomotor Effects), Triazoles, Digidroergotamine, Ergotamine, Statins, Including Simvastatin (increasing the risk of muscle toxicity, rhabomyolysis, and therefore the dose of simvastatin should not exceed 20 mg per day, with its ineffectiveness, go to the reception of another statin, not metabolizing with CYP3A4).

With Orlistat

There is a risk of reducing the concentration of amiodarone and its active metabolite in the blood plasma. Clinical and, if necessary, ECG control.

With clonidine, guangafatin, cholinesterase inhibitors (subepezil, galantamine, rivastigmine, tarine, ambenonium chloride, pyridostigmine bromide, neostigmine bromide), pilocarpin

There is a risk of developing excessive bradycardia (cumulative effects).

With cimetidine, grapefruit juice

There is a slowdown in the amomiodarone metabolism and an increase in its plasma concentrations, it is possible to increase the pharmacodynamic and side effects of amyodaron.

With drugs for inhalation anesthesia

It has been reported the possibility of developing the following severe complications in patients receiving amiodarone, during anesthesia: bradycardia (resistant to the administration of atropine), arterial hypotension, conductivity disorders, reduction of cardiac output. Very rare cases of severe complications from the respiratory system (acute respiratory distress-syndrome of adults) were observed, sometimes fatal, which developed immediately after surgery, the occurrence of which binds to high oxygen concentrations.

With radioactive iodom

Amyodaron contains in its composition of iodine and therefore can disrupt the absorption of radioactive iodine, which can distort the results of the radioisotope of the thyroid gland.

With rifampicin

Rifampicin is a powerful inducer CYP3A4, so when co-use with amiodarone, a decrease in the plasma concentrations of amiodarone and deethylamiodarone is possible.

With the preparations of Zverboy

St. John's wort is a powerful Cyr3A4 inductor. In this connection, it is theoretically possible to reduce the plasma concentration of amiodarone and reduce its effect (there are no clinical data).

With HIV protease inhibitors (including Indinavir)

HIV protease inhibitors are Cyr3A4 inhibitors, so while simultaneous use with amiodarone can increase the concentration of amiodarone in the blood.

With clopidogrel

Clopidogrel, which is an inactive thienopyrimidine preparation, is metabolized in the liver with the formation of active metabolites. It is possible to interact between clopidogrel and amiodarone, which can lead to a decrease in the effectiveness of clopidogrel.

With dextromethorphan

Dextromethorphan is a CYP2D6 and CYP3A4 substrate. Amyodaron inhibits CYP2D6 and can theoretically increase the plasma concentration of dextromethorophane.

Analogs of the Medicinal Cordaron

Structural analogues for the acting substance:

Amiodaron;
Amicoordine;
Faith amiodar;
Cardiodaron;
Opakordin;
Rhythmodamine;
Sedaborron.

Analogs in the pharmacological group (antiarrhythmic drugs):

Adenocor;
Allapinin;
Asparks;
Bretlat;
Hypertonpalant (Gnafalin);
Dinkener;
Diphenin;
Cardiodaron;
Kinidin Duruless;
Lidocaine;
Moracisin;
Moullock;
Neo Hylitemal;
Nibentan;
Novocainamide;
Pamaton;
Panangin;
Prosanamide Esk;
Propanorm;
Conpaphenon;
Profession;
RitaMex;
Rhythmodamine;
Rhythmodan;
Rhymingmorm;
Seds;
Trimesine;
Etcisin;
Ethmosine.

Application in elderly patients

Caution should be used in elderly patients (high risk of developing pronounced bradycardia).

Application in children

Contraindicated children and adolescents under the age of 18 (effectiveness and safety are not established).

Application in pregnancy and breastfeeding

Curdaron is contraindicated in pregnancy and during lactation (breastfeeding).

Currently available clinical information is insufficient to determine the degree of risk of developing damages in the embryo when applying Curdaron in 1 trimester of pregnancy.

Since the thyroid gland of the fetus begins to bind iodine only from 14 weeks of pregnancy (amenorrhea), it is not expected to affect the amiodarone on it in the event of its earlier use. Excess iodine When using the drug after this period, it may lead to the appearance of laboratory symptoms of hypothyroidism in a newborn or even to the formation of a clinically significant goiter. Due to the effects of the drug on the thyroid gland of the fetal fetal, the cordaron is contraindicated for use during pregnancy, with the exception of special occasions of the presence of vital indications (with life-degrading ventricular violations of the heart rhythm).

active substance:amiodarone;

1 ml of solution contains 50 mg of amiodarone hydrochloride;

excipients: Alcohol benzyl, polysorbate 80, water for injection.

Dosage form

Injection.

Basic physico-chemical properties:transparent pale yellow liquid, practically free from suspended particles.

Pharmacotherapeutic group

Antiarrhythmic drugs III class. ATX code C01V D01.

Pharmacological properties

Pharmacodynamics.

Antiarrhythmic properties. An increase in the third phase of the action potential without influence on the level or frequency of the lift (class III according to the classification of Vaughan Williams). An isolated increase in the third phase of the action potential occurs due to a decrease in potassium current through the potassium channel, and no changes occur in the work of the sodium and calcium channel.

Slowing the heart rate by reducing the sinus node automatism. Atropine does not act as an antagonist of this action.

Non-competitively blocks alpha - and beta-adrenoreceptors.

Slows down the synoatrile, resort and nodal conductivity, which happens more intensively in the presence of a high frequency of heart abbreviations.

Does not affect ventricular conductivity.

Increases the refractor period and reduces the excitability of myocardium on a resort, assembly and ventricular level.

Slows down the conductivity and lengthens the refractory period of additional atrial and ventricular paths.

Negative inotropic effect is absent.

Cardiovary resuscitation in the event of a heart stopped, associated with ventricular fibrillation resistant to electrical thermal therapy.

The safety and effectiveness of intravenous administration of amiodarone patients who have occurred outside the hospital to stop the heart through ventricular fibrillation, resistant to electrical treatment therapy, was studied in two double-blind studies: the ARREST study in which amiodaron was compared with the placebo and the Alive study, in which amiodaron was compared with lidocaine.

The primary end point of both studies was the number of patients who survived by the time of hospitalization for inpatient treatment.

During the study of Arrest 504, patients who moved the heart stop outside the hospital due to the fibrillation of ventricles or ventricular tachycardia without a pulse, resistant to three and more defibrections and administration of adrenaline, were randomized in 2 groups, in one of which patients were rapidly injected into the peripheral vein of amiodar Dose of 300 mg, divorced in 20 ml of 5% glucose solution (246 patients), and in the other - placebo (258 patients). Amiodaron statistically significantly increased the chances of successful conducting resuscitation activities and hospitalization: among 197 patients (39%), which were alive at the time of delivery to the hospital, there were 44% of patients in the Amiodaron group compared with 34% of patients from the placebo group (P \u003d 0 03).

After the correction to other prognostic treatment factors of treatment, the adjusted odds ratio for the survival rate until the receipt of the amiodarone group compared with the placebo group was 1.6 (95% confidence interval: 1.1 - 2.4; p \u003d 0.02 ). In the Amiodaron group, compared with the placebo group, a higher frequency of arterial hypotension was observed (59% against 48%, p \u003d 0.04) and bradycardia (41% compared with 25%, p \u003d 0.004).

In the course of the study of Alive 347 patients with ventricular fibrillation, resistant to three or more defibrillations, the introduction of adrenaline and one more defibrillation, or with the recurrence of ventricular fibrillation after initially successful defibrillation were randomized to the ammiodarone group (at a dose of 5 mg / kg of the calculated body mass, 5% divided into 30 ml of glucose) and the corresponding placebo, which imitated lidocaine, or to a group of obtaining lidocaine (1.5 mg / kg at a concentration of 10 mg / ml) and the corresponding placebo, which simulated amiodaries and contained the same solvent (polysorbat 80).

Amiodaron statistically significantly increased the chances of successfully conducting resuscitation activities and hospitalization of 347 patients included in the study: 22.8% in the Amiodarone group (41 patients from 180) and 12% in the Lidocaine group (20 patients from 167), p \u003d 0.009. After amendments to other prognostic factors, which influenced the survival, the adjusted ratio of the chance for the survival rate until the receipt of the hospital for the amiodarone group compared to the Lidocaine group was 2.49 (95% confidence interval: 1.28 - 4.85; \u003d 0.007). There were no differences between two treatments regarding the number of patients who needed therapeutic measures about bradycardia using atropine or about low blood pressure using dopamine, as well as differences in relation to the number of patients who received lidocaine (in addition to the treatment appointed As part of the study). The number of patients who, after defibrillation and the introduction of the drug under study, arose a heart stop, in the Lidocaine group (28.9%), was statistically significantly more than in the amiodarone group (18.4%), p \u003d 0.04.

Pharmacokinetics.

The amount of intravenously introduced amiodarone in the blood is rapidly decreasing due to the saturation of tissues and receipt of it to the receptors. Maximum activity is achieved after 15 minutes and decreases within 4 hours.

Indications

Treatment with the drug should be started and, as a rule, monitor only in the hospital or under the supervision of a specialist. Curdaron ® for intravenous administration is intended only for the treatment of severe rhythm disorders that do not respond to other methods of treatment, or in the case when other treatments cannot be used.

Tahiaritimia associated with Wolf Parkinson-White syndrome.

Tahiaritimia of all types, including religative, nodal and ventricular tachycardia; atrial flirt and fibrillation; ventricular fibrillation; In the case when other drugs cannot be used.

Curdaron ® for intravenous administration can be used in the case when a quick response to treatment is required or when the drug is impossible.

Contraindications

Famous increased sensitivity to iodine, amiodarone or other components of the drug.

Sinus bradycardia, synocatrial blockade of the heart in the absence of an undocardial pacemaker (artificial rhythm driver).

Sinus node weak syndrome in the absence of an undocardial pacemaker (risk of a sinus node).

Violations of the atrioventricular conductivity of a high degree in the absence of an undocardial pacemaker.

Disrupting the function of the thyroid gland.

Vascular failure (vascular collapse).

Heavy arterial hypotension.

Children's age up to 3 years (presence in the composition of benzyl alcohol).

Pregnancy, except for exceptional circumstances.

Breastfeeding period.

Bifascicularity and trifascycular conductivity disorders, except when an endocardial cardiac card is installed, which operates constantly.

Intravenous administration of the drug is contraindicated in the case of arterial hypotension, severe respiratory failure, cardiomyopathy or heart failure.

Simultaneous use with drugs that can cause paroxysmal tachycardia type "Torsades de Pointes":

antiarrhythmic drugs of Class (County, hydrochindin, dizopyramide);
antiarrhythmic Class III preparations (Satolol, Dofethylide, Ibutilid);
other preparations, such as arsenic compounds, for example, bipridyl, cisapride, diphhemanyl, dischametron for intravenous administration, erythromycin for intravenous administration, misolastine, moxifloxacin, spiramsycin for intravenous administration, Vincamine for intravenous administration, TEMIFEN, Some neuroleptics (see "Interaction with other medicines and other types of interactions ").

These contraindications do not concern the use of amiodarone for cardiopulmonary resuscitation when the heart is stopped, which arose due to ventricular fibrillation and is resistant to external electrical therapy.

Interaction with other medicines and other types of interactions

Antiarrhythmic drugs. Many antiarrhythmic drugs oppress the heart automatism, the conductivity and the reduction of myocardium. The simultaneous use of antiarrhythmic agents, which belong to different classes, can ensure the achievement of a favorable therapeutic effect, but most often treatment with such a combination requires careful clinical monitoring and control of ECG. The simultaneous use of antiarrhythmic agents that can cause Torsade de Pointes type ventricular tachycardia (amiodar, dyspeciramide, quinidine compounds, sotalol, buredil and others), contraindicated.

The simultaneous use of antiarrhythmic agents of the same class is not recommended, except for exceptional cases, since such treatment increases the risk of side effects from the heart.

Simultaneous use with drugs that have a negative inotropic effect, contribute to the slowdown of cardiac rhythm and / or slow down atrioventricular conductivity, requires careful clinical monitoring and control of ECG.

Drugs that can cause paroxysmal ventricular tachycardia like "Torsade de Pointes". This serious type of arrhythmia can be caused by certain drugs regardless of whether they have an antiarrhythmic effect. The favorable factor is hypokalemia, as well as bradycardia or innate or acquired existing elongation of the Qt interval.

To medicines that can cause paroxysmal tachycardia type « torsade de Pointes, in particular, class III antiarrhythmic agents, class III and some neuroleptics. For erythromycin, spiramsycin and vinkamine, this interaction is realized only when using intravenous dosage forms.

The simultaneous use of two drugs, each of which contributes to the occurrence of ventricular tachycardia type « torsade de Pointes, usually contraindicated.

However, methadone and some subgroups of drugs is an exception to this rule:

Bradycardia funds Most medicines can cause bradycardia. This applies to, in particular, antiarrhythmic agents of the class IA, beta-blockers, some antiarrhythmic agents of class III, some calcium channel blockers, drugs, pylocarpine and anticholinesterase drugs.

The risk of developing pronounced bradycardia (additional effect).

These contraindications do not concern the use of amiodarone during cardiopulmonary resuscitation in the event of a heart stopped, associated with ventricular fibrillation, with the ineffectiveness of the external use of electric shock.

With cyclosporin.Increasing the concentration of cyclosporine in the blood due to the reduction of its metabolism in the liver with the risk of nephrotoxicity. Determination of the concentration of cyclosporine in the blood, the control of the function of the kidneys and the dose correction during the treatment of amiodarone.

Fluoroquinolones.During treatment with amiodarone, the use of fluoroquinolones should be avoided.

With the injecting form of diltiazem.

With an injection form of verapamil.Risk of bradycardia and atrioventricular blockade. If it is impossible to avoid the use of this combination, it is necessary to ensure a thorough clinical supervision and continuous monitoring of ECG indicators.

With neuroleptics that can cause paroxysmal ventricular tachycardia type "Torsade de Pointes":aMISULPRID, chlorpromazine, cyiamhazine, droperidol, fluufenazine, hanoperidol, levopromazine, pimozide, pipamperon, pipothiazine, sintridol, sulpride, sutridge, thiaprid, zucopentixol, thiuridazine, trifluorcezine, veraspride, fluufenazine. Increased risk of ventricular arrhythmias, in particular type « torsade de Pointes.

With methadone.Increased risk of ventricular arrhythmias, in particular type « torsade de Pointes. ECG control and clinical control are needed.

Combinations that require precautions during use

With anticoagulants for oral administration.Strengthening the action of anticoagulants and an increase in the risk of bleeding due to an increase in the level of anticoagulants in the blood plasma. It is necessary to control the level of prothrombin in the blood and control of the Ministry of Emergency Situations. An anticoagulant dose should be adjusted for oral administration both during the treatment with amiodarone and within 8 days after the cancellation of the drug.

With beta-blockers, except for sotalol (contraindicated combination).Violation of the contractile ability of the heart, automatism and conductivity (inhibition of compensatory sympathetic mechanisms). ECG control and clinical observation are required.

With beta-blockers in heart failure (Bisoprolol, Carvedilol, metoprolol, nebivolol).Disorders of automatic and conductivity of the heart with the risk of developing pronounced bradycardia. Increased risk of ventricular arrhythmia, in particular type « torsade de Pointes. Regular control of ECG and clinical observation is required.

With Dabigatran.Increased concentration of Dabigatran in blood plasma with increasing risk of bleeding. Clinical monitoring and adjustment of the dose of Dabigatran if necessary, but not higher than 150 mg / day. Since the amiodaron has a long half-life, then the emergence of interactions is possible within a few months after the cessation of the treatment with amiodar.

Substrates p-glycoprotein.Amyodaron is a p-glycoprotein inhibitor. It is expected that, while simultaneously use with substrates, p-glycoprotein will increase their concentration in the blood.

With drugs of vicecrow.Infertility of automatism (pronounced bradycardia) and impaired atrioventricular conduction. If digoxin is used, it increases its level in the blood due to the reduction of its clearance. ECG control and clinical monitoring are needed, controlling the level of digoxin in the blood and, if necessary, adjusting doses of digoxin.

With diltiazem for oral administration.The risk of bradycardia or an atrioventricular blockade, in particular among the elderly patients. ECG control and clinical observation are required.

With some macrolides (azithromycin, clarithromycin, roxitromycin). « torsade de Pointes. ECG control and clinical observation against the background of the simultaneous use of these drugs.

With verapamil for oral administration.Risk of bradycardia or atrioventricular blockade, especially in elderly patients. ECG control and clinical observation are required.

With means that can cause hypokalemia:diuretics (causing hypocalemia themselves or in combination with other drugs), stimulating agents, amphotericin in (for intravenous administration), glucocorticoids (for systemic use), tetracocalidide. Increased risk of ventricular arrhythmia, in particular type « torsade de Pointes "(hypokalemia is a favorable factor). Before appointing a medicinal product, it is necessary to adjust hypokalemia, and during treatment - ensure monitoring of ECG indicators, electrolyte content and clinical observation.

With lidocaine.The risk of increasing the concentration of lidocaine in the blood plasma, which can cause neurological and cardiological adverse reactions, through the oppression of the amiodarone of the metabolism of lidocaine in the liver. Clinical observation and control of ECG, if necessary, control the concentration of lidocaine in the blood plasma and adjustment of the dose of lidocaine during the treatment of amiodarone and after its cancellation.

With Orlistat.The risk of reducing the concentration of amiodarone and its active metabolites in the blood plasma. Clinical observation is needed and, if necessary, ECG.

With phenytino (by extrapolation - also with phosphenitoї).Increased phenytoin concentration in blood plasma with signs of overdose, especially neurological (decrease in phenytoin metabolism in the liver). Clinical observation and control of phgentine concentration in blood plasma and, possibly, dose correction is necessary.

With simvastatin.The increased risk of developing adverse reactions (depends on the concentration), such as rhabdomyolysis (due to the oppression of the metabolism of simvastatin in the liver, reduces cholesterol levels). Do not exceed a dose of simvastatin 20 mg per day. If this dose does not make it possible to achieve a therapeutic goal, you need to assign another statin that does not enter into this type of interaction.

With tacrolimus.Increasing the concentration of tacrolimus in the blood by oppressing its metabolism amiodar. It is necessary to determine the concentration of the tacrolimus in the blood, the control of the kidney function and the correction of the tacrolimus dose during simultaneous use with the amiodarone and after its cancellation.

Fleyhouse. Amiodaron increases the plasma concentration of the freakinide due to the inhibition of cytochrome CYP 2D6. Therefore, the freelide dose must be adjusted.

P450 3A4 cytochrome substrates. When such drugs are prescribed against the background of the use of amiodarone, which is a CYP 3A4 inhibitor, higher plasma concentrations of these drugs are possible, which can lead to an increase in their toxicity.

Fentanyl. The combination with amiodarone can determine the increase in pharmacological effects of fentanyl and increase the risk of its toxicity.

Statins.The risk of the toxicity of these drugs in relation to muscles increases, subject to the simultaneous purpose of the amiodarone with the statins, which are metabolized by CYP 3A4, such as Simvastatin, Atorvastatin and Lovastatin.

If necessary, the use of statins together with amiodaron is recommended to assign statins that are metabolized by CYP 3A4.

Other drugs that are metabolized under CYP3A4: Lidocaine, Tharolimus, Sildenafil, Triazola, Dihydroergotamine, Ergotamine, Colchicine.

Bradycardia funds.Increased risk of ventricular arrhythmia, in particular ventricular tachycardia type « torsade de Pointes. Clinical observation and ECG control.

CYP 2C9 substrates. Amiodaron increases the concentrations of substances that are CYP 2C9 substrates, such as warfarin or phenytoin, due to the oppression of the P450 2C9 cytochrome enzymes.

Combinations that require special attention.

With pilocarpine.The risk of excessive bradycardia (additive effects of bradycardia drugs).

Features of application

Caution relative to the method of application.

Infusion through central veins: severe rhythm disorders when the oral use of the drug is impossible, with the exception of cardiopulmonary resuscitation when the heart is stopped, which occurred due to ventricular fibrillation and is resistant to external electrical thermal therapy.

Injection amiodarons should be administered through the central veins, since the administration through peripheral veins can cause local reactions, such as surface veins flash. Injection amiodarone must be administered only in the form of infusion, since even a very slow injection of the drug may increase the manifestations of arterial hypotension, heart failure or severe respiratory failure (see section "Side reactions").

Cardiovary and pulmonary resuscitation when the heart is stopped, which arose due to ventricular fibrillation and is resistant to external electrical thermal therapy.

The introduction through peripheral veins is usually not recommended due to the risk of hemodynamic disorders (severe arterial hypotension, vascular failure). Infusion through central veins should always be applied when possible.

It is recommended to use the central venous catheter, subject to its availability. In another case, the drug can be administered through peripheral veins - the largest peripheral vein with maximum blood flow.

Do not mix with other drugs in one syringe.

It should be monitored as quickly as possible to monitor patients in the separation of intensive care with constant monitoring of blood pressure and ECG indicators.

If therapy amiodarone needs to continue, it is introduced as infusion through central veins with constant blood pressure monitoring and ECG.

Cardiac effects associated with the use of amiodarone. There were cases of a new or aggravation of the existing arrhythmia, which is amenable to treatment that were sometimes fatal (see the section "Adverse Reactions").

The amromethmogenic effect of amiodarone is weak or even less expressed than the arrhythmogenic effect of most antiarrhythmic drugs, and is usually manifested when applying certain combinations of drugs (see the section "Interaction with other drugs and other types of interactions") or with violations of electrolyte equilibrium.

The pulmonary effects associated with the use of amiodarone. There were several cases of interstitial pneumopathy when using injecting amiodarone. The appearance of shortness of breath or dry cough, both separately and on the background of the deterioration of the general condition, indicates the possibility of pulmonary toxicity, such as interstitial pneumatic, and requires control over the patient's condition through radiological examination methods (see section "Side Reactions"). It is necessary to revise the feasibility of using amiodarone, since interstitial pneumopathy is usually reversible under the condition of early cancellation of amiodarone.

In addition, in some patients treated with amiodarone, there were cases of acute respiratory distress syndrome immediately after surgery, therefore, during artificial ventilation of the lungs, it is recommended to carefully observe the condition of such patients.

The liver effects associated with the use of amiodarone. Within 24 hours after the start of the use of amiodarone for injecting administration, severe, and sometimes lethal hepatocellular failure can develop. At the beginning of treatment and later throughout the course of treatment with amiodarons, regular monitoring of the liver function is recommended (see the section "Side Reactions"). It is necessary to reduce the amiodarone dose or to cancel this drug if the transaminase levels increase more than three times compared with the normal values \u200b\u200bof these indicators.

Electrolyte Balance Disorders, especially Hypokalemia. It is important to take into account situations that can be associated with hypokalemia and can provoke pro-athmogenic effects. Hypokalemia should be eliminated to the use of amiodarone.

With the exception of emergency situations, injecting amiodarons should be used only in specialized departments of intensive therapy under the condition of continuous monitoring (ECG, blood pressure).

Anesthesia. Before surgical intervention, it is necessary to inform the anesthesiologist that the patient receives amiodaries.

Long-term treatment with amiodarone can increase the risk of developing hemodynamic side effects associated with general or local anesthesia, such as: bradycardia, arterial hypotension, a reduction in the percentage of cardiac output and conduction disorder.

Combinations (see section "Interaction with other drugs and other types of interactions") with beta-blockers, except for Satolol (contraindicated combination) and esmolol (a combination requires caution when applying), verapamil and diltiazem should be considered only to prevent ventricular arrhythmias threatening life, and for cardiopulmonary resuscitation when the heart is stopped due to ventricular fibrillation, which is resistant to external electrical thermal therapy.

Application during pregnancy or breastfeeding.

Pregnancy.Considering the effect of amiodarone on the thyroid gland of the fetus, this drug is contraindicated to use during pregnancy, except in cases where the use of its appointment exceeds the risk associated with it.

Lactation.Amiodaron and its metabolites together with iodine are excreted into breast milk in concentrations, higher than their concentration in the plasma of the woman. Through the risk of hypothyroidism in newborn breastfeeding is contraindicated during the treatment of amiodar.

The ability to influence the reaction rate when managing motor vehicles or other mechanisms. According to the safety of the use of amiodarone, there are no confirmations that amiodarone can affect the reaction rate when managing motor vehicles or other mechanisms.

Method of application and dose

Curdaron ® can be administered only on isotonic (5%) glucose solution.

Do not breed the drug isotonic sodium chloride solution, since the formation of a precipitate is possible!

Do not mix with other drugs in one infusion system.

Curdaron ® for intravenous administration should be applied only when there is the necessary equipment for monitoring cardiac function, defibrillation and pacemakers.

Curdaron ® for intravenous administration can be used before carrying out a direct current cardier.

The standard recommended dose of the drug is 5 mg / kg of body weight, which is injected by intravenous infusion over time from 20 minutes to 2 hours. The drug should be administered as a solution divorced in 250 ml of a 5% glucose solution. After that, repeated infusion of the drug in a dose of up to 1200 mg (approximately 15 mg / kg of body weight) can be used in a 5% glucose solution of up to 500 ml for 24 hours, while the infusion rate must be adjusted depending on the clinical response of the patient (see . section "Features of application").

In extremely urgent clinical situations, the drug, at the discretion of the doctor, can be introduced in the form of slow injection at a dose of 150-300 mg in 10-20 ml of a 5% glucose solution for at least 3 minutes. After that, the re-introduction of the drug can be carried out no earlier than in 15 minutes. For patients with which the CARDORON ® for intravenous administration is introduced in this way, it is necessary to carry out a thorough supervision - for example, in the intensive care unit (see the section "Features of application").

Translation from intravenous therapy with oral therapy. Immediately after receiving a response to treatment, it is necessary to simultaneously begin oral therapy with the drug in a conventional load dose (that is, 200 mg three times a day). After that, Curdaron ® for intravenous administration should be gradually canceled by a step-by-step dose reduction.

Pediatric population. The safety and efficacy of amiodarone in children are not defined. Due to the content of benzyl alcohol for intravenous administration, amiodaron is contraindicated in newborns, babies and children under 3 years old.

Elderly patients. Like all other patients, it is important to apply the minimum effective dose of the drug. Although evidence in favor of special requirements regarding the dosing of the drug in this group of patients are absent, these patients may be more prone to developing bradycardia and conduction disorders when applying too high dose. Special attention should be paid to monitoring the function of the thyroid gland (see the sections "Contraindications", "Features of Application" and "Side Reactions").

Cardiovascular Resuscitation. The recommended dose of the drug in the fibrillation of ventricular / ventricular tachycardia with the absence of a pulse resistant to defibrillation is 300 mg (or 5 mg / kg of body weight), injected in 20 ml of 5% glucose solution by quick injection. If ventricular fibrillation persists, you can apply intravenous administration of an additional 150 mg (or 2.5 mg / kg of body weight) of the preparation.

Children. The safety and efficacy of amiodarone for children today was not evaluated, so the use of this drug is not recommended for children. Amyiodarone ampoules for injection injection contains benzyl alcohol. There are reports of cases of death "shortness of shortness of shortness of breath" ("Hasping-syndrome", Gasping Syndrome) in newborns after intravenous administration of solutions that contain this preservative. The symptoms of this complication include the sudden appearance of shortness of breath, arterial hypotension, bradycardia and the development of the cardiovascular collapse.

Overdose

Information regarding the overdose of amiodarone during intravenous administration does not exist.

It is possible to occur sinus bradycardia, stopping heart, ventricular tachycardia, especially paroxysmal tachycardia type « torsade de Pointes, circulatory failure and liver damage.

Treatment should be symptomatic. Given the kinetic properties of the drug, it is recommended to control the heart function for a long time. Amiodaron and its metabolites are not subject to dialysis.

Adverse reactions

The adverse reactions are classified by classes of organ systems and the frequency of occurrence in accordance with the following criteria: very often (≥ 10%); Often (≥ 1%,< 10 %); нечасто (≥ 0,1 %; < 1 %); редко (≥ 0,01 %, < 0,1 %); редкие (< 0,01 %).

Violations of blood and lymphatic system.

In patients who accept amiodarons, the bone marrow granulomas accidentally discovered. The clinical significance of this is unknown.

Disturb from the heart.

Often:bradycardia.

Seldom:the occurrence of a new or worsening the flow of existing arrhythmia, sometimes with the subsequent heart stop. Pronounced bradycardia, stop of a sinus unit, requiring the abolition of amiodarone, especially in patients with sinus node dysfunction and / or elderly patients. Prohibition effect.

Frequency is not known: Paroxysmal ventricular tachycardia type « torsade de Pointes »

Disorders from the gastrointestinal tract.

Often:nausea.

Disruption of the general condition and reaction at the injection site.

Often:an inflammatory response is possible, in particular, the surface vein phlebitis, when administered directly to the peripheral vein; Reactions at the place of administration, including pain, erythema, edema, necrosis, Ecstava, formation of infiltrate, inflammation, skin induration, thrombophlebitis, cellulite, infection and pigmentation disorders.

Violations by the liver and biliary tract.

The lesion of the liver was diagnosed with elevated levels of transaminase in serum. The following side effects have been reported.

Seldom:usually moderate and isolated increase in transaminase level (1.5-3 times higher than the norm) at the beginning of the treatment, which disappeared after a decrease in the dose of the drug or even spontaneously; Acute liver damage with an increase in the level of transaminase in serum and / or jaundice, including liver failure, sometimes lethal, which requires the cancellation of the drug.

Violations by the immune system.

Seldom:hypersensitivity reactions, including anaphylactic shock.

Frequency unknown(Cannot be assessed by affordable data): There have been reported on cases of angioedema edema (swelling of Qink).

Endocrine disorders.

Often:in the absence of any clinical signs of the thyroid dysfunction, a certain "non-compliance" of the thyroid hormone levels (elevated level T4, a normal or somewhat reduced level of TC) does not require the abolition of the drug.

Often:hypothyroidism is manifested by classic symptoms of body weight, increased sensitivity to cold, apathy, drowsiness. A clearly expressed increase in TSH level confirms this diagnosis. The normal function of the thyroid gland is usually reduced gradually within 1-3 months after the cessation of treatment; The abolition of the drug is not necessary: \u200b\u200bif the use of amiodarone has reasonable indications, treatment can be continued in combination with replacement therapy of thyroid hormones using L-thyroxine, selecting a dose depending on the level of TSH.

Hyperthyroidism is much more difficult to diagnose, since its symptoms is less pronounced (a small unprecedented decrease in body weight, a decrease in the effectiveness of antiagonal and / or antiarrhythmic therapy). In elderly patients, mental symptoms or manifestations in the form of thyrotoxicosis may occur. The diagnosis is confirmed by a pronounced decrease in the level of highly sensitive TSH. In this case, the amiodarone should be canceled, after 3-4 weeks after which clinical recovery is usually begins. Potentially lethal serious cases require an urgent start of proper treatment.

If the cause for concern is thyrotoxicosis (both by itself and through its influence on the impressionable equilibrium of myocardium), then considering the non-permanent efficiency of antihyroid synthetic drugs can be unambiguously recommended treatment with high doses of corticosteroids (1 mg / kg) for a sufficiently long period (3 month). It has been reported on the cases of hyperthyroidism, which occurred for several months after the cancellation of amiodaron.

Violations from the nervous system.

Seldom:benign intracranial hypertension (pseudo-turn of the brain), headache.

Disorders from the respiratory system, chest and mediastinum.

Rare:acute respiratory distress syndrome, in some cases with fatal outcome, sometimes in the early postoperative period (interaction with high oxygen doses may be suspected). In the event of a side reaction, it should be given to the ability to cancel the amiodarone and find out the feasibility of the appointment of corticosteroids (see the section "Features of application"). Bronchospasm and / or apnea in case of severe respiratory failure, especially in patients with bronchial asthma. Interstitial pneumopathy.

Disorders from the skin and subcutaneous fiber.

Single:excessive sweating.

Frequency unknown:hives.

Violations from the vessels.

Often:usually moderate and short reduction in blood pressure. There were reports of cases of pronounced arterial hypotension or vascular collapse, in particular, in the event of an overdose or after too fast administration.

Seldom: Grinding heat.

Disorders from the musculoskeletal system and connective tissue.

Frequency unknown:backache.

Shelf life

Storage conditions

Keep out of the reach of children. Store in the original packaging at a temperature not higher than 25 ° C.

Incompatibility

Apply only permitted solvents (see section "Method of application and dose").

Packaging

№ 6: 3 ml in ampoule; 6 ampoules in polymer cells in a cardboard box.

Category of vacation

On prescription.

Manufacturer

Sanofi Vintor Industria, France.

The location of the manufacturer and its address of the activities of activity

1, Ru De La Virge Ambarage Lagrav 33565 - Carbon Blank Sedex, France.

The codeATX: C01BD01.

Pharmacological properties

Pharmacodynamics

Antiarrhythmic properties

Pediatric population

Pharmacokinetics

Pediatric population

Indications for use

Antiarrhythmic agents, class III. The codeATX: C01BD01.

Pharmacological properties

Pharmacodynamics

Antiarrhythmic properties

Increasing the duration of the 3rd phase of the potential of the heart of the heart cells, without changing its height or speed of its lifting (the effect of antiarrhythmics III class according to the classification of Viliams). An isolated increase in the duration of the 3rd phase of the action potential is the result of slowing potassium current without changing the sodium and calcium current. Bradycardic effect due to reduction of the sinus node automatism. This effect is not eliminated by the administration of atropine. Non-competitive blockade of alpha and beta adrenergic receptors. The slowdown in the synoatrial, atrial and atrioventricular conductivity, more pronounced during tachycardia. Does not change intraventricular conductivity. An increase in refractory periods and reducing the excitability of the myocardium atrial, ventricles, an atrioventricular node. Slowing and increase the duration of the refractory period in additional atrial and ventricular beams. Lack of negative inotropic action.

Cardiopulmonary resuscitation when stopping the heart caused by ventricular fibrillation, refractory to electrical thermal therapy

The efficiency and safety of intravenous administration of amiodarone patients with a heart stop, caused by ventricular fibrillation resistant to electrical thermal therapy, was estimated in two double-blind studies: ARREST study (comparison of amiodarone with placebo) and an alive study (comparison of amiodarone and lidocaine).

The primary end point of both studies was the number of patients living at the time of their arrival in the hospital.

In the study of the ARREST 504 of the patient with the secondary heart stop hospital after the fibrillation of ventricles or ventricular tachycardia without a stable pulse (at least 3 attempts to defibrillation and the use of adrenaline) were randomized into two groups and obtained either 300 mg of amiodaron, divorced in 20 ml of 5% Glucose solution and fast-entered peripheral vein (246 patients) or placebo (258 patients). In 197 patients (39%), alive when entering the hospital, amodarons significantly increased the likelihood of successful reanimation and hospitalization in the hospital: 44% in the amiodarone group and 34% in the placebo group (P \u003d 0.03).

After the correction to other prognostic factors, the adjusted ratio of the chance of survival after taking was 1.6 in the group of amiodarone compared to the placebo group (IC 95%, 1.1-2.4; p \u003d 0.02). In the Amiodaron group, compared with the placebo group, a larger number of patients showed hypotension (59% compared with 48%, p \u003d 0.04) or bradycardia (41% compared with 25%, p \u003d 0.004).

In the study of Alive 347 patients with ventricular fibrillation, resistant to three attempts of defibrillation, adrenaline, subsequent attempts to defibrillation, as well as patients with relapse after initially effective defibrillation, were randomized to groups of amiodarone admission (5 mg / kg of body weight, dilution of 30 ml 5 % glucose solution) and placebo lidocaine or in a group whose patients received lidocaine (1.5 mg / kg in a concentration of 10 mg / ml) and a placebo amiodarone containing the same solvent (polysorbate 80).

Among 347 patients involved in the study, amiodarone significantly increased the likelihood of reanimation and admission to the hospital: 22.8% in the Amiodaron group (41 patients from 180) and 12% in the lidocaine group (20 patients from 167), p \u003d 0.009. After amendments to other factors that could affect the probability of survival, the adjusted ratio of the chances of survival during hospitalization was 2.49 in patients receiving amiodarons (IC 95%: 1.28-4.85, p \u003d 0.007) compared with patients, obtained lidocaine. There was no difference between two treatment groups in relation to the number of patients who needed to relieve bradycardia atropine or blood pressure by dupamine, as well as in relation to the number of patients who received lidocaine (in addition to the drug, which was the subject of the study).

The number of patients with asistolis after defibrillation and the purpose of the treatment studied was significantly higher in the patients of the Lidocaine Group (28.9%), amiodarone (18.4%), p \u003d 0.04.

Pediatric population

Controlled clinical studies of use in children were not conducted. According to published studies, the portability of amiodarone was estimated at 1118 children with different degrees of arrhythmia.

The following doses were used in pediatric clinical trials:

Treatment of an attack: 5 mg / kg body weight for from 20 minutes to 2 hours. Supporting treatment: 10 -15 mg / kg / day from several hours to several days.

If necessary, take orally at a conventional loading dose on the first day of infusion.

Pharmacokinetics

After the administration of amiodarone, its concentration in the blood is very quickly reduced due to the admission of the drug in tissue; Activity reaches a maximum, approximately the 15th minute and disappears approximately 4 hours after administration.

Amyodaron is metabolized mainly with CYP3A4, as well as CYP2C8. Amiodaron and its metabolite, Deetylamiodamon, in vitro are potential cytochrome inhibitors CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP2D6, CYP2B6 and CYP2C8. Amiodaron and Deetylamiodrons can also inhibit transport proteins, such as p-glycoproteins and toast2 (organic cation transport protein). The study showed an increase of 1.1% concentration of creatinine substrate (toast2). In vivo data describes the interaction of amiodarone with CYP3A4, CYP2C9, CYP2D6 and P-glycoprotein substrates.

Pediatric population

Controlled clinical studies of the use of amiodarone in children were not conducted.

Preclinical Safety Data

In the course of 2-year studies of carcinogenicity on the rats, Amiodaron caused an increase in folicular thyroid tumors (adenoma and / or carcin) in the individuals of both sexes with clinically significant effects. Since the results of mutaging studies were negative, an epigenetic, not a gene toxic mechanism is assumed for this type of induction of tumors. Such an effect on the thyroid gland of rats and mice is most likely caused by the effect of amiodarone on the synthesis and / or release of the hormones of the thyroid gland. The significance of these results for people is low.

Contraindications

Antiarrhythmic agents, class III. The codeATX: C01BD01.

Pharmacological properties

Pharmacodynamics

Antiarrhythmic properties

Cardiopulmonary resuscitation when stopping the heart caused by ventricular fibrillation, refractory to electrical thermal therapy

The primary end point of both studies was the number of patients living at the time of their arrival in the hospital.

Pediatric population

Controlled clinical studies of use in children were not conducted. According to published studies, the portability of amiodarone was estimated at 1118 children with different degrees of arrhythmia.

The following doses were used in pediatric clinical trials:

Treatment of an attack: 5 mg / kg body weight for from 20 minutes to 2 hours. Supporting treatment: 10 -15 mg / kg / day from several hours to several days.

If necessary, take orally at a conventional loading dose on the first day of infusion.

Pharmacokinetics

Pediatric population

Controlled clinical studies of the use of amiodarone in children were not conducted.

Preclinical Safety Data

Side effect

Antiarrhythmic agents, class III. The codeATX: C01BD01.

Pharmacological properties

Pharmacodynamics

Antiarrhythmic properties

Cardiopulmonary resuscitation when stopping the heart caused by ventricular fibrillation, refractory to electrical thermal therapy

The primary end point of both studies was the number of patients living at the time of their arrival in the hospital.

Pediatric population

Controlled clinical studies of use in children were not conducted. According to published studies, the portability of amiodarone was estimated at 1118 children with different degrees of arrhythmia.

The following doses were used in pediatric clinical trials:

Treatment of an attack: 5 mg / kg body weight for from 20 minutes to 2 hours. Supporting treatment: 10 -15 mg / kg / day from several hours to several days.

If necessary, take orally at a conventional loading dose on the first day of infusion.

Pharmacokinetics

Pediatric population

Controlled clinical studies of the use of amiodarone in children were not conducted.

Preclinical Safety Data

Overdose

Antiarrhythmic agents, class III. The codeATX: C01BD01.

Pharmacological properties

Pharmacodynamics

Antiarrhythmic properties

Cardiopulmonary resuscitation when stopping the heart caused by ventricular fibrillation, refractory to electrical thermal therapy

The primary end point of both studies was the number of patients living at the time of their arrival in the hospital.

Pediatric population

Controlled clinical studies of use in children were not conducted. According to published studies, the portability of amiodarone was estimated at 1118 children with different degrees of arrhythmia.

The following doses were used in pediatric clinical trials:

Treatment of an attack: 5 mg / kg body weight for from 20 minutes to 2 hours. Supporting treatment: 10 -15 mg / kg / day from several hours to several days.

If necessary, take orally at a conventional loading dose on the first day of infusion.

Pharmacokinetics

Pediatric population

Controlled clinical studies of the use of amiodarone in children were not conducted.

Preclinical Safety Data

Precautions

Antiarrhythmic agents, class III. The codeATX: C01BD01.

Pharmacological properties

Pharmacodynamics

Antiarrhythmic properties

Cardiopulmonary resuscitation when stopping the heart caused by ventricular fibrillation, refractory to electrical thermal therapy

The primary end point of both studies was the number of patients living at the time of their arrival in the hospital.

Pediatric population

Controlled clinical studies of use in children were not conducted. According to published studies, the portability of amiodarone was estimated at 1118 children with different degrees of arrhythmia.

The following doses were used in pediatric clinical trials:

Treatment of an attack: 5 mg / kg body weight for from 20 minutes to 2 hours. Supporting treatment: 10 -15 mg / kg / day from several hours to several days.

If necessary, take orally at a conventional loading dose on the first day of infusion.

Pharmacokinetics

Pediatric population

Controlled clinical studies of the use of amiodarone in children were not conducted.

Preclinical Safety Data

Storage conditions

Antiarrhythmic agents, class III. The codeATX: C01BD01.

Pharmacological properties

Pharmacodynamics

Antiarrhythmic properties

Cardiopulmonary resuscitation when stopping the heart caused by ventricular fibrillation, refractory to electrical thermal therapy

The primary end point of both studies was the number of patients living at the time of their arrival in the hospital.

Pediatric population

Controlled clinical studies of use in children were not conducted. According to published studies, the portability of amiodarone was estimated at 1118 children with different degrees of arrhythmia.

The following doses were used in pediatric clinical trials:

Treatment of an attack: 5 mg / kg body weight for from 20 minutes to 2 hours. Supporting treatment: 10 -15 mg / kg / day from several hours to several days.

If necessary, take orally at a conventional loading dose on the first day of infusion.

Pharmacokinetics

Pediatric population

Controlled clinical studies of the use of amiodarone in children were not conducted.

Preclinical Safety Data

Dosage form: & nbspsolution for intravenous administration Structure:

In one ampoule contains:

Active substance
Amiodarone hydrochloride	150 mg
Excipients
Benzyl alcohol	60 mg
Polysorbat-80.	300 mg
Water for injections	up to 3.0 ml

Description:

Transparent solution of light yellow color.

Pharmacotherapeutic Group:antiarrhythmic ATH: & NBSP

C.01.B.D.01 Amiodaron

Pharmacodynamics:

Amiodaron refers to III class of antiarrhythmic drugs (the class of repolarization inhibitors) and has a unique antiarrhythmic action mechanism, since in addition to the properties of the class III antiarrimics (potassium channels), it has the effects of class I antiarrimics (blockade of sodium channels), class IV antiarrimics (calcium channel blockade ) and non-competitive beta-adrenoblocking effect.

In addition to antiarrhythmic action, it has an antiagonal, coronary-eyed, alpha and beta-adrenoblocking effects.

Antiarrhythmic properties:

increase duration of the 3rd phase of the action potential cardiomyocytes, mainly due to blocking ion current in potassium channels (effect of antiarrhythmic agent III classification of Williams);

reduction of the sinus node automatism, leading to a decrease in heart rate;

non-competitive blockade of alpha and beta adrenergic receptors;

slowing synoatrial, atrial and atrioventricularconductivity, more pronounced during tachycardia;

lack of changes in ventricular conductivity;

an increase in refractory periods and a decrease in the excitability of the myocardium atrial and ventricles, as well as an increase in the refractory period of an atrioventricular node;

slowing and increasing the duration of the refractory period in additional bunches of the atrocial ventricular conduct.

Other effects:

reducing oxygen consumption by myocardium due to a moderate decrease in total peripheral resistance and heart rate, as well as reduced myocardial reductions due to beta-adrenoblocking;

an increase in coronary blood flow due to direct impact on the tone of the coronary arteries;

preservation of cardiac output, despite some reduction in the reduction of myocardium, by reducing the total peripheral resistance and pressure in the aorta;

effect on the exchange of thyroid hormones: inhibition of the conversion of T3 in T4 (chipoxin-5-periodinase block) and blocking the capture of these hormones with cardiocytes and hepatocytes, leading to the weakening of the stimulating effect of thyroid hormones on myocardium.

restoration of cardiac activity when stopping the heart caused by fibrillation of ventricles resistant to defibrillation.

Pharmacokinetics:

With intravenous administration of the drug Cartardon®, its activity reaches a maximum after 15 minutes and disappears approximately 4 hours after administration. After the introduction of the amiodarone, its concentration in the blood is rapidly decreasing due to the admission of the drug in the tissue. In the absence of repeated injections, the drug is gradually displayed. With the resumption of its intravenous administration or when applying the drug, the inside is accumulated in the tissues. It has a large amount of distribution and can accumulate in almost all tissues, especially in adipose tissue and except for it in the liver, lungs, spleen and cornea. Communication with blood plasma proteins is 95% (62% with albumin, 33.5% - with beta-lipoproteins).

Amyodaron is metabolized in the liver using CYP3A4 and CYP2C8 isoenzymes. Its main metabolite deethylamiodamon is pharmacologically active and can enhance the antiarrhythmic effect of the main connection. And its active metabolite DeeTehylamiodamon in Vitro has the ability to inhibit Cyp1a1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP2A6, CYP2B6 and CYP2C8. And DeeThylamiodamon also demonstrated the ability to inhibit some conveyors such as p-glycoprotein (P-GP) and the carrier of organic cations (Pok2). In vivo was observed interaction of amiodarone with substrates of CYP3A4, CYP2C9, CYP2D6 and P-GP.

Basically excreted with bile and feces through the intestines. Amyodaron removal is very slow. And its metabolites are determined in the blood plasma for 9 months after the cessation of treatment.

Amiodaron and its metabolites are not subject to dialysis.

Indications:

Saving paroxysmal tachycardia seizures

- saving attacks of ventricular paroxysmal tachycardia;

- saving attacks of supertoday paroxysmal tachycardia with a high frequency of ventricular cuts, especially against the background of Wolf Parkinson-White's syndrome;

- the relief of paroxysmal and stable form of flickering arrhythmia (atrial fibrillation) and atrial trembles.

Cardioreanization when stopping the heart caused by fibrillation of ventricles resistant to defibrillation.

Contraindications:

Increased sensitivity to iodine, amiodarone or the auxiliary substances of the drug.

Sinus node weak syndrome (sinus bradycardia, synoyatrial blockade) in the absence of an artificial rhythm driver (pacemaker) (danger of a "stop" of the sinus node).

Atrioventricular blockade (II - III art.) In the absence of a permanent artificial driver of the rhythm (pacemaker).

Violations of intraventricular conductivity (two- and three-faculty blockades) in the absence of a permanent artificial frame of the rhythm (pacemaker). With such violations of conductivity, the use of the drug Curdaron® is intravenously possible only in specialized branches under the cover of a temporary rhythm driver (pacemaker).

The combination with drugs capable of lengthening the Qt interval and cause the development of paroxysmal tachycardius, including the ventricular "pyruette" tachycardia (see section "Interaction with other drugs"):

antiarrhythmic drugs: class IA (, hydrocheneroid, dyspeciramidproindine); antiarrhythmic drugs of class III (dfethylide, ibotid,); ; buredil;

other (non-antiarrhythmic) preparations such as; some neuroleptics of phenothiazines (, ciamemazin,), benzamide (, sulctrid, sulpride, verarypride), butyrofenones (, haloperidol), pimozide; cisaprid; tricyclic antidepressants; macrolide antibiotics (in particular with intravenous administration,); Azole; Antimalarial preparations (chinin, halofintrine); Pentamidine under parenteral importance; dipemoanyl methyl sulfate; Mizolastine; , terphelanadine; Fluoroquinolones.

The acquired elongation of the Qt interval is congenital.

Expressing blood pressure, collapse, cardiogenic shock.

Hypokalemia, hypomantey.

Thyroid dysfunction (hypothyroidism, hyperthyroidism).

Pregnancy (see section "Application during pregnancy and during breastfeeding").

The period of breastfeeding (see section "Application during pregnancy and during breastfeeding").

Age up to 18 years (efficiency and security are not established).

Intravenous inkjet administration is contraindicated in the case of arterial hypotension, severe respiratory failure, cardiomyopathy or heart failure (mighty of these states).

All of the above contraindications do not belong to the use of the drug Cordaron® during cardioreanimation when stopping a heart caused by ventricular fibrillation resistant to defibrillation.

Carefully:

With arterial hypotension, decompensated or severe(III - IV FC HSN by classificationNYHA) heart failure, severe respiratory failure, hepatic insufficiency, bronchial asthma, in elderly patients (high risk of developing severe bradycardia), with an atrioventricular blockade I degree.

Pregnancy and lactation:

Pregnancy

Currently available clinical information is insufficient to determine the possibility or inability to the occurrence of malformations in the embryo when using amiodarone in the first trimester of pregnancy.

Since the thyroid gland of the fetus begins to associate only from the 14th week of pregnancy (amenorrhea), it is not expected to affect the amiodarone on it in the case of its earlier use. Excess iodine When using the drug after this period, it may lead to the appearance of laboratory symptoms of hypothyroidism in a newborn or even to the formation of a clinically significant goiter.

Due to the effects of the drug on the thyroid gland of the fetus, contraindicated during pregnancy, with the exception of special cases, when the expected benefit exceeds the risks (with life-degrading ventricular heart rate violations).

Breastfall period

Amyodaron is distinguished in breast milk in significant quantities, so it is contraindicated during breastfeeding period (therefore during this period the drug should be canceled or stop breastfeeding).

Method of use and dose:

Curdaron® drug, an intravenous solution, is intended for use in cases where the rapid achievement of the antiarrhythmic effect is required, or if it is impossible to use the drug inside.

With the exception of emergency clinical situations, the drug should be applied only in the hospital in the intensive care unit under the constant control of the ECG and blood pressure!

With intravenous administration, the drug Cordaron® cannot be mixed with other drugs. Other drugs should not be introduced into the same line of the infusion system as the drug Cordaron®. Apply only in a divided form. For the dilution of the drug Kurdaron®, only a 5% solution of dextrose (glucose) should be applied. Due to the peculiarities of the drug form of the drug, it is not recommended to introduce an infusion solution with a concentration less than the concentration of the infusion solution obtained during dilution of 2 ampoules in 500 ml of 5% dextrose (glucose).

In order to avoid reactions at the place of administration, the drug Curdaron® should be administered through the central venous catheter, except in cases of cardioreanimation during ventricular fibrillation, resistant to defibrillation, when, in the absence of central venous access, it is possible to introduce a drug into peripheral veins (usually in the largest peripheral vein with maximum bloodstream) (see section "Special instructions").

Heavy heart rate disorders, in cases where the drug intake is impossible (except for cases of cardioreanimations when stopping the heart caused by fibrillation of ventricles resistant to defibrillation).

Intravenous drip administration through the central venous catheter

Typically, the load dose is 5 mg / kg of body weight in 250 ml of a 5% solution of dextrose (glucose) and is entered as possible using an electronic pump for 20-120 minutes. Intravenous drip administration can be repeated 2-3 times within 24 hours. The rate of administration of the drug is adjusted depending on the clinical effect. The therapeutic effect appears during the first minutes of administration and gradually decreases after the cessation of infusion, therefore, if necessary, to continue treatment with the CARDARON® drug, a solution for intravenous administration, it is recommended to switch to permanent intravenous drip injection of the drug. Supporting doses: 10-20 mg / kg / 24 hours (usually 600-800 mg, but can be increased to 1200 mg for 24 hours) in 250 ml of 5% declaration solution (glucose) for several days. From the first day of infusion, a gradual transition to the reception of the drug Curdaron® orally (3 tablets of 200 mg per day). The dose can be increased to 4 or even 5 tablets of 200 mg per day.

Intravenous inkjet administration

Intravenous jet maintenance is usually not recommended due to hemodynamic risk (a sharp decrease in blood pressure, collapse); Preferred is the infusion introduction of the drug, unless this is possible.

Intravenous inkjet administration should be carried out only in urgent cases in the ineffectiveness of other types of treatment and only in the separation of intensive therapy under constant monitoring of ECG, blood pressure.

The dose is 5 mg / kg body weight. Except for cases of cardioreanimation in fibrillation of ventricles resistant to defibrillation, intravenous jet administration of the drug Cordaron® should be carried out for at least 3 minutes. The re-administration of the drug Curdaron® should not be carried out earlier than 15 minutes after the first injection, even if the contents of only one ampoule (the possibility of the development of an irreversible collapse) was introduced at the first injection.

If there is a need to continue the introduction of the drug Cordaron®, it must be administered as an infusion. Cardioreanimation when stopping the heart caused by ventricular fibrillation resistant to defibrillation intravenous inkjet administration (see section "Special instructions")

The first dose is 300 mg (or 5 mg / kg of the drug Curdaron®) after dilution in a 20 ml of a 5% dextrose solution (glucose) and intravenously introduced.

If fibrillation does not stop, then additional intravenous jet administration of the drug CARDARON® in a dose of 150 mg (or 2.5 mg / kg) is possible.

Side effects:

The frequency of side effects was determined as follows: Very often (\u003e 10%), often (\u003e 1%,<10 %); нечасто (>0,1 %, <1 %); редко (>0,01 %, <0,1 %) и очень редко, включая отдельные сообщения (<0,01 %), частота неизвестна (по имеющимся данным частоту определить нельзя).

Cardiovascular disorders

Often : Bradycardia, usually moderate gentlemen of heart rate (heart rate). Reduced arterial pressure, usually moderate and transient. Cases of pronounced reduction in blood pressure or collapse were observed in overdose or too fast administration of the drug. Rarely: Arrhythmogenic action (there are reports on the occurrence of new arrhythmias, including ventricular "pyruete" tachycardia, or exacerbating existing, in some cases - followed by a heart stop), however, amidarone is less pronounced than most antiarrhythmic drugs. These effects are observed mainly in cases of the use of the drug Curdaron® in conjunction with drugs extending the period of repolarization of the ventricles of the heart (Qtc interval) or with violations of blood electrolytes in the blood (see "Interaction with other drugs"). Based on the available data, it is impossible to determine if the occurrence of these rhythm disorders was caused by the action of the drug Cordaron®, the severity of cardiovascular pathology or is a consequence of the ineffectiveness of treatment.

Pronounced bradycardia or, in exceptional cases, stopping the sine saw, requiring cessation of treatment with amiodarone, especially in patients with sinus node dysfunction and / or elderly patients.

The "rings" of blood to the skin cover, accompanied by a feeling of heat.

Unknown frequency: Ventricular "pyruette" tachycardia (see section "Interaction with other drugs", subsection "Pharmacodynamic interaction"; section "Special instructions").

Endocrine System Violations

Frequency unknown: hyperthyroidism.

Violations by the respiratory system, organs of the chest and mediastinum

Very rarely: cough, shortness of breath, interstitial pneumonitis (see "Special instructions"). Bronchospasm and / or apnea in patients with severe respiratory failure, especially in patients with bronchial asthma. Heavy respiratory complications (acute adult respiratory distress syndrome), sometimes with death (see the "Special Instructions" section).

Violations from the gastrointestinal tract

Very rarely: nausea.

Violations by the liver and biliary tract

Very rarely: an isolated increase in the activity of "liver" transaminase in serum, usually moderate (exceeding normal values \u200b\u200bby 1.5-3 times) at the beginning of treatment and decreases with a reduction in dose or even spontaneously. Acute liver damage (for the first 24 hours after intravenous administration of amiodarone) with an increase in the activity of "liver" transaminase and / or jaundice, including the development of hepatic insufficiency, sometimes fatal (see "Special Instructions").

Disturbing from the skin and subcutaneous fabrics

Very rarely: increased sweating. Unknown frequency: urticaria.

Nervous System Violations

Very rarely: benign intracranial hypertension (pseudo-turn of the brain), headache.

Impaired immune system

Very rarely: anaphylactic shock. Frequency unknown: angioedema edema (swelling of quinque).

Violations by skeletal and muscular and connective tissue

The frequency is unknown: pain in the lumbar and lumbosacral spine Common disorders and disorders at the injection site often: reactions at the injection site, such as pain, erythema, swelling, necrosis, extravagation, infiltration, inflammation, seal, thrombophlebitis, phlebitis, cellulite, infection, pigmentation.

Overdose:

Information on the overdose of the drug Cordaron®, the solution for intravenous administration is not. There is some information regarding the acute overdose of amiodarone, taken inside in tablets. It describes several cases of sinus bradycardia, stopping the hearts, seizures of ventricular tachycardia, paroxysmal ventricular "pyruete" tachycardia, circulatory disorders and liver functions, expressing blood pressure.

Treatment should be symptomatic (in bradycardia - the use of beta-adrenostimulantry the installation of the pacemaker, with ventricular "pyrutete" tachycardia - in / in the introduction of magnesium salts, rejuvenating pacemake). Nor nor its metabolites are removed during hemodialysis. No specific antidote.

Interaction:

Pharmacodynamic interaction

Preparations that can cause bidirectional ventricular "pyruette" tachycardia "or increase the duration of the Qt interval

Preparations that can cause ventricular "pyruette" tachycardia

Combined therapy with drugs that can cause ventricular "pyruette" tachycardia is contraindicated, since the risk of developing potentially lethal ventricular "pyruette" tachycardia is increasing.

Antiarrhythmic drugs: IA (, hydrochindin, dyspeyramide,), buredil.

Others (non-antiarrhythmic) drugs, such as; ; Some neuroleptics: phenothiazines (, cyamemazin,), benzamis (, sutridge, sulpride, veraspride), butyrofenons (,), pimozide; tricyclic antidepressants; cisaprid; Macrolred antibiotics (with intravenous administration,); Azole; Anti-reflective drugs (chinin, halofantrine, lumefantrine); Pentamidine in parenteral administration; dipemoanyl methyl sulfate; Mizolastine; ; Terfenadine.

Preparations that can increase the duration of the Qt interval

Aimiodarone sharing with drugs capable of increasing the duration of the Qt interval should be based on a thorough estimate for each patient the ratio of expected benefits and potential risk (the possibility of increasing the risk of development of ventricular "pyruette" tachycardia), when using such combinations, it is necessary to constantly monitor the ECG patients (to identify The elongation of the Qt interval), the content of potassium and magnesium in the blood.

In patients receiving, the use of fluoroquinolones should be avoided, including.

Preparations, powerful heart rate and disorders of automatic or conductivity combined therapy with these drugs is not recommended. Beta-adrenoblastors, "slow" calcium channels, CSS (,), can cause disorders of automatism (the development of excessive bradycardia) and conductivity.

Preparations that can cause hypokalemia

With laxative intestinal peristalsis, which can cause hypokalemia, which increases the risk of developing ventricular "pyruette" tachycardia. When combined with amiodaron, laxatives should be applied.

Combinations requiring caution when applying

With diuretics causing hypokalemia (in monotherapy or in combination with other drugs).

With systemic corticosteroids (glucocorticosteroids, mineral chiposteroids), tetracoactide.

With amphotericin in (intravenous administration).

It is necessary to prevent the development of hypoglycemia, and in the case of its occurrence to restore to the normal level, the potassium content in the blood is to control the concentration of electrolytes in the blood and ECG (for possible elongation of the Qt interval), and in the event of a ventricular "pyruette" tachycardia, antiarrhythmic drugs should not be used ( ventricular pacemutimulation should be launched; possible intravenous administration of magnesium salts).

Drugs for inhalation anesthesia

It has been reported on the possibility of developing the following severe complications in patients receiving, upon receipt of them with general anesthesia: bradycardia (resistant to the administration of atropine), arterial hypotension, conductivity disorders, reduction of cardiac output. Very rare cases of severe complications from the respiratory system, sometimes fatal (acute respiratory distress-syndrome of adults), which developed immediately after surgery, the occurrence of which is binding to high oxygen concentrations. Preparations that determine the heart rate (, cholinesterase inhibitors (, taper, ambenonia chloride, neostigmine bromide),)

The risk of developing excessive bradycardia (cumulative effects).

Effect of amiodarone on other drugs

Amiodaron and / or its metabolite DeeThylamiodamon inhibit CYP1A1, CYP1A2, CYP3A4, CYP2C9, CYP2D6, and P-GP isoenses and can increase the systemic exposure of drugs that are their substrates. Due to the prolonged period of the half-life of the amiodarone, this interaction may be observed even a few months after the cessation of its admission.

Medicinal preparations that are P-GP substrates

Amiodaron is a P-GP inhibitor. It is expected that its joint acceptance with drugs that are P-GP substrates will lead to an increase in the system exposure of the latter.

Heart glycosides (vintage drugs)

The possibility of disorders of automatic (severe bradycardia) and atreservant conductivity. In addition, during a combination of digoxin with amiodaron, it is possible to increase the concentration of the digoxin in the blood plasma (due to the reduction of its clearance). Therefore, with a combination of digoxin with amiodarone, it is necessary to determine the concentration of digoxin in the blood and control the possible electrocardiographic manifestations of digitalistic intoxication. There may be reduced doses of digoxin.

Dabigatran

Care should be exercised while simultaneously use of amiodarone with Dabigatran due to the risk of bleeding. A dose correction may be required in accordance with the instructions in its instructions.

Medicinal preparations that are the substrates of the CYP2C9 isoenzyme

Amiodaron increases the blood concentration of drugs, which are substrates of CYP2C9 isoenzyme, such as or by inhibiting cytochrome P450 2C9.

Warfarin

When combinations of warfarin with amiodaron, it is possible to enhance the effects of indirect anticoagulant, which increases the risk of bleeding. It follows more often to control the prothrombin time (MNA) and correction doses of indirect anticoagulants, both during the treatment with amiodarone and after the cessation of its reception.

Phenytoin

With a combination of phenytoin with amiodarone, the development of phenytoin overdose is possible, which can lead to the emergence of neurological symptoms; Clinical monitoring is needed and, at the very first signs of overdose, reduced dose of phenytoin, it is desirable to determine the concentration of phenytoin in the blood plasma.

Medicinal preparations that are substrates of the CYP2D6 isoenzyme

Flebunide

Amiodaron increases the plasma flexure concentration due to the inhibition of the CYP2D6 isoenzysis, and therefore the correction of the freaking doses is required.

Medicinal preparations that are substrates of the CYP3A4 isoenzyme

With a combination of amiodarone, the inhibitor of the CYP3A4 isoenzyme, with these drugs, it is possible to increase their plasma concentrations, which can lead to an increase in their toxicity and / or enhancing pharmacodynamic effects and may require reduction of their doses. Below are these drugs.

Cyclosporin

The combination of cyclosporine with amiodarone can increase the concentration of cyclosporine in the blood plasma, the dose correction of cyclosporine is necessary.

Fentanyl

The combination with amiodarone may increase the pharmacodynamic effects of fentanyl and increase the risk of developing its toxic effects. Inhibitors of the MMC-Coa-reductase (statins) (, and) increase in the risk of muscular toxicity of statins with simultaneous use with amiodaron. It is recommended to use statins that are not metabolized using the CYP3A4 isoenzyme.

Other drugs, metabolizing with the CYP3A4 isoenzyme: Fiscal development of sinus bradycardia and neurological symptoms), (risk of nephrotoxicity), (risk of increasing its side effects), (risk of psychomotor effects), triazola, dihydroergotamine, ergotamine,).

The drug, which is the substrate of CYP2D6 and CYP3A4 isoenzymes.

Dextromethorphan

Amiodaron inhibits CYP2D6 and CYP3A4 isoenzymes and can theoretically increase the plasma concentration of detertainment.

Clopidogrel

Clopidogrel, is an inactive thienopyrimidine drug, metabolizing in the liver with the formation of active metabolites. It is possible to interact between clopidogrel and amiodarone, which can lead to a decrease in the effectiveness of clopidogrel.

Effect of other drugs on amiodaron

Inhibitors of CYP3A4 and CYP2C8 isoenzymes may have the ability to inhibit amidarone metabolism and increase its blood concentration and, accordingly, enhance its pharmacodynamic and side effects.

It is recommended that the reception of the inhibitors of CYP3A4 isoenzyme inhibitors (for example, grapefruit juice and some drugs, such as, and HIV protease inhibitors (including amiodarone, HIV protease inhibitors are used with amiodarone concentration in the amiodarone. blood.

Inductors of CYP3A4 Isoenzyme

Rifampicin

Rifampicin is a strong inducer of the CYP3A4 isoenzyme, when used with amiodarone, it can reduce the plasma concentrations of amiodarone and deethylamiodarone.

Preparations of the Zverboy printed

St. John's wort is a strong inducer of the CYP3A4 isoenzyzerlet. In this connection, it is theoretically possible to reduce the plasma concentration of amiodarone and reduce its effect (there are no clinical data).

Special instructions:

With the exception of urgent cases, the intravenous administration of the drug Curdaron® should be carried out only in the intensive care unit with an ECG constant control (due to the possibility of bradycardia and arrhythmogenic action) and blood pressure (due to the possibility of reduced blood pressure).

It should be remembered that even with the slow intravenous jet introduction of the drug Kurdaron® it is possible to develop an excessive decrease in blood pressure, vascular collapse.

In order to avoid the occurrence of reactions at the place of administration (see the section "Sidey action"), the drug Curdaron®, a solution for intravenous administration, is recommended to be administered through the central venous catheter. Only in the case of cardioreanimation when the heart is stopped, caused by fibrillation of ventricles resistant to defibrillation, in the absence of central venous access (the absence of the established central venous catheter), the CARDARON® solution, a solution for intravenous administration, can be administered to a large peripheral vein with maximum blood flow.

If it is necessary to continue treatment with the drug Cordaron® after cardioreanimation, Curdaron® should be administered intravenously drip through the central venous catheter under constant control of blood pressure and ECG.

Cartardon® cannot be mixed in one syringe or dropper with other drugs. Other drugs should not be introduced into the same line of the infusion system as the drug Cordaron®.

Although the occurrence of arrhythmia or weighting of the existing rhythm disorders, sometimes fatal, the prohitmogenic effect of the drug Curdaron® is weakly pronounced, in comparison with the majority of antiarrhythmic drugs, and is usually manifested in the presence of factors that increase the duration of the Qt interval, such as interaction with other drugs and / / or impairment of electrolytes in the blood (see Sections "Side Effects" and "Interaction with Other Medicinal Products"). Despite the ability of the drug Cartaron® to increase the duration of the Qt interval, it showed low activity with respect to provoking ventricular "pyruette" tachycardia.

Due to the fact that it is possible to develop in very rare cases of interstitial pneumonitis after intravenous administration of the drug Curdaron®, with the appearance after its intravenous administration of severe shortness of breath or dry cough, both accompanied and not accompanied by a deterioration in general condition (increased fatigue, increasing body temperature ) It is required to conduct an x-ray of the chest and, if necessary, cancel the drug, since the interstitial pneumonite can lead to the development of pulmonary fibrosis. However, these phenomena are mainly reversible in the early abolition of the drug Corderon® using glucocorticosteroids or without applying them. Clinical manifestations usually disappear within 3-4 weeks. Restoration of the x-ray picture and the functions of the lungs occurs more slowly (in a few months). After the artificial ventilation of the lungs (for example, when bringing surgical interventions) in patients who were introduced CARDARON®, there were rare cases of the development of acute respiratory distress-syndrome of adults, sometimes with a fatal outcome (it is possible to interact with high oxygen doses in the breathing mixture) (see Section "Side Action"). Therefore, it is recommended to carry out strict control over the state of such patients. It is recommended to carefully monitor the functional "liver" tests (control of the activity of "liver transaminases" before the use of the drug Curdaron® and regularly during treatment with the drug. During the first 24 hours after intravenous administration of the drug Cordaron®, a solution for intravenous administration, an acute liver damage can develop (including hepatocellular insufficiency or hepatic failure, sometimes fatal) and chronic liver damage. Therefore, treatment with the drug Curdaron® should be discontinued when increasing the activity of "liver" transaminases, 3 times higher than the upper boundary of the norm.

Before the surgical intervention of an anesthesiologist, the patient adopts Cordaron®. Curdaron® treatment with the drug can enhance the hemodynamic risk inherent in local or general anesthesia. In particular, this refers to its bradycardic and hypotensive effects, reduced cardiac output and conductivity disorders.

It is not recommended simultaneous use with beta-adrenoblockers; CSS rejuving CSS blockers "slow" calcium channels (s); Laxative, stimulating intestinal peristalsis, which can cause the development of hypokalemia.

Disorders of the water and electrolyte balance, in particular hypokalemia: it is important to take into account situations that may be accompanied by hypokalemia, as predisposing to pro-amitimical phenomena. Hypokalemia should be adjusted before the use of the drug Cordaron®.

Before starting treatment with the drug, CARDARON® is recommended to register an ECG, and determine the content of serum potassium in serum and, if possible, determination of serum concentrations of thyroid hormones (T3, T4 and TSH).

The side effects of the drug (see the section "Sidey action") usually depend on the dose; Therefore, care should be taken when determining the minimum efficient supporting dose to avoid or reduce to a minimum of undesirable effects.

The Cartardon® drug may cause disorders of the thyroid function, especially in patients with impaired thyroid influence in its own or family history.

Therefore, in the case of a transition from the intravenous administration of the drug Kurdaron® on the reception of the drug Cordaron® inward, both during treatment, and a few months after the end of treatment, careful clinical and laboratory control of the function of the thyroid gland should be carried out. If the thyroid dysfunction is suspected, it is necessary to determine the concentration of TSH in the serum (with the help of supersensitive analysis on TSH).

In children, the safety and efficacy of the drug Cordaron® has not been studied. In the ampoules of the drug Cartardon®, a solution for intravenous administration, contains benzyl alcohol. Development has been reported in newborns with fatal death after intravenous administration of solutions containing benzyl alcohol. The symptoms of the development of this complication are: acute development of suffocation, decrease in blood pressure, bradycardia and collapse.

The drug Cartardon® contains in its composition and therefore can disrupt the absorption of radioactive iodine, which can distort the results of the radioisotope of the thyroid gland, but its use does not affect the accuracy of determining the content of T3, T4 and TSH in blood plasma.

Impact on the ability to control the transc. cf. And Meh.:

Based on the data on safety, there is no evidence that disrupts the ability to manage vehicles or engage in other potentially hazardous activities. However, as a precautionary measure, patients with paroxysmasms of severe rhythm disorders during the treatment of Curdaron® are desirable to refrain from managing vehicles and practicing potentially hazardous activities requiring increased concentration and speed of psychomotor, reactions.

Release form / Dosage:The solution for intravenous administration is 50 mg / ml. Packaging: 3 ml in ampoules of colorless glass (type I). 6 ampoules in plastic contour cellular packaging without coating (pallet). 1 pallet along with instructions for use in a cardboard pack. Storage conditions:

Store at a temperature not higher than 25 ° C.

Keep out of the reach of children.

Shelf life: 2 years. Do not use the drug after the expiration date indicated on the package. Conditions of vacation from pharmacies:On prescription Registration number:N014833 / 01 Registration date:27.01.2009 Registration Certificate Owner:Sanofi-Aventis France France Manufacturer: & NBSP Representation: & NBSPSanofi Russia, JSC Russia Date of updating information: & NBSP04,12.2014 Illustrated instructions

Antiarrhythmic drug

Active substance

Release form, composition and packaging

Introduction Solution Transparent, light yellow.

Auxiliary substances: benzyl alcohol - 60 mg, polysorbate 80 - 300 mg, water d / and - up to 3 ml.

3 ml - ampoules of colorless glass (type I) with a point of fault and two labeling rings on the top (6) - Packaging cell contour plastic (1) - Putures cardboard.

pharmachologic effect

Antiarrhythmic drug. Amiodaron refers to class III (the class of repolarization inhibitors) and has a unique antiarrhythmic action mechanism, since In addition to the properties of class III antiarrimics (blockade of potassium channels), it has the effects of class I antiarrimics (sodium channel blockade), class IV antiarrimics (calcium channel blockades) and non-competitive beta-adrenoblocking effect.

In addition to antiarrhythmic effects, the drug has antianginal, coronary separating, alpha and beta-adrenoblocking effects.

Antiarrhythmic action:

increased duration 3 phases of the potential of cardiomyocytes, mainly due to blocking ion current in potassium channels (the effect of class III antiarrimics according to Williams classification);
reducing the automatic sinus unit, leading to a decrease in heart rate;
non-competitive blockade of α- and β-adrenoreceptors;
slowing down the synoatrial, atrial and AV conductivity, more pronounced during tachycardia;
lack of changes in ventricular conductivity;
an increase in refractory periods and a decrease in the causability of the myocardium atrial and ventricles, as well as an increase in the refractory AV-node period;
slowing and increase the duration of the refractory period in additional AV bunches.

Other effects:

reducing oxygen consumption by myocardium due to a moderate decrease in OPS and CSS, as well as reduced myocardial reductions due to beta-adrenoblocking;
an increase in the coronary blood flow due to direct impact on the smooth muscles of the coronary arteries;
preservation of the emission, despite some decrease in the reduction of myocardium, by reducing the pressure in the aorta and the reduction of the OPS;
influence on the exchange of thyroid hormones: inhibition of the conversion of T3 in T4 (blockade of thyroxin-5-doniodinase) and blocking the capture of these hormones with cardiocytes and hepatocytes, leading to the weakening of the stimulating effect of thyroid hormones on myocardium;
restoration of cardiac activity when stopping the heart caused by ventricle fibrillation resistant to defibrillation.

When in / in the administration of the drug, its activity reaches a maximum after 15 minutes and disappears approximately 4 hours after administration.

Pharmacokinetics

Suction

After a / in the introduction of amiodarone, its concentration in the blood is quickly reduced due to the admission of the drug in the tissue. In the absence of repeated injections, amiodaries are gradually displayed. When renewed it in / in administration or when the drug is prescribed, the amiodaron is accumulated in the tissues.

Distribution

Printed binding is 95% (62% with albumin, 33.5% - with beta lipoproteins). Amiodarone has a large V D and can accumulate in almost all tissues, especially in adipose tissue and except for it in the liver, lungs, spleen and cornea.

Metabolism

Amyodaron is metabolized in the liver using CYP3A4 and CYP2C8 isoenzymes. Its main metabolite - deethylamiodamon is pharmacologically active and can enhance the antiarrhythmic effect of the main compound. Amiodaron and its active metabolite DeeTehylamiodamon in vitro have the ability to inhibit CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP2A6, CYP2B6 and CYP2C8 inhibitory. Amiodaron and DeeThylamiodamon also demonstrated the ability to inhibit some conveyors, such as P-GP and carrier of organic cations (Pok2). In vivo was observed interaction of amiodarone with substrates of CYP3A4, CYP2C9, CYP2D6 and P-GP.

Election

Basically excreted with bile and feces through the intestines. Amyodaron removal is very slow. Amiodaron and its metabolites are determined in the blood plasma for 9 months after the cessation of treatment.

Amiodaron and its metabolites are not subject to dialysis.

Indications

Saving attacks of paroxysmal tachycardia:

saving attacks of ventricular paroxysmal tachycardia;
saving attacks of supertoday paroxysmal tachycardia with a high frequency of ventricular cuts, especially against the background of Wolf Parkinson-White's syndrome;
the relief of paroxysmal and stable form of flickering arrhythmia (atrial fibrillation) and atrial trembles.

Cardioreanization when stopping the heart caused by fibrillation of ventricles resistant to defibrillation.

Contraindications

increased sensitivity to, amiodarone or the auxiliary substances of the drug;
SCSU (sinus bradycardia, synoyatrial blockade) in the absence of an artificial rhythm driver (pacemaker) (danger of a "stop" of a sinus node);
AV blockade II and III degree in the absence of a permanent artificial rhythm driver (pacemaker);
violations of intraventricular conductivity (two- and three-faculty blockades) in the absence of a permanent artificial rhythm driver (pacemaker). With such conductivity violations, the use of the drug Kurdaron in / in is possible only in specialized branches under the cover of the time driver of the rhythm (pacemaker);
hypokalemia, hypomagnemia;
pronounced arterial hypotension, collapse, cardiogenic shock;
thyroid dysfunction (hypothyroidism, hyperthyroidism);
congenital or acquired elongation of the Qt interval;
combination with drugs capable of lengthening the Qt interval and cause the development of paroxysmal tachycardium, including ventricular pyruette tachycardia: antiarrhemical preparations of class I (County, hydrochindin, dyspeyramide, procainamide); Class III antiarrhythmic agents (dfethylide, ibotid, broth tosylate); ; Others (non-antiarrhythmic) preparations, such as buredil; Vincamine; Some neuroleptics phenothiazine (chlorpromazine, tiraidazine, levomepromazine, thiuridazine, trifluorozine, fluufenazine), benzamide (amisulpride, sulctrid, sulpiride, thiaprid, veraryprid), butyrofenones (Droperidol, haloperidol), sintridol, pimozide; cisaprid; tricyclic antidepressants; antibiotics of groups of macrolides (in particular erythromycin with in / in administration, spiramichin); Azole; Antimalarial preparations (chinin, chlorookhin, meflohin, halofintrine); Pentamidine in parenteral administration; dipemoanyl methyl sulfate; Mizolastine; Asthemisol, Terfenadine; Fluoroquinolones;
pregnancy;
breastfeeding period;
age up to 18 years (efficiency and security are not established).

An intravenous-jet introduction is contraindicated in the case of arterial hypotension, severe respiratory failure, cardiomyopathy or heart failure (mighty of these states).

All of the above contraindications do not belong to the use of the drug Curdaron during cardioreanimation when stopping the heart caused by ventricular fibrillation resistant to defibrillation.

Carefully

With arterial hypotension, decompensated or severe (III-IV functional classes according to NYHA classification) heart failure, severe respiratory failure, hepatic insufficiency, bronchial asthma, in elderly patients (high risk of developing severe bradycardia), with AV degree AV-blockade.

Dosage

Curdaron for in / in administration is intended for use in cases where the rapid achievement of the antiarrhythmic effect is required, or if it is impossible to use the drug inside.

With the exception of emergency clinical situations, the drug should be used only in the hospital in the intensive care unit under the permanent control of ECG and Hell.

When in / in the introduction, the drug Cordaron cannot be mixed with other drugs. Other drugs should not be introduced into the same line of the infusion system as the drug Curdaron. Apply only in a divided form. For the dilution of the drug Cordaron, only a 5% dextrose solution (glucose) should be used. Due to the peculiarities of the drug form of the drug, it is not recommended to use the concentrations of an infusion solution less than those obtained during dilution of 2 ampoules in 500 ml of 5% dextrose (glucose).

To avoid reactions at the injection site, amiodarone should be administered through the central venous catheter, with the exception of cardioreanimation cases during ventricular fibrillation, resistant to defibrillation, when, in the absence of central venous access, peripheral veins (the largest peripheral vein with maximum blood flow can be used for the administration of the drug. ).

Heavy heart rate disorders, in cases where the drug is impossible inside (except for cases of cardioreanimation when the heart is stopped, caused by fibrillation of ventricles resistant to defibrillation)

Intravenous-drip administration through the central venous catheter

Typically, the load dose is 5 mg / kg of body weight in 250 ml of a 5% solution of dextrose (glucose) and is introduced as possible using electronic pumps for 20-120 minutes. An intravenous-drip administration can be repeated 2-3 times over 24 hours. The rate of administration of the drug is adjusted depending on the clinical effect. The therapeutic effect appears during the first minutes of administration and gradually decreases after the cessation of infusion, therefore, if necessary, to continue treatment with an injectionary preparation, Kardaron is recommended to move on permanent intravenous-drip administration of the drug.

Supporting doses: 10-20 mg / kg / 24 h (usually 600-800 mg, but can be increased to 1200 mg for 24 hours) in 250 ml of 5% declaration solution (glucose) for several days. From the first day of infusion, a gradual transition to the reception of the drug Curdaron inside (3 tabs is 200 mg / day). The dose can be increased to 4 or even 5 tab. 200 mg / day.

An intravenous-jet introduction should be carried out only in urgent cases in the ineffectiveness of other types of treatment and only in the separation of intensive therapy under constant monitoring ECG, blood pressure.

The dose is 5 mg / kg body weight. Except for cases of cardioreanimation with ventricular fibrillation, resistant to defibrillation, intravenous-jet administration of amiodarone should be carried out for at least 3 minutes. The re-administration of amiodarone should not be carried out earlier than 15 minutes after the first injection, even if the contents of only one ampoule (the possibility of the development of an irreversible collapse) was introduced at the first injection.

If there is a need to continue the introduction of amiodarone, it must be administered as an infusion.

Cardioreanimation when stopping the heart caused by ventricular fibrillation resistant to defibrillation

Intravenous

The first dose is 300 mg (or 5 mg / kg of the drug Cartardon) after dilution in 20 ml of a 5% dextrose solution (glucose) and intravenously entered.

If fibrigration is not fixed, then additional intravenous-jet administration of the drug Curdaron is possible at a dose of 150 mg (or 2.5 mg / kg).

Side effects

Determination of the frequency of adverse reactions: very often (≥10%); Often (≥1%,<10); нечасто (≥0.1%, <1%); редко (≥0.01%, <0.1%); очень редко, включая отдельные сообщения (<0.01%); частота неизвестна (по имеющимся данным частоту определить нельзя).

From the side of the cardiovascular system: Often - bradycardia (usually moderate gentleration of heart rate), decreased blood pressure, usually moderate and transient (cases of severe arterial hypotension or collapse were observed in overdose or too fast administration of the drug); Very rare - arrhythmogenic effect (/ there are reports of the occurrence of new arrhythmias, incl. Pyruet's ventricular tachycardia, or exacerbation of existing, in some cases - followed by a heart stop /, however, in amiodarone, it is less pronounced than most antiarrhythmic Preparations. These effects are observed mainly in cases of the use of the drug Cordaron together with drugs extending the period of repolarization of the ventricles of the heart / interval Qt C / or with violations of the electrolyte content in the blood. On the basis of the available data it is impossible to determine whether these rhythm disorders are caused by the action of the drug. CARDORDON, the severity of cardiac pathology or is a consequence of the ineffectiveness of treatment), expressed bradycardia or, in exceptional cases, stop the sinus unit, requiring cessation of treatment with amiodarone, especially in patients with sinus-node dysfunction and / or elderly patients), blood tides to the skin of the face; Unknown frequency - ventricular tachycardia like "Pirouette".

From the endocrine system: The frequency is unknown - hyperthyroidism.

From the respiratory system: Very rarely - cough, shortness of breath, interstitial pneumonite, bronchospasm and / or apnea (in patients with severe respiratory failure, especially in patients with bronchial asthma), acute respiratory distress syndrome (sometimes with fatal outcome).

From the digestive system:very rarely - nausea.

From the side of the liver and biliary tract: Very rarely - isolated increase in the activity of hepatic transaminases in serum (usually moderate, excess of normal values \u200b\u200b1.5-3 times, decreases with a decrease in dose or even spontaneously), acute liver damage (within 24 hours after the administration of amiodarone) with increasing transaminase and / or jaundice, including the development of hepatic insufficiency, sometimes with fatal outcome.

From the side of the skin and subcutaneous fabrics: very rarely - the feeling of heat, increased sweating; The frequency is unknown - urticaria.

From the nervous system: Very rare - benign intracranial hypertension (pseudo-turn of the brain), headache.

From the immune system: very rarely - anaphylactic shock; Unknown - angioedema edema (swelling of quinque).

On the side of the musculoskeletal system: The frequency is unknown - pain in the lumbar and lumbosacral spine.

Local reactions: Often - reactions at the place of administration, such as pain, erythema, edema, necrosis, extravagation, infiltration, inflammation, seal, thrombophlebitis, phlebitis, cellulite, infection, pigmentation.

Overdose

There is no information on overdose in amiodarone. There is some information regarding the acute overdose of amiodarone, taken inside in tablets. It describes several cases of sinus bradycardia, stopping the heart, seizures of ventricular tachycardia, paroxysmal ventricular tachycardia type "Pirouette", circulatory disorders and liver function, pronounced blood pressure.

Treatment It must be symptomatic (in bradycardia - the use of beta-adrenostimulants or installation of the pacemaker, with the ventricular tachycardia of the type "Pirouette" - in / in the introduction of magnesium salts, rejuvenating pacemake). Neither amiodarone nor its metabolites are removed during hemodialysis. No specific antidote.

Medicinal interaction

Preparations that can cause bidirectional ventricular tachycardia type "Piroet" or increase the duration of the Qt interval

Preparations capable of causing ventricular tachycardia like "Pirouette"

Combined therapy with drugs that can cause ventricular tachycardia like "Pirouette" is contraindicated, because The risk of developing potentially lethal ventricular tachycardia like "Pirouette" is increasing.

antiarrhythmic drugs: Class I A (County, hydrochindin, Dizeciramide, procainamide), Satolol, Buredil;
others (non-antiarrhythmic) drugs, such as; Vincamine; Some neuroleptics: phenothiazines (chlorpromazine, ciamemiazine, levomepromazine, thiuridazine, trifluopezine, fluufenazine), benzamide (amisulpride, sulctrid, sulpride, thiaprid, veraryprid), butyrofenons (Droperidol, haloperidol), sintridol, pimozide; tricyclic antidepressants; cisaprid; Macrolred antibiotics (erythromycin with in / in administration, spiramycin); Azole; illegal drugs (chinin, chlorookhin, mesflohin, halofintrine, lumefantrine); Pentamidine in parenteral administration; dipemoanyl methyl sulfate; Mizolastine; Asthemisol; Terfenadine.

Preparations that can increase the duration of the Qt interval

Sharing an amiodarone with drugs capable of increasing the duration of the Qt interval should be based on a thorough estimate for each patient the ratio of expected benefits and potential risk (the possibility of increasing the risk of risk of ventricular tachycardia type "Piroet"), when applying such combinations, it is necessary to constantly monitor the ECG patients (for Detecting the elongation of the Qt interval), the content of potassium and magnesium in the blood.

In patients taking amodarons, the use of fluoroquinolones, including moxifloxacin, should be avoided.

Preparations that reduce heart disease or causing disorders of automatic or conductivity

Combined therapy with these drugs is not recommended.

Beta-adrenobloclars, block plates of slow calcium channels, reduced heart rate (verapamil, diltiazem), can cause disorders of automatic (development of excessive bradycardia) and conductivity.

Preparations that can cause hypokalemia

with laxative, stimulating intestinal peristalsis, which can cause hypokalemia, which increases the risk of development of ventricular tachycardia type "PriUT". When combined with amiodaron, laxatives should be applied.

Combinations requiring caution when applying

with diuretics causing hypokalemia (in monotherapy or in combination with other drugs);
with systemic corticosteroids (glucocorticoids, mineralocorticoids), tetracactide;
with amphotericin in (in / in Introduction).

It is necessary to prevent the development of hypoglycemia, and in the case of its occurrence to restore to the normal level, the content of potassium in the blood, control the concentration of electrolytes in the blood and the ECG (for possible elongation of the Qt interval), and in the event of the occurrence of ventricular tachycardia type "Pirouet" should not be used antiarrhythmic drugs (ventricular pacemakers should be launched; possibly in / in the introduction of magnesium salts).

Drugs for inhalation anesthesia

It has been reported on the possibility of developing the following severe complications in patients receiving amiodaries, when they receive anesthesia: bradycardia (resistant to the administration of atropine), arterial hypotension, conductivity disorders, reduction of cardiac output.

Very rare cases of severe complications from the respiratory system, sometimes fatal (acute respiratory distress of adult syndrome), which developed immediately after surgery, the occurrence of which is associated with high oxygen concentrations.

Preparations, Cardiac Rhythm (Klonidin, Guangfatzin, Holinesterase Inhibitors (Donenezil, Galanamine, Rivastigmine, Tinner, Ambenonia Chloride, Neostigmin Bromide), Pilocarpine

The risk of developing excessive bradycardia (cumulative effects).

Effect of amiodarone on other drugs

Amiodaron and / or its metabolite DeeThylamiodaron inhibit CYP3A4, CYP2C9, CYP2D6 and P-glycoprotein isoenzymes and can increase the systemic exposure of drugs that are their substrates. Due to the term T 1/2 amiodarone, this interaction may occur even a few months after the cessation of its reception.

Medicinal preparations that are P-GP substrates

Amiodaron is a P-GP inhibitor. It is expected that its joint reception with drugs that are P-GP substrates will lead to an increase in the system exposure of the latter.

Heart glycosides (vintage drugs)

The possibility of disorders of automatic (severe bradycardia) and atreservant conductivity. In addition, during a combination of digoxin with amiodaron, it is possible to increase the concentration of the digoxin in the blood plasma (due to the reduction of its clearance). Therefore, with a combination of digoxin with amiodaron, it is necessary to determine the concentration of digoxin in the blood and control the possible clinical and electrocardiographic manifestations of digitalistic intoxication. There may be reduced doses of digoxin.

Dabigatran

Care should be exercised while simultaneously use of amiodarone with Dabigatran due to the risk of bleeding. A dose correction may be required in accordance with the instructions in its instructions.

Medicinal preparations that are the substrates of the CYP2C9 isoenzyme

Amiodaron increases the concentration in the blood of drugs, which are substrates of CYP2C9 isoenzyme, such as warfarin or phenytoin due to the inhibition of cytochrome P450 2c9.

Warfarin

When combinations of warfarin with amiodaron, it is possible to enhance the effects of indirect anticoagulant, which increases the risk of bleeding. It is necessary to control the prothrombin time (MHO) more often and correction of the doses of the anticoagulant, both during the treatment with amiodarone, and after the cessation of its reception.

Phenytoin

Medicinal preparations that are substrates of the CYP2D6 isoenzyme

Flebunide

Amyodaron increases the plasma concentration of freaking due to inhibition of the CYP2D6 isoenzysis. In connection with which the correction of the frecking doses is required.

Medicinal preparations that are substrates of the CYP3A4 isoenzyme

Cyclosporin

The combination of cyclosporine with amiodarone can increase the concentration of cyclosporine in the blood plasma, a dose correction is necessary.

Fentanyl

The combination with amiodarone may increase the pharmacodynamic effects of fentanyl and increase the risk of developing its toxic effects.

Inhibitors of the GMG-Coa RedChandase (Statins) (Simvastatin, Atorvastatin and Lovastatin)

An increase in the risk of muscular toxicity of statins with simultaneous use with amiodarone. It is recommended to use statins that are not metabolized using the CYP3A4 isoenzyme.

Other drugs metabolizing with CYP3A4 isoenzyme: lidocaine (risk of developing sinus bradycardia and neurological symptoms), tacrolimus (risk of nephrotoxicity), sildenafil (the risk of increasing its side effects) midazolam (risk of psychomotor effects), triazoles, Dihydroergotamine, Ergotamine, Colchicine.

The drug, which is the substrate of CYP2D6 and CYP3A4 - Dextromethorphan

Amiodaron inhibits CYP2D6 and CYP3A4 isoenzymes and can theoretically increase the plasma concentration of detertainment.

Clopidogrel

Clopidogrel, which is an inactive thienopyrimidine preparation, metabolizing in the liver to form active metabolites. It is possible to interact between clopidogrel and amiodarone, which can lead to a decrease in the effectiveness of clopidogrel.

Effect of other drugs on amiodaron

CYP3A4 and CYP2C8 isoenzyme inhibitors May have the potential to inhibit the metabolism of amiodarone and increasing its concentration in the blood and, accordingly, its pharmacodynamic and side effects.

It is recommended to avoid the reception of CYP3A4 inhibitors (for example, grapefruit juice and some drugs, such as cimetidine, and HIV protease inhibitors (including Indinavir) during amiodarone therapy. Inhibitors of HIV protease with simultaneous use with amiodarone can increase the concentration of amiodarone in the blood.

Inductors of CYP3A4 Isoenzyme

Rifampicin

Rifampicin is a powerful inducer of CYP3A4 isoenzyme, when used with amiodarone, it can reduce the plasma concentrations of amiodarone and deethylamiodarone.

Preparations of the Zverboy printed

St. John's wort is a powerful inducer of the CYP3A4 isoenzyzerlet. In this connection, it is theoretically possible to reduce the plasma concentration of amiodarone and reduce its effect (there are no clinical data).

special instructions

With the exception of urgent cases, the introduction of the drug Kurdaron should be carried out only in the intensive care unit with an ECG constant control (due to the possibility of developing bradycardia and arrhythmogenic action) and blood pressure (due to the possibility of decline in blood pressure).

It should be remembered that even with the slow intravenous-jet administration of the drug, Curdaron is possible to develop an excessive decrease in blood pressure, circulatory collapse.

In order to avoid the occurrence of reactions at the injection site injecting the injection form of the drug Cordaron, it is recommended to introduce through the central venous catheter. Only in the case of cardioreanimation when the heart stopped, caused by fibrillation of ventricles, resistant to defibrillation, in the absence of central venous access (the absence of the established central venous catheter), the injection form of the drug Curdaron can be administered to a large peripheral vein with maximum blood flow.

If it is necessary to continue treatment with the drug by the drug after cardioreanimation, the Curdaron should be administered intravenously through the central venous catheter under constant control of blood pressure and ECG.

Cordaron can not be mixed in one syringe or dropper with other drugs. Other drugs should not be introduced into the same line of the infusion system as the drug Curdaron.

Although the occurrence of arrhythmia or weighting of the existing rhythm disorders, sometimes fatal, the pro-athmogenic effect of amiodarone is weakly pronounced, in comparison with the majority of antiarrhythmic drugs, and is usually manifested in the context of factors that increase the duration of the Qt interval, such as interaction with other drugs and / or when Violations of blood electrolytes in the blood. Despite the ability of amiodarone to increase the duration of the Qt interval, amiodaron showed low activity with respect to provoking ventricular tachycardia type "Pirouette".

In connection with the possibility of development in very rare cases of interstitial pneumonitis after a / in the introduction of the drug Curdaron when the introduction of pronounced shorts or dry cough, both accompanied and not accompanied by a deterioration in the overall state (increased fatigue, temperature increase) is required Radiography of the chest and, if necessary, cancel the drug, because Interstitial pneumonite can lead to the development of pulmonary fibrosis. However, these phenomena are mainly reversible with early cancellation of amiodarone using GCS or without applying them. Clinical manifestations usually disappear within 3-4 weeks. Restoration of the x-ray picture and the functions of the lungs occurs more slowly (several months).

After artificial ventilation of the lungs (for example, when bringing surgical interventions) in patients who were injected by Curdaron, there were rare cases of the development of acute respiratory distress of adult syndrome, sometimes with a fatal outcome (it is possible to interact with high oxygen doses). Therefore, it is recommended to carry out strict monitoring of the state of such patients.

During the first day after the beginning of the use of the injection form of the drug, the cordaron can develop a heavy acute liver damage with the development of hepatic insufficiency sometimes with death. It is recommended to carefully monitor the functional hepatic tests (determining the activity of transaminase) before the reception of the drug Curdaron and regularly during the treatment with the preparation. Acute liver function may occur (including hepatocellular insufficiency or hepatic failure, sometimes fatal) and chronic liver damage during the first 24 hours after B / in the introduction of amiodarone. Therefore, the treatment of amiodarone should be discontinued with an increase in transaminase activity, 3 times higher than VGN.

Before the surgical intervention of the anesthesiologist's doctor should be informed that the patient receives the Cordarkon. Curdaron treatment with the drug can enhance the hemodynamic risk inherent in local or general anesthesia. In particular, this refers to its bradycardic and hypotensive effects, reduced cardiac output and conductivity disorders.

It is not recommended simultaneous use with beta-adrenoblockers; reduced CSS blockers of slow calcium channels (verapamil and diltiazem); Laxative, stimulating intestinal peristalsis, which can cause the development of hypokalemia.

Disorders of the electrolyte balance, in particular hypokalemia: it is important to take into account situations that may be accompanied by hypokalemia, as predisposing to pro-amitimical phenomena. Hypokalemia should be adjusted before the use of the drug Curdaron.

Before starting treatment with the drug, Cordaron is recommended to register an ECG, and determine the content of potassium in serum and, if possible, determination of serum concentrations of thyroid hormones (T3, T4 and TSH). The side effects of the drug usually depend on the dose; Therefore, care should be taken when determining the minimum efficient supporting dose to avoid or reduce to a minimum of undesirable effects.

Amyodaron can cause impaired thyroid function, especially in patients with impaired thyroid influence in its own or family history. Therefore, in the event of a transition to the reception of the drug, Curdaron inside during treatment and several months after the end of treatment, careful clinical and laboratory control should be carried out. If the thyroid dysfunction is suspected, it is necessary to determine the concentration of TSH in the serum (with the help of supersensitive analysis on TSH).

In children, the safety and efficacy of amiodarone was not studied. In the ampoules of the injectionary preparation, the cordaron contains benzyl alcohol. Development has been reported in newborns with fatal death after intravenous administration of solutions containing benzyl alcohol. The symptoms of the development of this complication are: acute development of suffocation, decrease in blood pressure, bradycardia and cardiovascular collapse.

Amiodarone contains in its composition of iodine and therefore can disrupt the absorption of radioactive iodine, which may distort the results of the radioisotope of the thyroid gland, but its use does not affect the reliability of determining the content of T3, T4 and TSH in blood plasma.

Impact on the ability to driving vehicles and control mechanisms

Based on the safety data, there is no evidence that amiodaron violates the ability to manage vehicles or engage in other potentially hazardous activities. However, as a precautionary measures, patients with paroxysms of severe rhythm disorders during the treatment of the drug, Kardaron, it is desirable to refrain from managing vehicles and potentially hazardous types of activities requiring increased concentration and speed of psychomotor reactions.

Pregnancy and lactation

Pregnancy

Currently available clinical information is insufficient to determine the possibility or inability to occur in the embryo development damages when using amiodarone in the first trimester of pregnancy.

Since the thyroid gland of the fetus begins to bind iodine only from the 14th week of pregnancy (amenorrhea), it is not expected to affect the amiodaron on it in the event of its earlier use. Excess iodine When using the drug after this period, it may lead to the appearance of laboratory symptoms of hypothyroidism in a newborn or even to the formation of a clinically significant goiter.

Due to the effects of the drug on the thyroid gland of the fetus, amiodaron is contraindicated during pregnancy, with the exception of special cases, when the expected benefit exceeds the risks (with life-degraded ventricular heart rate violations).

Breastfall period

Childcare

Contraindication: Children's and adolescent age up to 18 years old (efficiency and safety are not installed).

With violations of the kidney function

Minor removal of the drug with urine allows you to prescribe a drug in renal failure in medium doses. Amiodaron and its metabolites are not subject to dialysis.

When violations of the liver function

Caution is used with liver failure.

Application in old age

FROM caution It should be used in elderly patients (high risk of developing pronounced bradycardia).

Conditions of vacation from pharmacies

The drug is released by the prescription.

Terms and Storage Terms

The drug should be stored in an inaccessible place at temperatures not higher than 25 ° C. Shelf life - 2 years.