Cordarone - instructions for use, doses, side effects, contraindications

Amiodarone belongs to the third class of antiarrhythmic drugs (repolarization inhibitor class) and has a unique mechanism of antiarrhythmic action, in addition to the properties of class III antiarrhythmics (potassium channel blockade), it has the effects of class I antiarrhythmics (blockade of sodium channels), class IV antiarrhythmics (calcium channel blockade ) and non-competitive beta-adrenergic blocking action.

In addition to antiarrhythmic action, he has antianginal, coronary dilatory, alpha and beta adrenoblocking effects.

Antiarrhythmic properties:

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

a decrease in the automatism of the sinus node, which leads to a decrease in the heart rate;

non-competitive blockade of alpha- and beta-adrenergic receptors;

slowing of sinoatrial, atrial and atrioventricular conduction, more pronounced with tachycardia;

no changes in ventricular conduction;

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

slowing the conduction and prolongation of the refractory period in additional beams of the atrioventricular conduction.

Other effects:

reduction of oxygen consumption by myocardium due to a moderate decrease in the total peripheral resistance and heart rate, as well as a decrease in myocardial contractility due to beta-adrenergic blocking action;

increased coronary blood flow due to direct effects on the tone of the coronary arteries;

preservation of cardiac output, despite a slight decrease in myocardial contractility, by reducing the overall peripheral resistance and pressure in the aorta;

influence on the exchange of thyroid hormones: inhibition of the transformation of T3 to T4 (blockade of thyroxine-5-deiodinase) and blocking the seizure of these hormones by cardiocytes and hepatocytes, leading to a weakening of the stimulating effect of thyroid hormones on the myocardium.

restoration of cardiac activity in cardiac arrest caused by ventricular fibrillation, resistant to defibrillation.

Pharmacokinetics:

When administered intravenously, the drug Kordaron® its activity reaches a maximum after 15 minutes and disappears after about 4 hours after administration. After the administration of amiodarone, its concentration in the blood rapidly decreases due to the receipt of the drug in the tissue. In the absence of repeated injections, the drug is gradually eliminated. When resuming its intravenous administration or when the drug is administered orally amiodarone accumulates in the tissues. Amiodarone It has a large volume of distribution and may accumulate in almost all tissues, particularly in adipose tissue but her liver, lung, spleen, and cornea. The connection with plasma proteins is 95% (62% with albumin, 33.5% with beta-lipoproteins).

Amiodarone is metabolized in the liver with the help of isozymes CYP3A4 and CYP2C8. Its main metabolite, desethylamiodarone, is pharmacologically active and can enhance the antiarrhythmic effect of the basic compound. Amiodarone and its active metabolite dezetilamiodaron in vitro have the ability to inhibit isozymes CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP2A6, CYP2B6 and CYP2C8. Amiodarone and desethylamiodarone also demonstrated the ability to inhibit certain transporters, such as the P-glycoprotein (P-gp) and the organic cation carrier (PKK2). In vivo, the interaction of amiodarone with the substrates of the isoenzymes CYP3A4, CYP2C9, CYP2D6 and P-gp was observed.

It is mainly excreted with bile and feces through the intestine. Removal of amiodarone is very slow. Amiodarone and its metabolites are determined in blood plasma for 9 months after discontinuation of treatment.

Amiodarone and its metabolites are not dialyzed.

Indications:

- Curbing seizures of paroxysmal tachycardia

- relief of paroxysmal tachycardia;

- suppression of attacks of supraventricular paroxysmal tachycardia with a high incidence of ventricular contractions, especially against the background of Wolff-Parkinson-White syndrome;

- arresting a paroxysmal and stable form of atrial fibrillation (atrial fibrillation) and atrial flutter.

Cardioreanimation in case of cardiac arrest caused by ventricular fibrillation, resistant to defibrillation.

Contraindications:

Hypersensitivity to iodine, amiodarone or excipients of the drug.

Syndrome of weakness of the sinus node (sinus bradycardia, sinoatrial blockade) in the absence of an artificial pacemaker (pacemaker) (danger of "stopping" the sinus node).

Atrioventricular block (II-III st.) in the absence of a permanent artificial pacemaker (pacemaker).

Violations of intraventricular conduction (two- and three-beam blockades) in the absence of a permanent artificial pacemaker (pacemaker). With such conduction disorders, the use of Cordarone® is intravenously available only in specialized departments under the guise of a temporary rhythm pacemaker (pacemaker).

Combination with drugs that can prolong the QT interval and cause the development of paroxysmal tachycardias, including ventricular "pirouette" tachycardia (see section "Interaction with Other Drugs"):

antiarrhythmic drugs: IA class (quinidine, hydroquinidine, disopyramide procainamide); antiarrhythmic drugs of the III class (dofetilid, ibutilid, brethil tosylate); sotalol; beprideil;

other (non-antiarrhythmic) drugs such as wincamine; some neuroleptics of phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine trifluoperazine fluphenazine), benzamides (amisulpride, sultopride, sulpride, tiapride, verialpyride), butyrophenones (droperidol, haloperidol), sertindole, pimozide; cisapride; tricyclic antidepressants; macrolide antibiotics (in particular erythromycin with intravenous administration, spiramycin); azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine); pentamidine with parenteral administered; diphenamyl methyl sulfate; misolastine; astemizole, terfenadine; fluoroquinolones.

Congenital or the acquired QT interval elongation.

Expressive decrease in arterial pressure, collapse, cardiogenic shock.

Hypokalemia, hypomagnesemia.

Thyroid dysfunction (hypothyroidism, hyperthyroidism).

Pregnancy (see the section "Application during pregnancy and during lactation").

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

Age to 18 years (effectiveness and safety not established).

Intravenous fluid administration is contraindicated in the case of arterial hypotension, severe respiratory failure,cardiomyopathy or heart failure (possibly weighting these conditions).

All of the above contraindications do not apply to the use of Cordarone ® in cardiac recovery when cardiac arrest is caused by ventricular fibrillation, resistant to defibrillation.

Carefully:

With arterial hypotension, decompensated or severe (III-IV FC of CHF according to classification NYHA) heart failure, severe respiratory failure, liver failure, bronchial asthma, in elderly patients (high risk of severe bradycardia), with atrioventricular blockade of the I degree.

Pregnancy and lactation:

Pregnancy

Currently available clinical information is not sufficient to determine whether embryos can develop or develop in the first trimester of pregnancy.

Since the fetal thyroid begins to bind iodine only from the 14th week of pregnancy (amenorrhea), then it is not expected that amiodarone will affect it if it is used earlier.Excess iodine in the use of the drug after this period can lead to the appearance of laboratory symptoms of hypothyroidism in a newborn or even to the formation of a clinically significant goiter in it.

Due to the effect of the drug on the thyroid gland of the fetus, amiodarone contraindicated during pregnancy, except in special cases when the expected benefit exceeds the risk (with life-threatening ventricular arrhythmias).

Breastfeeding period

Amiodarone is excreted in breast milk in significant quantities, so it is contraindicated during breastfeeding (so during this period the drug should be canceled or stopped breastfeeding).

Dosing and Administration:

Kordarone ®, an intravenous solution, is intended for use in cases where a rapid antiarrhythmic effect is required, or when oral administration is not possible.

Except for urgent clinical situations, the drug should be used only in a hospital in an intensive care unit under constant ECG and blood pressure monitoring!

When administered intravenously, Cordarone® should not be mixed with other drugs. Do not inject other drugs into the same line of the infusion system as the Cordarone® preparation. Apply only in diluted form. To dilute Cordarone ®, only 5% dextrose (glucose) solution should be used. In connection with the characteristics of the drug form of the drug, it is not recommended to administer an infusion solution with a concentration lower than the concentration of the infusion solution obtained by diluting 2 ampules in 500 ml of 5% dextrose (glucose).

To avoid reactions at the site of administration, Cordarone® should be administered through a central venous catheter, except in cases of cardiac retention in fibrillation ventricles resistant to defibrillation, when, in the absence of central venous access, it is possible to inject the drug into the peripheral veins (usually the largest peripheral vein with the maximum blood flow) (see section "Special instructions").

Severe disturbances of the heart rhythm, in cases when it is impossible to take the drug inside (except for cases of cardiac retention in case of cardiac arrest caused by ventricular fibrillation, resistant to defibrillation).

Intravenous drip introduction through the central venous catheter

Usually the loading dose is 5 mg / kg of body weight in 250 ml of a 5% dextrose (glucose) solution and administered whenever possible by electronic pump for 20-120 minutes. The intravenous drip introduction can be repeated 2-3 times within 24 hours. The rate of administration of the drug is adjusted depending on the clinical effect. Therapeutic effect appears during the first minutes of administration and gradually decreases after the infusion has ceased, therefore, if it is necessary to continue treatment with Cordarone®, the solution for intravenous administration, it is recommended to switch to a permanent intravenous drip introduction of the drug. Maintenance 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% dextrose (glucose) solution for several days. From the first day of infusion, you should begin a gradual transition to taking Cordarone® inside (3 tablets of 200 mg per day). The dose can be increased to 4 or even 5 tablets of 200 mg per day.

Intravenous Injection

Intravenous fluid management is usually not recommended because of hemodynamic risk (a sharp drop in blood pressure, collapse); preferred is an infusion of the drug, if possible.

Intravenous fluid administration should be performed only in urgent cases with ineffectiveness of other types of treatment and only in the intensive care unit under constant monitoring of ECG, blood pressure.

The dose is 5 mg / kg body weight. With the exception of cases of cardiac resection with fibrillation ventricles resistant to defibrillation, intravenous fluid administration of Kordaron® should be performed for at least 3 minutes. Repeated administration of Cordarone® should not be performed earlier than 15 minutes after the first injection, even if the contents of only one ampoule (the possibility of irreversible collapse) were introduced at the first injection.

If there is a need to continue the administration of Cordarone®, it should be administered as an infusion. Cardiorescription at heart failure caused by ventricular fibrillation, resistant to defibrillation Intravenous jet injection (see section "Special instructions")

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

If fibrillation does not stop, then an additional intravenous fluid administration of Kordaron® at 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 (> 10%), often (> 1%, <10%); infrequently (> 0.1%, <1%); rarely (> 0.01%, <0.1%) and very rarely, including individual messages (<0.01%), the frequency is unknown (according to the available data, the frequency can not be determined).

Disorders from the cardiovascular system

Often: Bradycardia, usually a moderate decrease in heart rate (heart rate). Reduced blood pressure, usually mild and transient. Cases of marked reduction in blood pressure or collapse were observed in overdose or too rapid administration of the drug. Rarely: Arrhythmogenic action (there are reports of the occurrence of new arrhythmias, including ventricular "pirouette" tachycardia, or exacerbation of the existing ones, in some cases - followed by cardiac arrest), however, it is less expressed in amiodarone than in most antiarrhythmic drugs. These effects are observed mainly in cases of the use of Cordarone ® together with medicines,prolonging the period of repolarization of the ventricles of the heart (QTC interval) or in cases of disturbances in the electrolyte content in the blood (see "Interaction with other medicinal products"). Based on the available data, it is impossible to determine whether these rhythm disturbances are caused by the action of Cordarone®, the severity of the cardiovascular pathology, or is the result of ineffective treatment.

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

"Tides" of blood to the skin, accompanied by a feeling of heat.

Unknown frequency: Ventricular "pirouette" tachycardia (see section "Interaction with other medicinal products", subsection "Pharmacodynamic interaction", section "Special instructions").

Disorders from the endocrine system

Frequency unknown: Hyperthyroidism.

Disturbances from the respiratory system, chest and mediastinal organs

Very rarely: Cough, shortness of breath, interstitial pneumonitis (see section "Special instructions").Bronchospasm and / or apnea in patients with severe respiratory failure, especially in patients with bronchial asthma. Severe respiratory complications (acute respiratory distress syndrome of adults), sometimes fatal (see section "Special instructions").

Disorders from the gastrointestinal tract

Very rarely: Nausea.

Disturbances from the liver and bile ducts

Very rarely: Isolated increase in the activity of "hepatic" transaminases in the blood serum, usually moderate (exceeding normal values by 1.5-3 times) at the beginning of treatment and decreasing with decreasing dose or even spontaneously. Acute liver damage (within the first 24 hours after intravenous administration of amiodarone) with increased activity of "liver" transaminases and / or jaundice, including the development of liver failure, is sometimes fatal (see section "Special instructions").

Disturbances from the skin and subcutaneous tissues

Very rarely: Increased sweating. Unknown frequency: Hives.

Disturbances from the nervous system

Very rarely: Benign intracranial hypertension (pseudotumor of the brain), headache.

Immune system disorders

Very rare: Anaphylactic shock. Frequency unknown: Angioedema (edema of Quincke).

Disturbances from musculoskeletal and connective tissue

Frequency is unknown: Pain in lumbar and lumbosacral spine General disorders and disorders at injection site Frequently: Reactions at the site of administration such as pain, erythema, edema, necrosis, extravasation, infiltration, inflammation, compaction, thrombophlebitis, phlebitis, cellulitis, infection, pigmentation.

Overdose:

Information on the overdose of the drug Cordarone®, there is no solution for intravenous administration. There is some information regarding the acute overdose of amiodarone taken internally in tablets. Several cases of sinus bradycardia, cardiac arrest, attacks of ventricular tachycardia, paroxysmal ventricular "pirouette" tachycardia, disorders of blood circulation and liver function, expressed lowering blood pressure.

Treatment should be symptomatic (with bradycardia - the use of beta-adrenergic stimulants or installation of a pacemaker,with ventricular "pirouette" tachycardia - in / in the introduction of magnesium salts, pacing pacemaking). Neither amiodarone, nor its metabolites are removed during hemodialysis. There is no specific antidote.

Interaction:

Pharmacodynamic interaction

Drugs that can cause a bidirectional ventricular "pirouette" tachycardia "or increase the duration of the QT interval

Drugs that can cause ventricular "pirouette" tachycardia

Combination therapy with drugs that can cause the ventricular "pirouette" tachycardia is contraindicated, as the risk of developing a potentially lethal ventricular "pirouette" tachycardia increases.

- Antiarrhythmic drugs: IA (quinidine, hydroquinidine, disopyramide, procainamide), sotalol, beprideal.

- Other (non-antiarrhythmic) drugs, such as; wincamine; some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpride, tiapride, verialpyride), butyrophenones (droperidol, haloperidol), sertindole, pimozide; tricyclic antidepressants; cisapride; macrolide antibiotics (erythromycin with intravenous administration, spiramycin); azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine, lumefantrine); pentamidine with parenteral administration; diphenamyl methyl sulfate; misolastine; astemizole; terfenadine.

Drugs that can increase the duration of the QT interval

Joint use of amiodarone with drugs that can increase the duration of the QT interval should be based on a careful assessment of the ratio of expected benefit and potential risk for each patient (the possibility of an increased risk of developing a ventricular "pirouette" tachycardia), using such combinations it is necessary to constantly monitor the patient's ECG prolongation of the QT interval), the content of potassium and magnesium in the blood.

In patients receiving amiodarone, fluoroquinolones should be avoided, including moxifloxacin.

Drugs that reduce heart rate and cause disorders of automatism or conduction Combined therapy with these drugs is not recommended.Beta-adrenoblockers, blockers of "slow" calcium channels, decreasing heart rate (verapamil, diltiazem), can cause violations of automatism (the development of excessive bradycardia) and conduction.

Drugs that can cause hypokalemia

Unsupported combinations

- with a laxative, stimulating bowel movements, which can cause hypokalemia, which increases the risk of ventricular "the twisting 'tachycardia. When combined with amiodarone, laxatives of other groups should be used.

Combinations that require caution when applying

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

- C systemic corticosteroids (glucocorticosteroids, mineralokotikosteroidami) tetrakozaktidom.

- With amphotericin B (intravenous administration).

It is necessary to prevent the development of hypoglycemia, and in case of occurrence of restoring to the normal level of potassium in the blood, to control the concentration of electrolytes in blood and ECG (for possible lengthening QT interval), and should not in case of ventricular "the twisting" tachycardia applyantiarrhythmic drugs (ventricular pacing should be started, and intravenous magnesium salts may be injected).

Preparations for inhalation anesthesia

The possibility of developing the following serious complications in patients taking amiodarone, when they receive general anesthesia: bradycardia (resistant to atropine), arterial hypotension, conduction disorders, reduction in cardiac output. There were very rare cases of serious complications from the respiratory system, sometimes fatal (acute adult respiratory distress syndrome) which developed immediately after surgery, the occurrence of which is associated with high oxygen concentrations. Drugs that reduce heart rate (clonidine, guanfacine, cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, ambenonium chloride, pyridostigmine bromide, neostigmine bromide), pilocarpine)

The risk of developing excessive bradycardia (cumulative effects).

Influence of amiodarone on other drugs

Amiodarone and / or its metabolite, desethylamiodarone, inhibit the isoenzymes CYP1A1, CYP1A2, CYP3A4, CYP2C9, CYP2D6 and P-gp and may increase the systemic exposure of drugs that are their substrates.Due to the prolonged half-life of amiodarone, this interaction can be observed even a few months after discontinuation of its administration.

Drugs that are substrates of P-gp

Amiodarone is an inhibitor of P-gp. It is expected that his joint intake with drugs that are substrates of P-gp, will lead to an increase in the systemic exposure of the latter.

Cardiac glycosides (digitalis preparations)

The possibility of violations of automatism (pronounced bradycardia) and atrial-ventricular conduction. In addition, with the combination of digoxin with amiodarone, an increase in the concentration of digoxin in the blood plasma is possible (due to a decrease in its clearance). Therefore, when digoxin is combined with amiodarone, it is necessary to determine the concentration of digoxin in the blood and to monitor possible clinical and electrocardiographic manifestations of digitalis intoxication. You may need to reduce the dosage of digoxin.

Dabigatran

Caution should be exercised when using amiodarone with dabigatran at the same time because of the risk of bleeding.Dabigatran dose may need to be adjusted in accordance with the instructions in its instructions for use.

Drugs that are substrates of the isoenzyme CYP2C9

Amiodarone increases the concentration in the blood of preparations that are substrates of the isoenzyme CYP2C9, such as warfarin or phenytoin by inhibiting cytochrome P450 2C9.

Warfarin

When warfarin is combined with amiodarone, the effects of an indirect anticoagulant may increase, which increases the risk of bleeding. It should be more often monitored prothrombin time (INR) and corrected doses of indirect anticoagulants, both during treatment with amiodarone, and after discontinuation of its administration.

Phenytoin

When phenytoin is combined with amiodarone, an overdose of phenytoin may develop, which may lead to the appearance of neurologic symptoms; requires clinical monitoring and, at the first signs of an overdose, a decrease in the dose of phenytoin, it is desirable to determine the concentration of phenytoin in the blood plasma.

Drugs that are substrates of the isoenzyme CYP2D6

Flecainide

Amiodarone raises the plasma concentration of flecainide by inhibiting the isoenzyme CYP2D6, which requires the correction of doses of flecainide.

Drugs that are substrates of the isoenzyme CYP3A4

When combined with amiodarone, the inhibitor of the isoenzyme CYP3A4, these preparations can increase their plasma concentrations, which can lead to an increase in their toxicity and / or increased pharmacodynamic effects and may require a reduction in their doses. Below are listed such preparations.

Cyclosporin

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

Fentanyl

Combination with amiodarone may increase the pharmacodynamic effects of fentanyl and increase the risk of its toxic effects. Inhibitors of GMC-CoA reductase (statins) (simvastatin, atorvastatin and lovastatin) Increased risk of muscular toxicity of statins when used simultaneously with amiodarone. It is recommended to use statins that are not metabolized by the CYP3A4 isoenzyme.

Other drugs metabolized by the isoenzyme CYP3A4: lidocaine fisk development of sinus bradycardia and neurologic symptoms), tacrolimus (risk of nephrotoxicity), sildenafil (the risk of increasing its side effects), midazolam (risk of development of psychomotor effects), triazolam, dihydroergotamine, ergotamine, colchicine).

A medicinal preparation that is a substrate of the isoenzymes CYP2D6 and CYP3A4.

Dextromethorphan

Amiodarone inhibits the isoenzymes CYP2D6 and CYP3A4 and can theoretically increase the plasma concentration of dextromethorphan.

Clopidogrel

Clopidogrel, is an inactive thienopyrimidine drug metabolized in the liver with the formation of active metabolites. Possible interaction between clopidogrel and amiodarone, which can lead to a decrease in the effectiveness of clopidogrel.

The effect of other drugs on amiodarone

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

It is recommended to avoid taking inhibitors of the isoenzyme CYP3A4 (for example, grapefruit juice and certain medications such as cimetidine, and HIV protease inhibitors (incl. indinavir) during therapy with amiodarone.HIV protease inhibitors, when used simultaneously with amiodarone, can increase the concentration of amiodarone in the blood.

Inductors of the isoenzyme CYP3A4

Rifampicin

Rifampicin is a potent inducer of isoenzyme CYP3A4, when combined with amiodarone it can reduce the plasma concentration of amiodarone and dezetilamiodarona.

Preparations of St. John's Wort

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

Special instructions:

Except in urgent cases, intravenous administration of Cordarone® should be performed only in the intensive care unit with constant monitoring of the ECG (due to the possibility of bradycardia and arrhythmogenic action) and blood pressure (due to the possibility of lowering blood pressure).

It should be remembered that even with a slow intravenous injection of Kordaron®, it is possible to develop an excessive decrease in blood pressure, vascular collapse.

In order to avoid the occurrence of reactions at the site of administration (see the "Side effect" section), Cordarone®, an intravenous solution, is recommended to be administered through a central venous catheter. Only in the case of cardiac retention in the case of cardiac arrest caused by ventricular fibrillation resistant to defibrillation, in the absence of central venous access (absence of a central venous catheter), Cordarone®, an intravenous solution, can be injected into a large peripheral vein with maximum blood flow.

If it is necessary to continue treatment with Cordarone® after cardiac recovery, Cordarone® should be injected intravenously via a central venous catheter under the constant monitoring of blood pressure and ECG.

Cordarone® can not be mixed in one syringe or dropper with other medications. Do not inject other drugs into the same line of the infusion system as the Cordarone® preparation.

Although there was an occurrence of arrhythmia or weighting of the existing rhythm disturbances, sometimes fatal, pro-arrhythmic effect of the drug Cordarone® is mild, in comparison with most antiarrhythmic drugs, and usually manifests itself in the presence of factors that increase the duration of the QT interval, such as interaction with other drugs and / or impaired electrolyte content in the blood (see " Side effect "and" Interaction with other medicinal products "). Despite the ability of Cordarone® to increase the duration of the QT interval, it showed low activity with respect to provoking ventricular "pirouette" tachycardia.

Due to the fact that it is possible to develop very rare cases of interstitial pneumonitis after intravenous administration of Cordarone®, when there is an apparent shortness of breath or dry cough after its intravenous administration, either accompanied or not accompanied by deterioration of the general condition (increased fatigue, increased body temperature ) it is required to perform a chest X-ray and, if necessary, cancel the drug, since interstitial pneumonitis can lead to the development of pulmonary fibrosis.However, these phenomena are mainly reversible with the early withdrawal of Cordarone® with or without glucocorticosteroids. Clinical manifestations usually disappear within 3-4 weeks. Restoration of the radiographic picture and function of the lungs takes place more slowly (in a few months). After mechanical ventilation of the lungs (for example, when surgical interventions were administered), patients who received Cordarone® had rare cases of developing acute adult respiratory distress syndrome, sometimes with a fatal outcome (it is assumed that they can interact with high doses of oxygen in the respiratory mixture). section "Side effect"). Therefore, it is recommended to exercise strict control over the condition of such patients. It is recommended that the functional "liver" tests (monitoring the activity of "liver" transaminases) be carefully monitored before starting the Cordarone® preparation and regularly during the treatment with the drug. During the first 24 hours after intravenous administration of Cordarone®, an intravenous solution,can develop acute liver damage (including hepatocellular insufficiency or liver failure, sometimes fatal) and chronic liver damage. Therefore, treatment with Cordarone® should be stopped with an increase in the activity of "liver" transaminases, which is 3 times higher than the upper limit of the norm.

Before surgical intervention by an anesthesiologist, the patient should be informed that the patient is taking Cordarone®. Treatment with Cordarone® may increase the hemodynamic risk inherent in local or general anesthesia. In particular, this refers to its bradycardic and hypotensive effects, reduction in cardiac output and conduction disorders.

It is not recommended simultaneous use with beta-blockers; inhibiting heart rate blockers of "slow" calcium channels (verapamil and diltiazem); laxative, stimulating the intestinal peristalsis, which can cause the development of hypokalemia.

Violations of water-electrolyte balance, especially hypokalemia: it is important to take into account situations that may be accompanied by hypokalemia, as predisposing to pro-arrhythmic phenomena.Hypokalemia should be corrected before starting Cordarone®.

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

Side effects of the drug (see the section "Side effect") usually depend on the dose; therefore, care should be taken when determining the minimum effective maintenance dose to avoid or minimize the occurrence of unwanted effects.

The drug Cordarone® can cause thyroid dysfunction, especially in patients with thyroid dysfunction in their own or family history.

Therefore, in the case of a transition from intravenous administration of Cordarone® to Kardaron®, inside, both during treatment and several months after the end of treatment, a thorough clinical and laboratory control of thyroid function should be performed. If thyroid dysfunction is suspected, serum TSH concentration should be determined (using a supersensitive assay forTTG).

In children, the safety and efficacy of Cordarone® has not been studied. In the ampoules of the drug Cordarone®, a solution for intravenous administration, contains benzyl alcohol. It was reported on the development of newborns sudden asthma with a fatal outcome after intravenous administration of solutions containing benzyl alcohol. Symptoms of this complication are acute development of choking, lowering of arterial pressure, bradycardia and collapse.

Kordaron® contains in its composition iodine and therefore can disrupt the absorption of radioactive iodine, which can distort the results of thyroid radioisotope research, but its use does not affect the reliability of the determination of T3, T4 and TSH in blood plasma.

Effect on the ability to drive transp. cf. and fur:

Based on safety data, there is no evidence that amiodarone violates the ability to drive vehicles or engage in other potentially hazardous activities. However, as a precaution, patients with paroxysms of severe rhythm disturbances during the treatment with Cordarone® should preferably refrain from driving andemployment by potentially dangerous kinds of activity demanding the raised concentration of attention and speed of psychomotor reactions.

Form release / dosage:Solution for intravenous administration 50 mg / ml.

Packaging:To 3 ml in ampoules of colorless glass (type I). For 6 ampoules in a plastic loop cell packaging without coating (tray). 1 pallet together with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:2 years. Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014833 / 01

Date of registration:27.01.2009

The owner of the registration certificate:Sanofi-Aventis FranceSanofi-Aventis France France

Manufacturer: & nbsp

SANOFI WINTHROP INDUSTRIE France

Representation: & nbspSanofi Russia, JSCSanofi Russia, JSCRussia

Information update date: & nbsp04,12.2014

Illustrated instructions

Instructions

Cordarone® (Cordarone®)